[Senate Hearing 108-]
[From the U.S. Government Publishing Office]
DEPARTMENTS OF LABOR, HEALTH AND HUMAN SERVICES, EDUCATION, AND RELATED
AGENCIES APPROPRIATIONS FOR FISCAL YEAR 2005
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THURSDAY, APRIL 1, 2004
U.S. Senate,
Subcommittee of the Committee on Appropriations,
Washington, DC.
The subcommittee met at 9:30 a.m., in room SH-216, Hart
Senate Office Building, Hon. Arlen Specter (chairman)
presiding.
Present: Senators Specter, Cochran, Stevens, and Harkin.
DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
STATEMENT OF ELIAS A. ZERHOUNI, M.D., DIRECTOR
ACCOMPANIED BY:
RAYNARD KINGTON, M.D., Ph.D., DEPUTY DIRECTOR, OFFICE OF THE
DIRECTOR
WILLIAM R. BELDON, DEPUTY ASSISTANT SECRETARY FOR BUDGET
DUANE ALEXANDER, M.D., DIRECTOR, NATIONAL INSTITUTE OF CHILD
HEALTH AND HUMAN DEVELOPMENT
BARBARA ALVING, M.D., ACTING DIRECTOR, NATIONAL HEART, LUNG,
AND BLOOD INSTITUTE
JAMES F. BATTEY, JR., M.D., Ph.D., NATIONAL INSTITUTE ON
DEAFNESS AND OTHER COMMUNICATION DISORDERS
JEREMY M. BERG, DIRECTOR, NATIONAL INSTITUTE OF GENERAL MEDICAL
SCIENCES
FRANCIS S. COLLINS, M.D., Ph.D., DIRECTOR, NATIONAL HUMAN
GENOME RESEARCH INSTITUTE
ANTHONY S. FAUCI, M.D., DIRECTOR, NATIONAL INSTITUTE OF ALLERGY
AND INFECTIOUS DISEASES
PATRICIA A. GRADY, Ph.D., DIRECTOR, NATIONAL INSTITUTE OF
NURSING RESEARCH
RICHARD J. HODES, M.D., NATIONAL INSTITUTE OF AGING
SHARON H. HRYNKOW, ACTING DIRECTOR, FOGARTY INTERNATIONAL
CENTER
THOMAS R. INSEL, M.D., DIRECTOR, NATIONAL INSTITUTE OF MENTAL
HEALTH
STEPHEN I. KATZ, M.D., Ph.D., DIRECTOR, NATIONAL INSTITUTE OF
ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
STORY C. LANDIS, Ph.D., DIRECTOR, NATIONAL INSTITUTE OF
NEUROLOGICAL DISORDERS AND STROKE
TING-KAI LI, M.D., DIRECTOR, NATIONAL INSTITUTE OF ALCOHOL
ABUSE AND ALCOHOLISM
DONALD A.B. LINDBERG, M.D., DIRECTOR, NATIONAL LIBRARY OF
MEDICINE
KENNETH OLDEN, Ph.D., S.C.D., L.H.D., DIRECTOR, NATIONAL
INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
RODERIC I. PETTIGREW, Ph.D., M.D., DIRECTOR, NATIONAL INSTITUTE
OF BIOMEDICAL IMAGING AND BIOENGINEERING
JOHN RUFFIN, Ph.D., DIRECTOR, NATIONAL CENTER ON MINORITY
HEALTH AND HEALTH DISPARITIES
PAUL A. SIEVING, M.D., Ph.D., DIRECTOR, NATIONAL EYE INSTITUTE
ALLEN M. SPIEGEL, M.D., DIRECTOR, NATIONAL INSTITUTE OF
DIABETES AND DIGESTIVE AND KIDNEY DISEASES
STEPHEN E. STRAUS, M.D., NATIONAL CENTER FOR COMPLEMENTARY AND
ALTERNATIVE MEDICINE
LAWRENCE A. TABAK, D.D.S., Ph.D., NATIONAL INSTITUTE OF DENTAL
AND CRANIOFACIAL DISEASES
JUDITH L. VAITUKAITIS, M.D., DIRECTOR, NATIONAL CENTER FOR
RESEARCH RESOURCES
NORA D. VOLKOW, M.D., DIRECTOR, NATIONAL INSTITUTE ON DRUG
ABUSE
ANDREW C. VON ESCHENBACH, M.D., DIRECTOR, NATIONAL CANCER
INSTITUTE
JACK WHITESCARVER, Ph.D., DIRECTOR, OFFICE OF AIDS RESEARCH
OPENING STATEMENT OF SENATOR ARLEN SPECTER
Senator Specter. Good morning, ladies and gentlemen. The
time is precisely 9:30, which is our starting time, and the
Appropriations Subcommittee on Labor, Health, Human Services,
and Education will now proceed.
Today we will consider the appropriations process as it
applies to the National Institutes of Health. And as I have
stated on many occasions, I consider NIH the crown jewel of the
Federal Government. It may be the only jewel of the Federal
Government.
But medical science and humanity is deeply indebted to the
extraordinary work which has come out of medical research from
the National Institutes of Health.
The budget process is always complicated and a goal was
established to double NIH funding, which we have more than met.
When asked what would happen after doubling, as you know, my
response was instantaneous and obvious, and it was tripling. It
would be too hard to quadruple it before you triple it.
When I took over the chairmanship of this subcommittee in
January 1995, I took a look at the priorities and thought this
was none higher, really at the top of the list. And Senator
Harkin, the ranking member, agrees. We know around here if you
want to get something done, you have to cross party lines.
Sometimes it gets you into trouble if you have a primary
election campaign. My opponent thinks I should not talk to
Democrats. But Senator Harkin and I, when we have changed the
gavel, it has been seamless and we have proceeded to give
tremendous support to NIH.
We have a very tight discretionary budget this year. It is
up one-half of 1 percent, and that is very, very, very
difficult. The administration has put in a figure of $729
million over the $28.5 billion budget, and as I am sure you
know, we offered an amendment to increase it by $1.3 billion
and we were successful, 72 to 24.
But there were some strenuous arguments raised by my
colleagues in the Senate that NIH was getting too much funding
compared to other important research Departments in the Federal
Government. And when one of my colleagues made an impassioned
plea, I agreed with him that the other Departments were not
getting adequate funding. But that did not bear on not
adequately funding NIH. And what it takes is the subcommittee
chairmen to pick up those important research projects and take
the lead and get them funded.
We have a Federal budget of $2,400,000,000,000. Do you know
how much money that is? Well, nobody else does either.
They say if you took a room this size, it would be
insufficient to stuff $10,000 bills into it.
We can afford money for research. That is the best
investment that we are making beyond any question. But it is a
fight.
NIH has its own problems which you know about, challenges
on conflicts of interest, which we have addressed in a separate
hearing and we will talk about today, the issues about
compensation, an issue which I know is being addressed.
NIH is being attacked on an ideological level. The November
28, 2003 edition of Science had an editorial marked Don't Let
Ideology Trump Science. An amendment was offered in the House
of Representatives to strike four NIH grants because sex was
mentioned in the title, peer-reviewed. One of them involved a
question of spread of venereal disease at truck stops where
truckers are highly vulnerable, long stops, fatigue, away from
home, places frequented understandably by prostitutes, and NIH
wanted to make a study. And that and three other of your
projects were challenged because if you have sex in the title,
it makes a good 30-second commercial, if you voted for it, to
defeat you. The surprising thing was that in the House of
Representatives the amendment almost passed: 212 to 210.
Now, it just happens that the amendment was offered by the
fellow who wants to take my seat on the U.S. Senate who has
voted against every domestic spending bill, voted against Head
Start, voted against Medicare reform, voted against the budget
for Labor, Health and Human Services, voted against the budget
for NIH. So in this town you have to be prepared to defend
yourself against attacks. So if you have one or two, Dr.
Zerhouni, do not think you are being discriminated against.
It goes with the territory. I think it is within your pay
grade to defend yourself, Dr. Zerhouni, and to prevail, and I
think it is within my pay grade to prevail also. But it is a
battle.
So much for an opening statement. I read it just like Betty
Lou wrote it for me.
Super Senator Taylor. She is not just a regular Senator.
She is a super Senator.
Dr. Elias Adam Zerhouni began his tenure as the 15th
Director of NIH on May 20, 2000. He had a very distinguished
career prior to coming to NIH: executive vice dean of Johns
Hopkins University School of Medicine, Chair of the Department
of Radiology; Martin Donner Professor of Radiology; medical
degree from the University of Algiers School of Medicine; and
residency in diagnostic radiology at Johns Hopkins. Thank you
for joining us, Dr. Zerhouni, and we look forward to your
testimony.
SUMMARY STATEMENT OF DR. ELIAS ZERHOUNI
Dr. Zerhouni. Thank you, Mr. Chairman. It is our pleasure
to be here with the 27 institute and center directors of NIH to
present our budget, but also to express our thanks and
appreciation for your strong leadership on behalf of research
and medical research and NIH.
INTRODUCTION OF NEW INSTITUTE DIRECTORS
I would like to start by introducing three of our new
directors, and I will ask them to stand up to be introduced to
you, Mr. Chairman.
Dr. Story Landis is now the Director of the National
Institute of Neurological Diseases. She has been appointed in
the past year and has done an outstanding job already working
with all aspects of neurological disorders, including
collaboration with patient groups in trying to find the best
approaches to rising threats of neurological degenerative
diseases.
Dr. Nora Volkow is the new Director of the National
Institute of Drug Abuse. She has joined us from the Brookhaven
National Laboratory in Stony Brook University. She is a leader
in imaging of drug addiction and has already changed the
strategy of her institute in many appropriate ways.
Dr. Jeremy Berg is the new Director of the National
Institute of General Medical Sciences. Dr. Jeremy Berg joined
us from Johns Hopkins where he was the Chair of the Basic
Science Institute at Johns Hopkins and Chair of the Department
of Biophysics.
I also would like to mention two acting Directors, Dr.
Barbara Alving, who is the acting Director of NHLBI, and Dr.
Sharon Hrynkow, who is the acting Director of the Fogarty
International Center.
BREAKTHROUGHS AND ADVANCES
Mr. Chairman, members of the committee, it is my pleasure
to actually summarize the written testimony that we submitted
to you. What I would like to do is go right away and tell you
how important your investment has been in terms of specific
breakthroughs and advances between last year and this year.
NIH developed a completely new Ebola vaccine that can
protect the population in less than a month. This a real
breakthrough in biodefense.
Just 2 days ago, NIAID announced that a new SARS
experimental vaccine has been successful in animal experiments
and will enter human trials as soon as we can do so. This is
less than a year after the SARS epidemics which we knew not the
cause of and it took us several weeks to find the cause. A year
later, we are ready to fight this disease if it reappears.
We discovered in 2003 several genes, for the first time,
associated with schizophrenia. This was ranked as the number
two advanced scientific advance of 2003, following the
discovery of dark matter in the universe.
We identified just 3 weeks ago a new master switch gene
relating to type 2 diabetes. This is a very important discovery
that will help us in discovering how type 2 diabetes develops.
We have changed the practice paradigm of long-term hormone
replacement therapy for women because of the landmark studies
of the Women's Health Initiative.
Today on the cover of Nature magazine, we are announcing
the completion of the rat genome, a very important advance. As
you know, by 2005 we were hoping to only have the human genome
available to us. We now have the mouse, the rat, and the human
genome, and we will be able to do comparative analysis that
will advance our understanding of biology and disease.
NIH ROADMAP FOR MEDICAL RESEARCH
All throughout the past 2 years, we have also taken into
account the need for new science strategies, and this is what
we call the NIH roadmap for medical research. The roadmap is
essentially our effort to find ways to accelerate basic
research discoveries and speed the translation of those
discoveries into clinical practice. It is a dedicated effort to
explicitly address roadblocks that slow the pace of medical
research in improving the health of the American people.
The major driver for this approach is exemplified on this
slide in front of you, and that is that we need to transform
medical research in the 21st century. In the 20th century, we
treated disease when symptoms appeared and normal function had
been lost. Why was that? Because for the past 5,000 years and
the 20th century included, we did not understand the molecular
and cellular events that led to disease. So we had to wait
until the disease was explicit. And this is very expensive in
both financial and disability costs.
The paradigm of the 21st century is that we will intervene
before symptoms appear and preserve normal function for as long
as possible because we do understand much better the genetic
events that lead to disease.
We have come up with very bold initiatives. We will
integrate all clinical research networks that are under NIH
throughout the country and link them to community physicians to
form new communities of research that will translate much
quicker, much more efficiently than we have in the past the
benefits of our fundamental understanding of research.
A good example is juvenile rheumatic diseases, a disease
set that affects only 300,000 children in the country. To do
good research and have enough understanding of what happens, we
need to recruit patients across the Nation, and this will be
facilitated by a project of the roadmap called National
Clinical Research Networks with trained community physicians in
every community linked to academic centers.
We continue to invest across NIH in a combined and
coordinated fashion to advance medical research as fast as we
can. This year we are requesting $237 million for the roadmap.
STEWARDSHIP
We have continued also to focus on management excellence
and stewardship of our resources. Let me point out two very
simple statistics. Our funding went up by 141 percent in the
past 10 years, almost 2 and a half times, 2.4 times. Our FTE's,
the number of people, at NIH needed to manage this portfolio
has only increased by 16 percent. Why? Because we have
aggressively used modern methods of management using
information systems to prevent the need for us to increase our
FTE numbers. Our Research Management and Support budget has
gone from 4 percent of our budget to 3.5 percent of our budget.
So we are doing what you are asking us to do and being very
good stewards.
As you said, we will have on May 6 a final meeting of the
Advisory Committee to the Director to finalize the
recommendations of the Blue Ribbon Panel for conflict of
interest and will report back to you as soon as we have that.
FISCAL YEAR 2005 BUDGET REQUEST
Mr. Chairman, we are requesting a budget of $28.607 billion
which is $28.527 billion from this committee, and a 2.6 percent
increase over 2004. We also have at our program level $47
million for nuclear and radiological countermeasures which are
housed in the Public Health Service emergency fund.
PREPARED STATEMENT
We are pleased to be here and will answer any of your
questions. Again, we would like to thank the bipartisan support
of this committee over the years. Thank you, Mr. Chairman.
[The statements follow:]
Prepared Statement of Dr. Elias A. Zerhouni
Good morning, Mr. Chairman and members of the Committee. Let me
begin by expressing my deepest appreciation to the Congress, Secretary
Thompson, President Bush, and the American people for their generous
and bipartisan support of the NIH's efforts to help improve the health
of all our citizens. I respect the extraordinary effort of this
committee and, Mr. Chairman, your leadership as well. I thank you for
it.
The year 2004 marks a sea change for the NIH and its Roadmap for
Medical Research. We are refining our basic and clinical research
programs to ensure that new discoveries rapidly lead to new and
improved diagnostics, treatments and prevention strategies that extend
the length and improve the quality of human life.
In my testimony today, I want to cover four areas: first, highlight
several key research advances that took place in the last year which
represent the critical contributions of NIH intramural researchers and
grantees; second, give examples of how the NIH Roadmap effort will help
shape our approach to patient-oriented research; third, offer examples
of our stewardship; and fourth, present an overview of our budget. In
the course of my testimony, I will mention emerging priorities and our
plans for responding to the health challenges ahead.
BREAKTHROUGHS & ADVANCES
Each year, the public investment in research yields critical
scientific advances. The four I highlight here are just a sample of the
many that represent the development of new and improved treatments,
diagnostics, or prevention strategies that will affect the health of
the entire nation.
Few viruses are feared more than the Ebola, a deadly microbe that
causes outbreaks in Africa and Asia and kills up to 90 percent of those
it infects. Scientists at the NIH National Institute of Allergy and
Infectious Diseases Vaccine Research Center developed a single dose,
fast-acting, experimental Ebola vaccine that successfully protects
monkeys after just one month, and human trials are now under way.
This year NIH research further elucidated the role of widely used
hormone replacement therapies. The NIH halted the estrogen alone study
of the Women's Health Initiative on March 1, 2004 after 5.6 years of
follow-up, due to increased risk of stroke. You will recall that NIH,
in 2002, stopped the combination hormone trial arm of the Women's
Health Initiative early due to an increased risk of invasive breast
cancer, coronary heart disease, stroke, and pulmonary embolism in study
participants on estrogen plus progestin compared to women taking
placebo. It indicated that healthy postmenopausal women taking
combination hormone therapy also suffered twice the rate of dementia as
those taking a placebo. Together, the results of these clinical studies
changed conventional dogma, and provided important new evidenced-based
information to women who are deciding whether to begin or how long to
continue menopausal hormone therapy. These trials clearly are having a
major impact on the health of people we know and love--our wives, our
sisters, our daughters and our mothers.
The third advance was the discovery of genes associated with
schizophrenia, which is a profoundly disabling disorder that affects
one percent of the adult population. It is marked by hallucinations,
delusions, social withdrawal, flattened emotions, and loss of social
and personal care skills.
Research like this on the genetics of mental illness was named the
Number 2 scientific ``breakthrough of the year'' for 2003 by the
prestigious peer-reviewed journal, Science. Most of this work was
funded by NIH and included discoveries of candidate genes for
schizophrenia, depression, anxiety and bipolar disorders. These
discoveries bring us closer to developing new diagnostic tests,
strategies for prevention, and targets for the treatment of
schizophrenia and other mental disorders.
The fourth advance came only three weeks ago, when NIH announced a
major new discovery, the identification of a common variation of a
pancreatic ``master switch'' gene that increases the risk of type 2
diabetes by 30 percent. Type 2 diabetes now affects 17 million people
in the United States, and is responsible for enormous health care
costs. This gene discovery opens the door to the development of new and
more effective methods of prevention and treatment.
NIH ROADMAP
Let me now turn your attention to the NIH Roadmap for Medical
Research. I want to tell you why the Roadmap is so important to the
future of medical research and to innovations in improving people's
health. I also want to give you some examples of how we at NIH expect
the Roadmap to change the way we do research and the practice of
medicine.
One of the questions we face is how do we successfully do our part
in the battle to contain health costs? We need to address the following
issues: What are the roadblocks? What are the major challenges? How can
we most effectively invest the funds that the American taxpayers
entrust to us to fashion the fastest track to discovery as well as
translate those discoveries to the patient's bedside or the doctor's
office?
In seeking answers to these questions, one thing becomes clear. The
traditional paradigm of medical care--when practitioners waited for the
disease to cause the patient the loss of some function--must be
replaced by a paradigm where health professionals act before the
individual loses any function. This has become even more critical since
chronic diseases now consume about 75 percent of our fast-growing
health care expenditures.
Let me present four examples of how the NIH Roadmap will transform
our approach to biomedical research in specific disease areas.
The first example is schizophrenia, a disorder that--as I mentioned
earlier--affects one percent of the U.S. population. The peak onset
occurs between the ages of 18 and 25. Schizophrenia has the hallmarks
of both a neurodevelopmental and a neurodegenerative disease. But after
100 years of neuropathological study, we still lack knowledge of the
precise cause of the disorder.
Today, schizophrenia is the fifth leading cause of years lost due
to disability among Americans from ages 15-44. Although we can treat
the so-called ``positive'' symptoms, such as hallucinations and
delusions, we do not yet have treatments for the ``negative'' symptoms,
like withdrawal and cognitive deficits. And these are the largest
source of disability.
Less than 30 percent of people with this illness are currently
employed. And people with schizophrenia represent one of the largest
groups on atypical antipsychotics as the treatment of choice. In 2001,
Medicaid paid for more than 50 percent of the total spending on
atypical antipsychotics, amounting to $2.7 billion, a figure which has
been growing at roughly 25 percent a year for the past 3 years.
Today, we lack a diagnostic test or a strategy for preventing
schizophrenia. This situation is similar to cardiovascular disease 30
years ago in that we see schizophrenic patients only after their first
``heart attack,'' that is, episode, and we do not have the equivalent
of cholesterol as an identifiable risk factor.
However, what we have done recently--and what holds great promise
for those who are suffering--is identify 12 genes associated with risk.
Our challenge now is to move from the discovery of those genes--most of
which have no known function--to understand the role these genes play
in the onset and progression of this brain disease--and do something
about it.
Our hope is to use these genes to identify what is abnormal in the
brains of schizophrenics, identify it early and thus provide the
psychiatric equivalent of serum cholesterol. To accomplish this, we
must study the protein products of these genes by using molecular tools
that can make their function transparent.
It is precisely here that the NIH Roadmap will help accelerate the
effort to study protein products through so-called molecular
libraries--databases of information on small molecule compounds like
aspirin and antihistamines. These libraries will let researchers screen
hundreds of thousands of small molecules to yield these tools.
For example, we know that a variation in the neuregulin gene is
associated with an increased risk for schizophrenia. To understand how
this gene confers risk, we need to find chemicals that mimic or inhibit
the gene's function. This would give us a precise description of how
alterations in the gene change the activity of brain cells. Molecular
libraries will not only yield the tools to study the neuregulin gene
but also provide a test for vulnerability to schizophrenia. With such
tools and tests, doctors could approach risk for schizophrenia the way
we currently approach risk for heart disease.
A second example where the NIH Roadmap offers promise is in
pediatric diseases, through the creation of clinical research networks.
Uncommon disorders like the juvenile forms of rheumatic diseases,
such as arthritis, lupus and dermatomyositis, affect 300,000 children
in the United States. Not one of these diseases is common enough to be
studied intensively at any one academic health center. Thus, many such
centers as well as community-based pediatricians are needed to collect
a sufficient group of patients who can participate in these studies to
gather meaningful results.
The development of clinical research networks that focus on chronic
childhood diseases--like those already established for childhood
cancers--and the potential to include community physicians trained in
clinical research methodology in the research process will enable
clinical trials to be more efficient and effective.
Using the NIH Roadmap clinical research networks concept, this
could occur without building a new, and often very expensive,
infrastructure for every new trial. Including community-based
pediatricians as full partners in the research will allow us to
overcome some of the limitations of patient recruitment that we
currently experience and enable more children to participate in these
trials, and accelerate the development of new treatments.
The third example is Alzheimer's Disease (AD). We have made
considerable progress in understanding Alzheimer's Disease. Fifteen
years ago, we knew none of the genes that cause AD and we had only a
limited understanding of the biological pathways involved in the
development of brain pathology. Ten years ago, we could not model the
disease in animals. Five years ago, we were not funding any prevention
trials and had no way of identifying persons at high risk for the
disease. And, as recently as one year ago, we had no way of imaging
AD's characteristic amyloid plaques in a living person.
Today, we can do all of these things. And we are poised to make the
discoveries that will transform our understanding of the basic and
clinical aspects of AD and enable us to effectively prevent, diagnose,
and treat it using several NIH Roadmap initiatives.
Through basic research in Alzheimer's disease, we identified a
number of brain pathways that are potential targets for preventive
interventions. These range from dysfunction and death of specific
neurons to loss of the connections between neurons. Roadmap efforts to
improve imaging of small molecules will let us visualize the effects of
treatments more rapidly and accurately, which could make effective AD
clinical trials smaller, faster and more affordable.
My fourth and final example is cardiovascular disease. One of the
greatest public health success stories of the last half century is the
dramatic reductions in mortality from cardiovascular diseases. Studies
initiated by the NIH--the Framingham Heart Study and the Lipid Research
Clinics Coronary Primary Prevention Trial--have been key to that
success. They helped not only to identify risk factors that contribute
to the development of cardiovascular diseases, but also to demonstrate
the efficacy of therapeutic interventions to control them.
Even so, cardiovascular disease remains an enormous health burden,
accounting for 38 percent of all deaths in the United States in 2001.
Progress in reducing that burden will require continued efforts to
refine our understanding of risk factors, such as obesity and high
cholesterol, and to identify and evaluate new prevention approaches.
This means that large scale population-based studies will remain a
critical component of our research effort.
The NIH Roadmap will help fashion the interactive network and
involvement of many community-based practitioners. For example, we can
make better use of large-scale organizations set up for single studies,
such as the recently completed Antihypertensive and Lipid-Lowering
Treatment to Prevent Heart Attack Trial (ALLHAT). Instead of disbanding
it, we can involve many or all of the investigators in other trials
addressing not only cardiovascular disease but also other diseases. The
National Electronic Clinical Trials and Research (NECTAR) initiative--a
critical part of the Roadmap effort to re-engineer clinical research--
will enable data sharing and enhance comparison and aggregation of
results from multiple trials by using standard definitions of outcomes
and adverse events. In the future, patients will know directly from
their own community doctors, who will be equipped with the new web-
based NECTAR, what medical research can do for them in terms of
participation in studies, the best available therapies, and nearby
advanced research centers.
STEWARDSHIP
We realize that to advance the NIH scientific agenda, our
management and administration must be effective, efficient and
productive. By introducing new information technology and business
systems and streamlining governance structures, we are placing
continuous improvement of management and administrative functions at
the forefront of our agency priorities. Let me highlight a few of our
efforts.
NIH is making rapid progress to modernize its business and
financial systems. An agency-wide information technology system, known
as the New Business System (NBS), is integrating such processes as
acquisitions, travel, property, and financial management. This effort
will reduce the cost and complexity of doing business, enhance the
level of service, and improve management controls.
NIH is also improving its peer review system, which is recognized
as the cornerstone of NIH's success. The NIH Center for Scientific
Review (CSR), the focal point of the NIH peer review system, reviews
about 70 percent of the grant applications submitted to NIH. In fiscal
year 2003, CSR received a record-breaking 66,000 grant applications.
CSR is in the final stages of crafting new and more flexible review
panels organized into 24 scientifically-related clusters. NIH is also
incorporating new technologies into the review process through the
electronic Research Administration (eRA). The goal is to implement an
end-to-end electronic grants administration for NIH research award
mechanisms that could reduce the waiting period from submission of an
application to a grant award by more than two months--from 9 to 10
months down to 7 months.
Remarkably, because of improvements in productivity over the past
ten years, NIH funding has grown 141 percent, while our FTEs have
increased by only 16 percent.
The NIH also realizes the need for a more efficient means of trans-
NIH coordination. To streamline decision making, we reduced the
plethora of NIH administrative committees down to a trans-NIH Steering
Committee and 5 working groups. Additionally, as we discussed when I
met with the subcommittee in January, all our conflict of interest
policies and procedures are under review both to ensure that they meet
the highest standards and, most importantly, to preserve the public's
trust in the NIH. I will soon receive the report of a Blue Ribbon Panel
I created to advise NIH on what changes they think we should make. I
will inform you about their conclusions, and mine, once they complete
their work next month.
BUDGET
The discretionary fiscal year 2005 budget request for the NIH is
$28,607 million ($28,527 million from this subcommittee and $80 million
from the VA/HUD subcommittee), an increase of $729 million or 2.6
percent over the fiscal year 2004 Enacted Level. In addition, $47.4
million is included in the budget authority request of the Public
Health and Social Services Emergency Fund (PHSSEF), for NIH research in
radiological/nuclear countermeasures, and $150 million in mandatory
funds was previously appropriated for the Special Type 1 Diabetes
Initiative, bringing NIH's program level total to $28,805 million, or a
2.7 percent increase. The budget increases funding for the NIH Roadmap
(+$109 million), obesity research (+$40 million), which will thus grow
by 10 percent from $400 million in 2004, and biodefense research (+$74
million), an increase of 4.5 percent over fiscal year 2004.
CONCLUSION
In conclusion, I want to reemphasize the NIH commitment to help
improve the health of the American people. Although we have had great
success in changing acute lethal diseases like AIDS and many cancers
and childhood diseases into chronic manageable diseases, there are many
challenges ahead. Life expectancy has increased and the diseases of
aging and the aging population have become major priorities.
With a shift from acute to chronic diseases, health disparities and
pediatric diseases also present challenges, as do emerging and re-
emerging diseases, such as SARS. We are confident, as the committee has
shown it is, that medical research will make a critical difference in
the lives of all Americans.
As the NIH director, I fully understand and embrace my role as the
steward of our Nation's investment in medical discovery. And I remain
vigilant to ensure that these precious resources--including over
212,000 scientists working at 2,800 institutions in the United States
and overseas and the 5,000 scientists at the NIH itself--are used
wisely and efficiently and produce not only new knowledge but also
tangible benefits that touch the lives of every individual who reaches
out for our help.
BUILDINGS AND FACILITIES PROGRAM
Mr. Chairman and Members of the Committee: I am pleased to present
the President's budget request for the Buildings and Facilities (B&F)
Program for fiscal year 2005, a sum of $99,500,000.
ROLE IN THE RESEARCH MISSION
State-of-the-science research and support facilities are a vital
part of the research enterprise. The National Institutes of Health's
(NIH) Buildings and Facilities (B&F) program designs, constructs,
repairs and improves the agency's portfolio of laboratory, clinical,
animal, administrative and support facilities at its six installations
in three states. These facilities house researchers from the NIH
Institutes' and Centers' (ICs) intramural basic, translational, and
clinical research programs; the NIH leadership, and various programs
that support agency operations. The fiscal year 2005 B&F budget request
supports critically needed and timely investments to keep the agency's
facilities and supporting physical infrastructure healthy, safe,
secure, and research ready.
The B&F budget request is the product of a comprehensive, corporate
capital facilities planning process. This process begins with extensive
consultation across the research community and the NIH's professional
facilities staff. It works through the Facilities Working Group, an
advisory committee to the NIH Steering Committee and the HHS Capital
Investment Review Board. The budget request is the current year plan in
a rolling five-year facilities plan. Through this process, the real and
insistent program demand for more effective and efficient facilities
designed to support current and emerging investigative techniques,
technologies, and tools is integrated with, and balanced against, the
need to repair, renovate, and improve the existing building stock to
keep it in service and to optimize its utility.
The fiscal year 2005 request provides the necessary funding support
for the ongoing safety, renovation and repair, and related projects
that are vital to proper stewardship of the entire portfolio. It
provides funds to continue the functional integration of the clinical
research components of the existing Building 10 with the new Mark O.
Hatfield Clinical Research Center (CRC). Additionally, the request
includes funds to: complete the design of the Animal Research Center
(ARC) on the Bethesda campus; complete the creation of a security
buffer around the Rocky Mountain Laboratories (RML), in Hamilton, MT;
and to add another chiller to the NIH's Bethesda campus central utility
system that is needed to meet current and anticipated cooling demands.
The fiscal year 2005 B&F budget request is organized among five
broad Program Activities: Construction, Essential Safety and Regulatory
Compliance, Repairs and Improvements, Renovations, and Equipment/
Systems. The fiscal year 2005 request provides funds for specific
projects in each of the program areas. The projects and programs
enumerated are the end result of the aforementioned NIH facilities
planning process and are the NIH's capital facility priorities for
fiscal year 2005.
FISCAL YEAR 2005 BUDGET SUMMARY
The fiscal year 2005 budget request for Buildings and Facilities is
$99.5 million. The B&F request contains $16.5 million for Construction,
including $5 million to complete the design of an Animal Research
Center; $9.5 million to complete the creation of a security buffer
around the Rocky Mountain Laboratories (RML) in Hamilton, MT; and $2
million for concept development studies of projects proposed in the
facilities plan.
There is a total of $6 million for Essential Safety and Regulatory
Compliance programs composed of $0.5 million for the phased removal of
asbestos from NIH buildings; $2 million for the continuing upgrade of
fire and life safety deficiencies of NIH buildings; $1 million to
systematically remove existing barriers to persons with disabilities
from the interior of NIH buildings; $0.5 million to address indoor air
quality concerns and requirements at NIH facilities; and $2 million for
the continued support of the rehabilitation of animal research
facilities. In addition, the fiscal year 2005 request includes $59.2
million in Repairs and Improvements for the continuing program of
repairs, improvements, and maintenance that is the vital means of
maintaining the complex research facilities infrastructure of the NIH.
The request includes $10.8 million in Renovations to complete the
Building 10 Transition Program. Finally, the request includes $7
million in Equipment/Systems for the Chiller 27 project.
My colleagues and I will be happy to respond to any questions you
may have.
______
Prepared Statement of Dr. Paul A. Sieving
Mr. Chairman and Members of the Committee: I am pleased to present
the President's budget request for the National Eye Institute (NEI) for
fiscal year 2005. This budget includes $671.6 million, an increase of
$18.8 million over the fiscal year 2004 enacted level of $652.7 million
comparable for transfers proposed in the President's request. As the
Director of the NEI, it is my privilege to report on the progress
laboratory and clinical scientists are making in combating blindness
and visual impairment and about the unique opportunities that exist in
the field of vision research.
RETINAL DISEASES
Retinal diseases are a diverse set of sight-threatening conditions
that include age-related macular degeneration, diabetic retinopathy,
retinopathy of prematurity, retinitis pigmentosa, Usher's syndrome,
ocular albinism, retinal detachment, uveitis (inflammation), and cancer
(choroidal melanoma and retinoblastoma). One of the most tragic retinal
diseases, retinopathy of prematurity (ROP), causes severe vision loss
in premature, low-birthweight infants. ROP is characterized by
excessive growth of abnormal blood vessels in the back of the eye that
often hemorrhage and scar the retina. This year, results from an NEI-
funded clinical trial, called the Early Treatment of Retinopathy of
Prematurity (ETROP), established that early treatment, based on newly
developed diagnostic criteria, improves visual outcomes in infants at
the greatest risk of developing ROP. The ETROP study also found that
these new diagnostic criteria were helpful in select patient subgroups
that may not ultimately develop ROP. For these infants, careful
observation was found to be the best approach. Results from ETROP will
greatly improve visual outcomes for children with ROP.
Age-related macular degeneration (AMD) is a leading cause of
blindness in patients over age 60 in the United States and is a major
health problem in most other developed countries. More than 9 million
Americans have some degree of AMD (Archives of Ophthalmology, In
Press). Based on the results of an NEI-funded clinical trial, the Age-
Related Eye Diseases Study (AREDS), 1.3 million of these people would
develop advanced AMD if no treatment were given to reduce their risk.
If these people at risk for development of advanced AMD received the
supplements (vitamins C, E, beta-carotene, and zinc) used in AREDS,
more than 300,000 of them would avoid advanced AMD and any associated
vision loss over the next five years. Delaying the advance of a disease
in older-age populations is an essential strategy to reduce the burden
and incidence of disease.
Uveitis is an autoimmune inflammatory disease of the eye that
accounts for up to 10 percent of blindness in the United States
(Ophthalmology 2004; 111:491-500). In collaboration with researchers at
the National Cancer Institute, NEI intramural scientists have reported
promising results with the use of a monoclonal antibody (daclizumab) in
the long term treatment of patients with uveitis. This new therapy
seems to have many fewer side effects than existing immunosuppressive
therapies, leading to an improved quality of life. Planning is underway
to begin a Phase III study to evaluate the full potential of this
therapy.
CORNEAL DISEASES
The cornea is the transparent tissue at the front of the eye.
Corneal disease and injuries are the leading cause of visits to eyecare
clinicians, and are some of the most painful ocular disorders. In
addition, approximately 25 percent of Americans have a refractive error
known as myopia or nearsightedness that requires correction to achieve
sharp vision; many others are far-sighted or have astigmatism.
NEI intramural scientists found that serum albumin represents up to
13 percent of the total water-soluble protein of the mouse cornea.
Humans also have abundant serum albumin in the corneal stroma. Because
the serum albumin accumulates in the corneal stroma by diffusion from
the blood supply surrounding the cornea, it may provide an improved
route of drug delivery to the cornea. Conjugating serum albumin to the
drug of choice and injecting the conjugate into the blood stream will
not only direct the drug within the cornea, but extend its half-life
within this tissue. Future research will evaluate the usefulness of
serum albumin as a drug carrier to treat corneal disorders.
NEI intramural scientists recently identified an enzyme called CDK5
that regulates corneal epithelial cell adhesion and migration. Using a
model wound healing system, these researchers found that the rate of
wound closure was significantly retarded in cells with too much CDK5
and accelerated in cells in which the CDK5 was inactivated.
Continuation of this line of research may provide the means to promote
rapid healing of corneal tissues that have been damaged by disease or
injury.
CATARACT
Cataract, an opacity of the lens of the eye, interferes with vision
and is the leading cause of blindness in developing countries. In the
United States, cataract is also a major public health problem. The
economic burden of cataract will worsen significantly in coming decades
as the American population ages.
Age-related cataract formation is believed to result from the
complex effects of aging on normal physiological processes. It has long
been recognized that lens transparency is a function of a very high
concentration of soluble proteins, the crystallins, within the
specialized lens fiber cell. In the lens, a-crystallin has a dual
function: it accumulates in fiber cells in high concentrations to
produce the high refractive index needed for transparency, and it
functions as a molecular chaperone to protect against clouding of the
lens due to protein aggregation. For some time, scientists have
attempted to understand how a-crystallin can continue to perform its
chaperone functions over a range of stress conditions encountered by
the lens during a lifetime. New data suggest that under low stress, a-
crystallin is maintained in a multi-subunit complex. Under conditions
of high stress, a-crystallin breaks into smaller sub-units that can
protect the clarity of the lens from protein aggregation. It has been
hypothesized that this chaperone function decreases with age and leaves
the lens more vulnerable to stressful conditions. Improving our
understanding of this protective role of a-crystallin may one day lead
to the means to prevent cataract.
GLAUCOMA AND OPTIC NEUROPATHIES
Glaucoma is a group of eye disorders that share a distinct type of
optic nerve damage, which can lead to blindness. Elevated intraocular
pressure (IOP) is frequently, but not always, associated with glaucoma.
Glaucoma is a major public health problem and is a leading cause of
blindness in African Americans (Archives of Ophthalmology, In Press).
A hallmark of glaucoma is the death of retinal ganglion cells (RGC)
in the retina, which can lead to catastrophic vision loss. Previous NEI
studies have found evidence that elevated IOP deprives RGCs of brain-
derived neurotrophic factor (BDNF), an endogenous protein that is
crucial to RGC survival. Ocular injections of BDNF in rodent models of
glaucoma have improved RGC survival. However, due to the relatively
short half-life of this protein, the need for frequent ocular
injections would not bode well in treating a chronic disease like
glaucoma. To overcome this hurdle, NEI-supported researchers recently
used gene therapy in rodent models of glaucoma to transfect RGCs with
the gene that encodes BDNF, providing a lasting and direct supply of
this essential protein. Ongoing NEI-supported laboratory work is
evaluating whether gene therapy with BDNF provides long-term benefit
and whether gene delivery with other neurotrophic agents, alone or in
combination with BDNF, improves RGC survival.
STRABISMUS, AMBLYOPIA AND VISUAL PROCESSING
Developmental disorders such as strabismus (misalignment of the
eyes) and amblyopia (commonly known as ``lazy eye'') are among the most
common eye conditions that affect the vision of children. In addition,
more than three million Americans suffer from visual processing
disorders not correctable by glasses or contact lenses (Archives of
Ophthalmology 1990; 108:286-290).
Patching the stronger eye has been a mainstay of amblyopia therapy.
Unfortunately, there is no specific patching regimen that is widely
accepted for treating the disease. To address the clinical issue of the
optimal number of patching hours for moderate amblyopia, an NEI-
supported clinical trial compared daily patching of two hours versus
six hours for children with moderate amblyopia. Results from this
clinical trial revealed that patching the unaffected eye of children
with moderate amblyopia for only two hours daily is as effective as
patching the eye for six hours. This finding should improve treatment
compliance as patching can be a socially stigmatizing and uncomfortable
practice for young children.
TECHNOLOGICAL INNOVATIONS
The marriage of computer technology and medical science is creating
advances in treating even the most intractable diseases. In one such
union, specially designed computer chips implanted in the eye may one
day make it possible to partially restore visual function to the blind.
Ocular neuro-degenerative diseases such as retinitis pigmentosa (RP)
and macular degeneration damage and destroy the light-sensitive
photoreceptor cells in the retina. The microelectronic retinal
prosthesis, a device developed by NEI-supported researchers, mimics the
function of photoreceptor nerve cells by turning light into electric
signals. In a recently published study, a 74 year-old patient blind
with RP was able to see spots of light, detect motion, and recognize
simple shapes. Although preliminary, these results are a promising
first step in realizing a prosthetic device that can restore ambulatory
vision to patients with retinal degenerative diseases, which are a
major cause of vision loss in this country.
PROGRAM INITIATIVES
The rapid progress in areas of gene discovery and bioinformatics
has created the need for enhanced cooperation and coordination among
groups that provide genetic diagnostic information to the clinician and
patient, store and provide DNA specimens to researchers, and maintain
data banks of genotype-phenotype information. Such groups are
underrepresented in the area of human ocular disease. The purpose of
this initiative is to explore the establishment of a national central
registry and molecular database of securely coded information from a
large number of people with ocular diseases caused by genetic
mutations. Information will be provided through a network of
cooperating groups who provide genetic and diagnostic services to
patients and clinicians. Such a registry and database will be of great
value in advancing research for these important diseases.
Clinician scientists will play a major role in translating
laboratory findings into safe and effective therapies. However, the
vision research community has raised concerns about the future of
clinician scientists. Declining clinical revenues are making it
increasingly difficult for clinicians to find time away from the
examination room to get the training they need. However, many of the
investigational therapies now being contemplated will be translated by
the next generation of clinician scientists. We need to make sure that
current clinician scientists have a capable next generation to pass the
torch to.
In addition to its existing extramural training and career
development grant programs, the NEI is working to increase the ranks of
the clinician scientist through a new intramural clinician scientist
training program at the NEI. The Clinician Scientist Development
Program is designed for board eligible/certified clinicians who seek to
develop an independent research program that integrates the field of
vision research with the clinical study of patients with ocular disease
or disorders.
The NEI recently published its forward looking National Plan for
Eye and Vision Research. The NEI's ongoing planning process involves
the assessment of important areas of progress in eye and vision
research and the development of new goals and objectives that address
outstanding needs and opportunities for additional progress. The
National Plan can be accessed through the NEI website at: http://
www.nei.nih.gov/strategicplanning.
NIH ROADMAP
The NIH Roadmap provides a framework for the priorities the NIH as
a whole must address in order to optimize its entire research
portfolio. The NEI is committed to the initiatives of the Roadmap and
is working to meet its goals. I would like to highlight NEI's
involvement in two Roadmap Initiatives: ``Nanomedicine'' and ``Re-
Engineering the Clinical Research Enterprise.''
The NEI and the National Human Genome Research Institute are
heading an NIH committee charged with implementing the Nanomedicine
Roadmap Initiative. Nanotechnology originated in the fields of
engineering and physics and refers to the research and development of
materials and devices at the atomic, molecular or macromolecular
levels. Nanomedicine integrates nanotechnology with biomolecular
processes. The long-term goal of the Nanomedicine Roadmap Initiative is
the development of therapeutic nanotechnology interventions for medical
diagnosis and the treatment of disease. To meet these goals we are
establishing a process to solicit ideas and concepts germane to the
development of Nanomedicine Development Centers.
Nanomedicine Development Centers will be designed to achieve an
understanding of biological systems at the nanomolecular level.
Over the past decade NEI-supported laboratory research has given
rise to an unprecedented number of promising, pre-clinical therapies
for eye disease. NEI's continued success depends on building the
clinical infrastructure for translational medicine. Consonant with the
NIH Roadmap initiative ``Re-engineering the Clinical Research
Enterprise'' the NEI is creating cooperative clinical research groups
that will enhance and expand clinical trial infrastructure. Over the
last year, the NEI implemented the Diabetic Retinopathy Clinical
Research Network. More than 70 clinical centers with the capability to
participate in the clinical trials network have been identified. This
network joins the highly effective Pediatric Eye Disease Investigator
Group as models for future clinical networks the NEI plans to build.
Mr. Chairman that concludes my prepared statement. I would be
pleased to respond to any questions you or other members of the
committee may have.
______
Prepared Statement of Dr. John Ruffin
Mr. Chairman and Members of the Committee: I am pleased to present
the President's budget request for the National Center on Minority
Health and Health Disparities (NCMHD) for fiscal year 2005, a sum of
$196,780,000, which represents an increase of $5,324,000 over the
comparable fiscal year 2004 appropriation.
A STRATEGIC APPROACH TO ELIMINATE HEALTH DISPARITIES
Unprecedented scientific advances in biomedical research over the
last several decades dramatically improved public health. However,
racial and ethnic minorities and other populations that experience
disparities in health status have not benefitted equally from our
Nation's progress in scientific discovery.
The NIH supports a comprehensive research program to better
understand why a broad spectrum of diseases disproportionately impact
racial and ethnic minorities and the urban and rural poor. No other
scientific area so thoroughly transcends so many diverse areas of
science and involves all of the NIH Institutes and Centers (ICs).
The NCMHD plays a key role in framing the NIH health disparities
research agenda by conducting and supporting basic, clinical, social
sciences, and behavioral health disparities research; developing
research infrastructure and training programs; reaching out to and
disseminating health information to minority and other health disparity
populations; stimulating scientific programs within the NIH ICs to
uncover the causes of health disparities and eliminate their impact on
society; and developing and updating the NIH Health Disparities
Strategic Plan.
This past year, the NCMHD, in collaboration with the NIH Director,
every NIH IC, and the National Advisory Council on Minority Health and
Health Disparities, completed the first comprehensive NIH Health
Disparities Strategic Plan, based on scientific priorities and
opportunities that will lead to new therapies and prevention strategies
that will ultimately eliminate health disparities in America. This
evolving plan will guide future NIH health disparities research
efforts.
INNOVATIVE EFFORTS TO COMBAT HEALTH DISPARITIES
The NCMHD has accomplished much since its creation. Today, the
NCMHD has 60 Health Disparities Centers of Excellence spread across the
nation. These Centers of Excellence, now located in 23 states, the
District of Columbia, and Puerto Rico, support health disparities
research, research training, and community involvement to identify
factors that contribute to health disparities and to develop and
implement new diagnostic, treatment, and prevention strategies.
The NCMHD addresses the national need to develop a diverse, strong,
and a culturally competent scientific workforce by eliminating barriers
that prevent racial and ethnic minority students and students from
disadvantaged backgrounds from pursuing research careers. Currently,
the NCMHD supports about 300 researchers from 38 states through its two
Loan Repayment Programs, which help to level the playing field and make
it possible for under represented individuals to enter the scientific,
technological, and engineering workforce. These ``Health Disparities
Ambassadors'' are key to creating the culturally competent health
disparities and clinical research workforce of the future.
The NCMHD has also created a one-of-a-kind Research Endowment
Program. Unique at the NIH, this program addresses the national need to
build research and training capacity in institutions that make
significant investments in the education and training of minority and
disadvantaged individuals. This program is making it possible for 13
institutions located in 11 states and Puerto Rico to establish health
disparities endowed chairs and programs, enhance student recruitment
efforts, provide merit-based scholarships, recruit and retain faculty,
develop innovative instruction delivery systems in minority and health
disparities research areas, and access emerging technologies.
The NCMHD Research Infrastructure in Minority Institutions Program,
born out of a partnership between the National Center of Research
Resources and the Office of Research on Minority Health, (the
predecessor to the NCMHD) is making it possible for institutions to
target research efforts on health disparities that exist in the
Southwest Border States; in rural communities, such as the Appalachia
Region, the Mississippi Delta, and the Frontier States; and in urban
centers of the nation. Currently, 11 institutions in eight states
benefit from this program.
In addition to using its core programs, the NCMHD strategy to
eliminate health disparities also includes leveraging NIH dollars and
expertise by creating partnerships with the NIH ICs and other agencies
within the Department of Health and Human Services to fund health
disparities research, training, and outreach programs. Over the past
two years alone, the NCMHD forged many new partnerships, supporting
more than 400 research projects to combat health disparities in our
nation.
CLOSING THE HEALTH DISPARITY GAP
Racial and ethnic minorities and other health disparity populations
experience a disproportionate burden of illness, disability, and
premature death due to cancer, cardiovascular disease and stroke,
diabetes, HIV/AIDS, infectious diseases, infant mortality, and other
diseases. The Department of Health and Human Services, through its
``Closing the Gap Initiative,'' designates these areas as major
research priorities. NCMHD programs focus on these priorities and many
others. The following initiatives represent a small sampling of the
richness and diversity of NCMHD activities.
Cancer
Cancer deaths vary by gender, race, and ethnicity. Certain racial
and ethnic groups have lower survival rates than whites for most
cancers. Colorectal cancer rates among Alaska Natives are higher than
the national average and Asian Americans suffer disproportionately from
stomach and liver cancers. African American men have the highest rates
of colon, rectum, prostate, and lung cancers (Healthy People 2010).
NCMHD Health Disparities Centers of Excellence in 12 states across
the nation are bringing to bear their state-of-the-art research and
outreach programs to eliminate the impact of cancer on diverse
populations. These efforts take place in Alabama, Arizona, California,
Colorado, Georgia, Maryland, Mississippi, New York, Pennsylvania,
Tennessee, Texas, and Virginia. One example of this intense effort is
the American Indian and Alaska Native Health Disparities Center in
Colorado, which conducts cancer research to address the needs of Native
American and Alaska Native populations.
The NCMHD Research Infrastructure in Minority Institutions program,
which focuses on building research capacity at minority serving
institutions, also addresses cancer health disparities. The Charles R.
Drew University is working to improve the detection and
characterization of brain tumors, and researchers at San Francisco
University are examining the impact of social support, spirituality,
and depression on quality of life among breast cancer survivors from
diverse populations.
Forty-five Health Disparities Ambassadors supported by our Loan
Repayment programs have also set their sights on combating cancer
health disparities in 17 states including Alabama, California,
Colorado, Georgia, Illinois, Kansas, Massachusetts, Maryland, Michigan,
Minnesota, North Carolina, New York, Pennsylvania, Tennessee, Texas,
Virginia, Wisconsin, and in the District of Columbia. Some of the
exciting work taking place under this program includes a community-
based health promotion project to prevent cervical cancer in
Vietnamese-American women; research studies on racial differences and
barriers in obtaining breast, cervical, and colon cancer screening; and
a population-based study that examines the variation in outcomes of
colorectal cancer between African Americans and whites.
Collaboration with the other NIH Institutes and Centers has allowed
the NCMHD to extend the reach of its scientific expertise to tackle
cancer health disparities in rural populations. For example, the
Appalachia Cancer Network, cosponsored by the NCMHD and the National
Cancer Institute, addresses cancer in rural and medically underserved
Appalachian populations in West Virginia, Kentucky, Tennessee,
Virginia, Ohio, Pennsylvania, Maryland, and New York. The goal of this
network is to reduce cancer incidence and mortality and to prevent
future increases; to increase cancer survival; and to stimulate greater
coordination and participation among regional, state, and community
cancer control networks throughout Appalachia.
Cardiovascular Disease & Stroke
Cardiovascular disease takes a heavy toll on certain populations.
Heart disease rates have been consistently higher in the African
American population than in whites (Healthy People 2010). Data on
stroke risk factors are sparse for most racial and ethnic populations,
except for African Americans whose stroke deaths, when adjusted for
age, are almost 80 percent higher than in whites (Healthy People 2010).
Today, 13 NCMHD Health Disparities Centers of Excellence, located
in nine states across the nation including California, Georgia, Hawaii,
Maryland, Mississippi, North Carolina, New York, Pennsylvania, and
Texas focus on eliminating disparities due to cardiovascular disease.
Three Health Disparities Centers of Excellence in Georgia, Mississippi,
and New York focus on stroke research. The NCMHD also supports 20
Health Disparities Ambassadors spread across 11 states, including
California, Florida, Illinois, Indiana, Massachusetts, Michigan, New
Hampshire, New Jersey, New York, Ohio, and Texas, who have set their
sights on eliminating health disparities due to cardiovascular disease.
The NCMHD Health Disparities Center of Excellence at Jackson State
University in Jackson, Mississippi is built on a partnership with the
University of Mississippi Medical Center, the University of Pittsburgh,
and the Jackson Medical Mall Foundation. This Center's research agenda
focuses on cardiovascular disease, stroke, and cancer in the African
American population in Mississippi.
The NCMHD also partners with its fellow NIH ICs, in the battle
against cardiovascular disease and stroke disparities. The NCMHD
partners with the National Heart, Lung, and Blood Institute to support
the Jackson Heart Study. This study evaluates the environmental and
genetic factors contributing to the disproportionate incidence of
cardiovascular disease in African American men and women living in
Mississippi. To date, almost 5,000 participants have benefitted from
the program by visiting the clinic, with an average of 25 participants
per week.
The NCMHD and the National Institute of Neurological Disorders and
Stroke partner to support two Specialized Neuroscience Research
Programs at the Morehouse School of Medicine and at the University of
Texas at San Antonio. This funding allows institutions to develop
state-of-the-art neuroscience research programs; strengthen
collaborations and resource-sharing between minority medical and
graduate schools, community-based organizations, and leading
neuroscience laboratories; expand training opportunities for minority
students to access and prepare for careers in neuroscience research;
and build new stroke research capacity.
Diabetes
Certain communities, including Hispanics, American Indians, African
Americans, and certain Pacific Islanders and Asian populations, as well
as economically disadvantaged and older people suffer
disproportionately from diabetes (Healthy People 2010). Diabetes is the
target of 27 Health Disparities Centers of Excellence in 17 states
including Alabama, Arizona, California, Colorado, Georgia, Hawaii,
Illinois, New York, North Carolina, North Dakota, Maryland,
Mississippi, Oklahoma, Pennsylvania, South Carolina, Texas, and
Wisconsin, as well as the District of Columbia. These programs include
the University of Hawaii at Manoa, where efforts are underway to reduce
and eliminate the major complications of diabetes in Pacific Islanders.
The University of Pennsylvania is developing behavioral strategies for
reducing obesity, a major factor contributing to diabetes in Latino and
African American communities.
The NCMHD has also deployed 15 Health Disparities Ambassadors to 10
states, including Alabama, California, Florida, Georgia, Illinois,
Massachusetts, New Hampshire, New York, Texas, and Virginia in the
effort to eliminate diabetes-related health disparities. These
individuals are conducting several important projects including
reducing obesity in diabetic African American women in the state of
Georgia and conducting educational interventions to prevent type 2
diabetes in middle school children in Alabama. Under the NCMHD Research
Endowment program, Xavier University of Louisiana is increasing the
diabetes research capability of its College of Pharmacy, promoting
health disparities research, and increasing the pool of well educated
under represented minorities who pursue advanced education in
biomedical and behavioral research.
New NCMHD partnerships are also playing a significant role in
eliminating diabetes health disparities. The NCMHD and the Indian
Health Service recently formed a partnership to develop the Tribal
Epidemiology Centers Program to address and eliminate health
disparities, including diabetes disparities, experienced by American
Indians and Alaska Natives. Recent NCMHD support enabled the creation
of a new Northern Plains Tribal Epidemiology Center in Rapid City,
South Dakota, continued funding for the other six existing EpiCenters,
and the development of a summer training institute for Indian Health
professionals. The funding will assist the EpiCenters to carry out
their training program for local health staff, and expand their
outreach activities to include a community-based research training
program.
HIV/AIDS
The disproportionate impact of HIV/AIDS on certain populations
underscores the importance of sustained research and prevention
efforts. In 2002, the AIDS diagnosis rate among African Americans was
almost 11 times the rate among whites. African American women had a 23-
times greater diagnosis rate than white women. African American men had
almost a nine-times greater rate of AIDS diagnosis than white men.
(Centers for Disease Control and Prevention Division of HIV/AIDS
Prevention 2003). In 2000, the AIDS incidence among Hispanics was 22.5
per 100,000 population, more then three times the rate for whites
(Centers for Disease Control and Prevention Division of HIV/AIDS
Prevention 2002:1).
In its fight against HIV/AIDS health disparities, the NCMHD
partners with the Centers for Disease Control and Prevention to support
the Racial and Ethnic Approaches to Community Health (REACH) Program.
REACH serves African American, Asian American, Pacific Islander,
Hispanic American, American Indian, and Alaskan Native populations at
increased risk for HIV/AIDS, cardiovascular disease, breast and
cervical cancer, diabetes and infant mortality. REACH develops,
implements, and evaluates innovative community level intervention
demonstrations that could be effective in eliminating health
disparities by 2010.
With the Agency for Healthcare Research and Quality, the NCMHD
supports the EXCEED Program to examine the underlying causes and
contributing factors for racial and ethnic disparities in health care
and to identify and implement strategies for reducing and eliminating
those disparities. Under this initiative, the Medical University of
South Carolina is examining strategies to address HIV/AIDS disparities
in health status between African Americans and whites, and the Baylor
College of Medicine is assessing the extent to which problems in
doctor-patient communication contribute to racial and ethnic
disparities in health care use.
Infant Mortality
In recent years, infant mortality rates in the United States have
steadily declined; yet the rate of Sudden Infant Death Syndrome among
African Americans is still twice that of whites. African American women
continue to be three to four times more likely than white women to die
of pregnancy-related complications. Hispanic women are less likely than
whites to enter into early prenatal care. Fetal Alcohol Syndrome
disproportionately impacts American Indian, Alaska Native, and African
American babies. (Healthy People 2010).
The NCMHD has Health Disparities Centers of Excellence in six
states including Alabama, Florida, Georgia, Texas, Iowa, and Wisconsin
that focus their efforts to improve the health of mothers and their
infants. One of these, the ``Mexican-American Women's Health Project
Center'' at the University of Texas, El Paso, partners with established
Hispanic health disparities researchers at the University of Arizona.
Their research efforts focus on modifying behaviors of Mexican-American
women relating to alcohol use; maternal health and nutrition; smoking
cessation; and the pursuit of recommended Pap and HPV screening tests.
Another Center at the University of Northern Iowa focuses on maternal
and child health disparities to address the special health needs of
Iowa's minority groups, which include urban African Americans, members
of the Meskwaki Indian Tribe, rural families, growing populations of
Latino and East African immigrants, and refugees from Bosnia and the
former Soviet Union.
The NCMHD also supports six Health Disparities Ambassadors through
its Loan Repayment Programs, who are focusing their attention on infant
mortality health disparities. These efforts is take place in Florida,
Maryland, Michigan, Missouri, North Carolina, and Pennsylvania. Ongoing
efforts include evaluating the link between sexually transmitted
diseases and infant mortality; determining leading health indicators
for women and girls; and creating logic models for maternal, child, and
family health programs.
RURAL HEALTH
Another top priority of the NCMHD is improving rural health across
the nation. In pursuit of this goal, the NCMHD established an
innovative Health Disparities Center of Excellence partnership between
Clemson University and Voorhees College, a Historically Black
Institution in South Carolina. This partnership will build capacity for
research, training, and outreach to address health disparities in rural
Hispanic and African American communities in South Carolina. The
Tuskegee University and the University of Alabama, Tuscaloosa Health
Disparities Center of Excellence partnership, in conjunction with the
University of Alabama Institute for Rural Health Research and community
organizations, focuses on adult immunization, infant mortality, cancer,
and diabetes.
Over the past year, the NCMHD also created opportunities to include
the expertise of other NIH ICs in addressing the needs of rural
communities, forming 16 new rural health partnerships with the NCI,
NHLBI, NIAAA, NIDA, NIEHS, NIMH, and the NINR. Examples of these new
projects include the Appalachia Cancer Network; the Deep South Network
for Cancer Control; the Rural Caregiver Telehealth Intervention Trial;
and studies on the effects of alcohol and violence on rural women;
coronary artery disease in Alaska Natives; migrant worker health and
the environment; mental health treatment for rural Mexican Americans,
African Americans, women, and the poor; cardiovascular health training
and outreach in Latino communities; and substance abuse among Ojibwe
children and youth.
CONCLUSION
The diversity of the American population is one of the greatest
assets of the nation. One of the greatest challenges facing the nation
is reducing and eliminating the profound disparity in health status
that exists for many of its populations. Without decisive action now,
the health challenges of the 21st century will expand along with the
increasing number of racial and ethnic minorities, inhabitants of rural
areas, and low socioeconomic populations.
The NCMHD will continue to combat health disparities through our
flagship programs. We will explore new opportunities to support
academic development for the health disparity researchers of tomorrow.
We will seek to create innovative programs to serve as a bridge between
NCMHD capacity building programs and an investigator's first
independent research effort. Cognizant of the value of engaging
communities in the elimination of health disparities, we will lead
efforts to conduct effective community-based outreach and research to
our numerous constituents. We will continue our legacy of creating and
nurturing partnerships to further increase the reach of our activities
to eliminate health disparities and we will encourage our fellow NIH
ICs to join the core health disparities programs of the NCMHD. The NIH
Roadmap Initiative should also provide opportunities for the NCMHD
constituent populations and research community to participate in
interdisciplinary research, clinical research, and technology.
Our vision of the future is a collective one that is embodied in
the NIH Health Disparities Strategic Plan. With leadership, commitment,
and strong scientific partnerships the NIH can advance scientific
discovery to ensure the health of all Americans. Working together, we
can turn the vision of an America where all citizens have an equal
opportunity to live long, healthy, and productive lives into reality.
______
Prepared Statement of Dr. Judith L. Vaitukaitis
Mr. Chairman and Members of the Committee: I am pleased to present
the President's budget request for the National Center for Research
Resources (NCRR) for fiscal year 2005, a sum of $1,094,141,000,
including support for AIDS research, which reflects a net decrease of
$84,815,000 over the comparable fiscal year 2004 appropriation, due
entirely to the phasing out of extramural construction projects for
fiscal year 2005.
It is a pleasure once again to have the opportunity to present the
accomplishments of NCRR-supported investigators and the future
directions for NCRR programs. As a component of the National Institutes
of Health, NCRR enables all lines of health-related discovery by
supporting the creation and development of critical research resources
and technologies. Because significant discoveries can be made at a
variety of levels--from molecules to patients, or even patient
populations NCRR supports a wide range of research resources across
several disciplines. These resources include state-of-the-art clinical
research environments, such as the nationwide network of General
Clinical Research Centers. The GCRCs facilitate clinical research and
protect the safety of participants in research. Each year more than
10,500 NIH-supported investigators conduct nearly 8,000 research
projects at the GCRCs, predominantly through more than a half million
outpatient research visits.
NCRR also supports research resources that develop and enhance
scientific access to advanced technologies, nonhuman models for the
study of human diseases, and career development and training. Because
of its trans-NIH focus, NCRR is well-positioned to facilitate research
by promoting the sharing of research tools and technologies as well as
providing the tools for research collaborations so that research teams
may address more complex research problems.
TECHNOLOGY AND INSTRUMENTATION
NCRR strives to ensure that neither the lack of research resources
nor technology development becomes rate-limiting for research. Two
Nobel Prize winners in 2003 can vouch for the importance of having
ready access to NCRR-supported resources. Dr. Roderick MacKinnon of
Rockefeller University, co-recipient of the Nobel Prize in Chemistry,
was honored for his groundbreaking studies of the structures and
functions of ion channels, which control the movement of electrically
charged atoms across cell membranes. Ion channel malfunctions can
trigger a host of human disorders, including irregular heart rhythms
and seizure disorders. Dr. MacKinnon noted that his award-winning
discoveries depended on having access to the scientific expertise and
advanced research instrumentation available at NCRR-supported resources
that specialize in mass spectrometry and crystallography of complex
molecules.
The challenge for NCRR is to keep pace with the biomedical
community's changing needs for research tools and to ensure that
tomorrow's research queries have tomorrow's critical instrumentation
and technologies in hand. The research resources and tools needed for
scientific investigations change dramatically over time as more complex
research queries are posed and require new technologies. Many research
tools now considered critical to understanding the cause of disease and
protecting the health of Americans were unheard of just a few years
ago. For instance, the Magnetic Resonance Imagers, or MRIs, now found
in hospitals and medical centers across the country were rare and
experimental less than 20 years ago. Dr. Paul Lauterbur of the
University of Illinois, Urbana-Champaign, depended on NCRR for many of
his investigations into magnetic resonance imaging. Dr. Lauterbur was
co-recipient of the Nobel Prize in Physiology or Medicine for his
studies that led to the development of MRI. From 1990 to 2000, Dr.
Lauterbur headed an NCRR-funded magnetic resonance research center,
which helped to facilitate the evolution of MRI into the invaluable
diagnostic and clinical research tool that it is today.
CLINICAL RESEARCH RESOURCES
Just as NCRR technology and instrumentation resources laid the
foundation for critical discovery in the basic and applied sciences,
NCRR also catalyzes clinical and patient-oriented research through the
network of GCRCs. In addition, NCRR develops and supplies investigators
with clinical-grade biomaterials, such as vectors for gene therapy and
human pancreatic islets for transplantation into patients with type 1
diabetes.
Research on rare diseases is one area where the GCRCs are ideally
positioned to catalyze clinical research. Rare disease research is
challenging in part because few patients with a particular rare disease
can be recruited from any one clinical center. The nationally
distributed network of the GCRCs makes them well-suited for enabling
multicenter studies of rare conditions. Therefore, NCRR has partnered
with the NIH Office of Rare Diseases and other groups to launch a
network of Rare Diseases Clinical Research Centers. The network
provides researchers with access to sufficient numbers of affected
patients for statistically meaningful studies. The network also
facilitates collaborations among scientists from multiple disciplines
and institutions.
To ensure the safety of human subjects participating in clinical
research projects, clinical investigators must adhere to Federal, state
and local regulations, policies, and guidelines. Yet these necessary
responsibilities place heavy demands on the time of already-busy
clinician investigators. To address this issue, NCRR established a new
GCRC staff position known as the Research Subject Advocate (RSA). The
RSA assists GCRC investigators, nurses, and staff to underscore the
safe and ethical conduct of clinical studies and represents the
interests of research participants. NCRR plans to extend and strengthen
the role of RSA in an approach that complements that undertaken by the
host institution.
HEALTH DISPARITIES
NCRR also supports clinical research studies on health disparities,
or diseases that disproportionately affect racial and ethnic minority
populations. NCRR has joined with the National Institute of Mental
Health to establish three Comprehensive Centers on Health Disparities.
These Centers will further develop the capacity of Research Centers in
Minority Institutions' (RCMI) medical schools to conduct basic and
clinical research in type 2 diabetes and cardiovascular disease, both
of which disproportionately affect minority populations. The Centers
will provide support to further develop the requisite research
infrastructure, recruit magnet clinical investigators, recruit and
develop promising junior faculty, and facilitate substantial
collaboration between the RCMI grantee institutions and more research-
intensive universities. NCRR also supports a Stroke Prevention and
Intervention Research Program that focuses on minorities, as well as a
mentored clinical research career development program to provide
clinical research training for doctoral and postdoctoral candidates in
minority institutions.
BIOINFORMATICS AND COMPUTER NETWORKS
Whether studying clinical manifestations of disease or the basic
biology of cells and tissues, today's biomedical researchers generate
vast data sets. This data deluge has increased scientific demand for
access to scaleable computation and modern management tools. A related
and equally important trend is the fact that biomedical research
projects are becoming broader in scope. For example, neuroscientists
now want to correlate brain images with events at cellular and
molecular levels, including gene expression. These broad research
projects require large multidisciplinary teams, gathered from
scientists distributed across the country.
To meet the challenges associated with these trends, NCRR supports
the development of bioinformatics tools, including the software
programs or algorithms that help scientists manage and analyze their
data. NCRR also is instrumental in the creation of high-performance
computer networks that link laboratories throughout the United States.
A few years ago, NCRR joined with the National Science Foundation,
Internet2, and investigators from several universities to establish the
Biomedical Informatics Research Network (BIRN). The BIRN provides the
tools for researchers to pool their data and to use federated databases
so that they can oversee the integrity of their data, use
bioinformatics tools for data mining, and visualize their data. In
fiscal year 2004, NCRR began expanding the number of BIRN sites in
order to establish a national infrastructure of bioinformatics tools
and provide access to scaleable computing that, in turn, is linked to a
nationally distributed network of modern imaging capabilities for
studies of degenerative brain disorders.
Other components of the BIRN network will link underserved
institutions, such as doctoral degree-granting minority institutions
and institutions in states that have received limited NIH research
funding because they include very few research trained investigators,
otherwise known as Institutional Development Award (IDeA) states. The
networks will foster collaborative research and help investigators
create a virtual critical mass of investigators. The BIRN also will
foster collaborations across institutions located at remote sites. NCRR
plans to establish a network for institutions with medical schools that
are associated with NCRR's Research Centers in Minority Institutions
(RCMI) Program. This electronic network will facilitate their
participation in large clinical trials and other research studies and
help define the factors contributing to health disparities among
minority populations and ways to overcome those factors.
In concert with other NIH components, NCRR participates in many NIH
Roadmap initiatives for example, development of a National Electronic
Clinical Trials and Research (NECTAR) network, which will form the
backbone for all clinical research networks. An important component of
NECTAR will be the standardization of patient data collection and
storage procedures, which will facilitate data sharing by
investigators. NCRR also supports other trans NIH Roadmap initiatives,
including the National Centers for Biomedical Computing, Exploratory
Centers for Interdisciplinary Research, and National Technology Centers
for Networks and Pathways.
PROTEOMICS
The availability of complete genomes for a variety of organisms
provides an important first step in understanding many complicated
biological questions, including the molecular basis for disease. The
next step in this process will be to develop technologies to quantitate
spatiotemporal differences in the levels of gene expression, assess
post-translational modifications of proteins, and characterize protein-
protein interactions in both healthy and diseased cells.
NCRR will support the development of the necessary technology and
infrastructure to advance the science of proteomics. An advanced
proteomics center will focus on multiple technologies, including
techniques for protein purification, structural techniques, mass
spectrometry, and DNA microarray instrumentation along with the
necessary bioinformatics.
CONCLUSION
I have today noted two important trends in biomedical research the
rapid accumulation of data and the broadening scope of research
studies. To these, I must add a third trend namely, the increasingly
collaborative nature of biomedical science. Some of today's most
pressing questions in biomedical science are so complex, so
multifaceted, that they cannot be addressed by a single investigator or
even a single research laboratory. In many cases, teams of scientists
with diverse skills and backgrounds are needed to get the job done.
It is my belief that this emphasis on interdisciplinary
collaborations, as evidenced by the multiple NIH Roadmap initiatives
related to this area, will bring about unprecedented gains in
biomedical science, and ultimately lead to improved health of all U.S.
citizens. Finally, as the research paradigm evolves toward greater
complexity, the infrastructure required to support that research must
evolve too.
I will be happy to respond to any questions you may have.
______
Prepared Statement of Dr. Duane Alexander
Mr. Chairman and Members of the Committee: I am pleased to present
the fiscal year 2005 President's budget request for the National
Institute of Child Health and Human Development (NICHD). The fiscal
year 2005 budget includes $1,280.9 million, an increase of $39.1
million over the comparable fiscal year 2004 appropriation of $1,241.8
million.
The NIH Roadmap provides the schema to guide the NICHD in achieving
its programmatic and research goals.
Today I would like to share with you how the research supported by
this committee is improving the lives of children, mothers, adults and
families, and helping to reduce health disparities. The NICHD is
participating in the trans-NIH obesity initiative identifying how
primary care physicians can help children maintain a healthy weight.
ENCOURAGING HEALTHY BIRTH OUTCOMES
Preeclampsia is a condition that affects five out of every hundred
women who become pregnant. Preeclampsia can occur suddenly, and without
warning, causing women to develop dangerously high blood pressure. In
some cases, the condition may progress to eclampsia in which women
experience potentially fatal seizures. Infants born to mothers with
preeclampsia may be extremely small for their age or may be born
prematurely, putting them at risk for a variety of other birth
complications. Although a woman's high blood pressure and seizures can
be treated, the only cure for preeclampsia is delivery of the baby. In
a significant step toward treating preeclampsia, researchers have
identified substances in the blood that have the potential to predict
who will develop preeclampsia. This knowledge may help us treat women
before preeclampsia becomes a serious problem, for them and their
infant.
We have also intensified our research in the area of stillbirth, a
devastating occurrence that affects far too many families. Health care
providers use the term stillbirth to describe the loss of a fetus after
the 20th week of pregnancy. Stillbirth can occur before delivery or as
a result of complications during labor and delivery. In at least half
of all cases, researchers can find no cause for the pregnancy loss. We
hope to change that. The NICHD has established the Stillbirth
Collaborative Network, which consists of research centers in Texas,
Utah, Rhode Island, and Georgia. In each center, a team of specialists,
including obstetricians, nurses, statisticians, and even grief
counselors will seek to understand the causes of stillbirth and
eventually find ways to prevent these deaths.
One way to increase the chances of a healthy pregnancy and healthy
birth outcome is to avoid alcohol during pregnancy. Infants born to
mothers who drink heavily during pregnancy are known to be at risk for
mental retardation and birth defects. They are also at increased risk
for Sudden Infant Death Syndrome (SIDS). NICHD researchers have now
identified another reason that women should not consume alcohol during
pregnancy: exposure to alcohol before birth affects the developing
nervous system in the arms and legs.
Recently, scientists in NICHD's Maternal-Fetal Medicine Units
Network reported a breakthrough in reducing a major cause of infant
mortality and the subsequent long term health problems associated with
prematurity. The scientists, working collaboratively in 14 academic
health centers across the United States, demonstrated that progesterone
administered to women at risk for premature birth could significantly
reduce the likelihood of early delivery. This was a very significant
discovery and we were delighted that others recognized its importance.
A few weeks ago, Parade magazine identified this discovery as one of
the ten most significant health advances of the past year.
NEW FRAGILE X CENTERS TO DEVELOP TREATMENT OPTIONS
In 2003, the NICHD funded three new Fragile X research centers.
Teams of researchers at each of the centers located in North Carolina,
Texas, and Washington state are developing new ways to diagnose both
the mild and severe forms of the condition, as well as new treatments.
Fragile X syndrome is the most common genetically-inherited form of
mental retardation currently known. It occurs in 1 out of every 2,000
males and in 1 in 4,000 females. The syndrome is caused by a mutation
in a specific gene, known as FMR1, on the X chromosome. In its fully-
mutated form, the FMR1 gene interferes with normal development,
resulting in mental retardation. In a partially mutated form, the FMR1
gene can cause fragile X syndrome in the children of a parent who is a
carrier. Until recently, it was thought that carriers did not have any
symptoms. Researchers have learned that some people with a form of
fragile X have mild cognitive and emotional problems. In addition, some
female carriers are likely to undergo premature menopause. In older
male carriers, the fragile X is associated with a neurological
degenerative syndrome. Identifying a means to predict which carriers
will develop the symptoms could be a first step toward developing new
treatments for these often overlooked symptoms. The Fragile X Research
Centers are focusing their research on how the fragile X affects the
developing brain and nervous system, how the disorder progresses
throughout an individual's life span, and treatments that can improve
the behavior and mental functioning of people with fragile X syndrome.
IMPROVING TREATMENT FOR CRITICALLY ILL CHILDREN
Critical care medicine for children is an emerging field where, in
general, physicians continue to rely upon adult treatments that have
not yet been tested for effectiveness in a young population. To change
this situation, the NICHD will help establish a national pediatric
critical care research network to develop and evaluate treatments for
children with disabling conditions. The initiative will foster
collaborations among scientists in many different fields and will
support research such as the best approach to care for children with
brain injury, the most effective way to transition a critically ill
child from an acute care to a rehabilitation setting, and the care of
critically ill children in the event of a bioterrorism attack.
CUTTING OBESITY THROUGH RESEARCH AND PROGRAMS
The increase in overweight and obesity among adults and children is
a major public health concern. In fact, in a recent analysis of
international data, NICHD researchers documented that U.S. teenagers
were more overweight than youth in 14 other developed countries. Like
many other health conditions that affect adults, the antecedents of
adult obesity can be found in childhood. Young children who are
overweight are likely to be overweight as adults. There is no single
explanation for the increase in childhood overweight and there is no
single solution. However, we know we must devise successful
interventions that help children maintain a healthy weight. As part of
the trans-NIH initiative, the NICHD will lead a major effort to
determine whether a weight control program for children and youth led
by primary care physicians as part of a comprehensive community-based
effort can be successful. Currently, most weight management programs
are administered through specialty clinics. However, there is strong
evidence that an appropriate intervention by a physician can have a
significant impact on personal behaviors such as tobacco use. Effective
weight management programs in a primary care setting would be
accessible to large numbers of children and would minimize the
geographic, social, and economic barriers that commercial weight
management programs can impose.
We are also developing an exciting research-based program that
helps to teach young children the fundamentals of good nutrition and
physical activity as well as how to make sense of the messages that
appear in the media. Three years ago, this committee provided funds to
the NICHD and other health agencies to develop programs that encourage
young people to engage in healthy behaviors. In response to this
directive, the NICHD has developed ``Media Smart Youth,'' an after
school program for children between nine and 13 years of age. The
program focuses on good nutrition and physical activity. But it also
provides skills to young children to interpret the messages about food
and snacks they see on television, in magazines, and on the Internet.
As part of their activity, the children who take part in Media Smart
Youth develop messages about the importance of good nutrition and
physical activity for their peers. The program has been tested with
youth groups around the country. In fact, the children at P.S. 127 in
the Bronx who took part in this program developed a message about
physical activity for young people that appeared for 30 minutes on the
Panasonic ``jumbotron'' screen in Times Square.
HELPING YOUNG CHILDREN PREPARE FOR SCHOOL
The preschool years are crucial for learning language, social
skills, and developing the intellectual capabilities that set the stage
for later success in school. Yet, comparatively little is known about
how to help young children obtain the greatest benefit possible from
the preschool experience. In December 2003, NICHD joined with two other
HHS agencies and the Department of Education, and launched a five year
research initiative to find the best ways to help preschoolers at risk
for failure in school acquire the skills they need for school success.
The initiative provided $7.4 million in funding for the first year.
Eight projects were funded to test research-based approaches to
preschool curricula, Internet based approaches to training preschool
teachers, and the importance of parental involvement for preparing
children to enter school. Funds requested for fiscal year 2005 will
allow us to expand this effort by funding academic researchers and
small businesses to develop and produce more effective measurements of
outcomes from preschool interventions.
SIDS RESEARCH SUPPORTS PROGRAM OUTREACH
We have known for more than 10 years that placing infants on their
backs to sleep reduces their risk of Sudden Infant Death Syndrome
(SIDS). In fact, since the NICHD launched the Back to Sleep SIDS risk
reduction campaign in 1994, the rate of SIDS in the United States has
declined by more than 50 percent. The NICHD continues a vigorous
research program to learn more about the causes and prevention of SIDS.
For instance, a team of NICHD-funded researchers in Ohio recently
discovered that infants who were placed to sleep on their backs were
less likely to develop fevers, get stuffy noses or develop ear
infection. Ear infections alone cost the health care system an
estimated $5 billion a year. So this simple behavior of placing infants
on their backs to sleep not only saves lives, it can save the health
care system large sums money by reducing the use of antibiotics to
treat ear infections. We also learned that infants who are normally
placed to sleep on their backs are at greatly increased risk of SIDS
when they are occasionally placed to sleep on their stomachs. New
research on SIDS continues to shape our SIDS risk reduction outreach
campaign. More recently, a major focus of the campaign has been
reducing the risks of SIDS in African American communities.
SIDS rates for African American babies have declined significantly
since the NICHD initiated its Back to Sleep campaign ten years ago.
Yet, the SIDS rate for African American infants is more than twice that
of white infants. To address this health disparity, the NICHD joined
forces with three national African American organizations in a unique
collaboration to reduce the risks of SIDS in African American
communities. The Alpha Kappa Alpha Sorority, the National Coalition of
100 Black Women, and the Women in the NAACP, sponsored three regional
summit meetings to raise SIDS awareness and train community leaders to
be resources and spokespersons for SIDS risk reduction in their
communities. The summit meetings were held in Tuskegee Alabama, Detroit
Michigan, and Los Angeles California, and they helped build an
infrastructure to involve faith-based, community, and service
organizations in reducing the risks of SIDS and in promoting the health
of infants. In Detroit, for instance, the summit ended with a ``SIDS
Sunday,'' which was held at Hartford Memorial Baptist Church on the
Sunday following that summit. Afterwards, other churches across the
region held a ``SIDS Sunday,'' where pastors shared SIDS information
from their pulpits, in their church bulletins, and with nurses and care
givers in their childcare centers and nurseries. The successful
collaboration of researchers, government officials, and the community
will create a strong foundation for launching other interventions to
eliminate health disparities.
MOTHERS LEAVING WELFARE HAD NO EFFECT ON PRESCHOOLERS
A study that received much of its funding from the NICHD
demonstrated that when a mother leaves welfare to enter the labor
force, it does not seem to have any negative effects on preschoolers or
young adolescents. The study was undertaken in response to the Personal
Responsibility and Work Opportunity Reconciliation Act of 1996, which
mandated stricter welfare requirements for all welfare recipients. The
researchers theorize that the positive and negative effects of going
off welfare and getting a job may cancel each other out. For example,
the increase in family income that comes with leaving welfare thought
to relieve the stress on a family may make up for the decreased amount
of time that mothers spend with their young children. In addition,
mother's transition to work had a slightly positive effect on teens,
reducing the teens' levels of anxiety. Conversely, teens whose mothers
left the job market and went on welfare developed increased anxiety
levels.
MICROBICIDES THAT CAN PREVENT SEXUALLY TRANSMITTED INFECTIONS
The NICHD is funding a number of projects to develop microbicidal
compounds to prevent the spread of sexually transmitted infections and
HIV. These compounds not only have the potential to prevent the spread
of disease-causing bacteria and viruses, but may also be effective in
preventing pregnancy. One project is a large scale test of the
contraceptive effectiveness of Buffergel, a compound that kills the
microorganisms that cause sexually transmitted diseases, and shows
promise as a contraceptive. Another project is studying a microbicidal
spermicide, C31G. The compound's effectiveness will be compared to that
of a conventional spermicide preparation. Working with the National
Institute of Allergy and Infectious Diseases, the NICHD has funded a
new system to test the quality of potential microbicides to determine
if they warrant further testing in human beings.
SAFER DRUGS FOR USE WITH CHILDREN
In January 2002, President Bush signed into law the Best
Pharmaceuticals for Children Act (BPCA). The law recognizes that drugs
may have different effects in children than they do in adults, and
seeks testing for drugs given to children. For roughly 75 percent of
the drugs approved by the U.S. Food and Drug Administration (FDA) for
adults, there is inadequate information available to ensure the safety
and effectiveness of the drugs in children. Moreover, there is little
or no data to guide physicians in prescribing dosages of these drugs
for children. Working in close collaboration, the NICHD and the FDA, as
directed by the BPCA, identified several high priority drugs to be
tested. The NICHD is currently establishing partnerships with pediatric
drug study networks in other NIH Institutes to expedite the study of
other clinically important drugs.
Drugs prescribed to pregnant women are also a concern. Although
nearly two-thirds of all pregnant women take at least four to five
drugs during pregnancy and labor, the effects of these drugs on a
pregnant woman and her fetus remain largely unstudied. In addition,
little is known about how pregnancy-related changes in cardiac output,
blood volume, intestinal absorption, and kidney function may influence
drug absorption, distribution, utilization, and elimination. Therefore,
the NICHD will establish a new network of Obstetric-Fetal Pharmacology
Research Units that will allow investigators to conduct key
pharmacologic studies of drug disposition and effect during normal and
abnormal pregnancies.
NATIONAL CHILDREN'S STUDY
In a few short years, The National Children's Study has evolved
from a concept to an exciting research collaboration poised to answer
critical questions about child development. The fiscal year 2005 budget
request continues planning dollars for this important project, but does
not reflect funding to launch the study itself, since it is still being
developed. The National Children's Study plans to examine the effects
of environmental influences on the health and development of more than
100,000 children across the United States, following them from before
birth until age 21. The NICHD serves as the lead agency on this
ambitious project, working closely with the National Institute of
Environmental Health Sciences, the Centers for Disease Control and
Prevention, and the U.S. Environmental Protection Agency. The
collaboration involves government agencies, the research community,
industry, and community groups.
NIH ROADMAP AND CLINICAL RESEARCH
To ensure that the necessary clinical research workforce is
available to translate laboratory findings to improved treatments for
patients, the NIH Roadmap is strengthening several stages in the career
path for these researchers. One new program will provide clinical
research experience and didactic training during medical and dental
school. Another will train doctorate-level professionals in multi
disciplinary collaborative clinical research settings that reflect the
diversity of today's clinical research team. To attract community
practitioners to clinical research, the NIH plans to create a cadre of
National Clinical Research Associates, community practitioners trained
in clinical research who will refer patients to large clinical trials
to enhance patient recruitment and more rapidly test potential
therapies. The NIH is also identifying ways to improve peer review of
clinical research grant applications and to enhance promotion and
tenure policies in academia for clinical researchers.
______
Prepared Statement of Dr. Allen M. Spiegel
Mr. Chairman and Members of the Committee: I am pleased to present
the President's budget request for the National Institute of Diabetes
and Digestive and Kidney Diseases (NIDDK) for fiscal year 2005, a sum
of $1,876,196,000, which includes $150 million for the Special
Appropriation for Research on Type 1 Diabetes through Sec. 330B of the
Public Health Service Act. The NIDDK transfers some of these funds to
other institutes of the NIH and to the Centers for Disease Control and
Prevention (CDC). Adjusted for mandatory funds, this is an increase of
$54,956,000 over the fiscal year 2004 enacted level of $1,821,240,000
comparable for transfers proposed in the President's request.
HIGHLIGHTS OF PROGRAM ENHANCEMENTS
I appreciate the opportunity to testify on behalf of the NIDDK's
efforts to combat the wide range of debilitating, chronic health
problems within our research mission, many of which are caused directly
or indirectly by obesity. Last year, I reported the creation of an
NIDDK Office of Obesity Research to intensify the fight against this
major public health problem, which is harmful both in its own right and
as a driver of type 2 diabetes, especially in minorities and the young.
Obesity can also be a contributing factor to nonalcoholic fatty liver
disease, gallstones, end-stage kidney disease, and urinary
incontinence. According to the CDC, approximately 64 percent of adults
and 15 percent of children and teens are considered either overweight
or obese. Disturbingly, these rates reflect skyrocketing trends over
the past two decades. To accelerate research to combat this epidemic,
the NIH Director established the NIH Obesity Research Task Force in
April 2003, with co-chairmanship by the Directors of the NIDDK and the
National Heart, Lung, and Blood Institute (NHLBI). I am pleased to
report that the Task Force has completed a draft Strategic Plan for NIH
Obesity Research, with input from external scientific and lay experts.
This Plan is posted on a newly established Web site that will alert
investigators to NIH obesity research funding opportunities, and also
inform the public about NIH efforts. Both the Plan and the Web site are
dynamic, and will evolve with changes in science and public health
needs. Acting alone, the NIH cannot halt or reverse obesity; however,
by generating and disseminating new research knowledge, we can lend a
vital scientific dimension to what must truly be a multifaceted
national effort.
The Strategic Plan will contribute to the prevention and treatment
of obesity by bolstering research in three major avenues: (1)
behavioral and environmental approaches to modify lifestyle; (2)
pharmacologic, surgical, or other biological/medical approaches; and
(3) ways to break the link between obesity and its associated health
conditions, known as co-morbidities. Within the goals and strategies
outlined in the Plan, the NIDDK will have a major role in three trans-
NIH initiatives.
The first is an effort to combat pediatric obesity in site-specific
ways--both in primary-care settings, and in other community settings,
such as the home, day-care, pre-school, school, and other venues.
Researchers will explore effective methods for the primary prevention
of inappropriate weight gain among children and adolescents who are not
overweight; secondary approaches to prevent further weight gain among
those already overweight or obese; and tertiary efforts to prevent co-
morbidities. We will build on studies the NIDDK is already pursuing to
evaluate the effects of so-called ``natural experiments'' in which
States or localities are changing the food and lifestyle choices and
cues that students encounter in school settings. We will also build on
studies to determine the effects of modifying the home environment,
such as the influence of T.V.-watching on obesity, eating behavior, and
physical activity. Our children are precious, and we should do all we
can to spare them the serious health problems that can attend a
lifelong struggle with obesity.
A second trans-NIH initiative will focus on the neurobiological
basis of obesity, which includes the intricate brain-gut circuits that
signal hunger and fullness, and thus are crucial to maintaining the
body's energy balance between calories consumed as food and expended in
physical activity. I previously reported on several hormones that
mediate energy-related signals, such as leptin, adiponectin, and
ghrelin. By exploiting these and other findings through innovative
collaborations between biomedical and behavioral researchers, we will
delineate the many pathways that modulate the control of eating
behavior in humans.
In a third trans-NIH initiative, the NIDDK will take the leadership
role in creation of an Intramural Obesity Clinical Research Program to
capitalize on the unique, collaborative infrastructure of the NIH
Clinical Research Center. This Program will foster multidisciplinary
approaches to obesity research in areas such as metabolism,
endocrinology, nutrition, cardiovascular biology, liver and other
digestive diseases, genetics, and the behavioral sciences. A ``magnet''
approach will draw upon the extensive expertise and resources of the
NIH intramural program to frame state-of-the-art clinical investigative
strategies and harness emerging technologies.
In addition to these trans-NIH initiatives, the NIDDK will support
a range of research, including ancillary studies to maximize the
resources already invested in ongoing clinical trials. We will pursue
challenging questions about obesity. What factors control where fat is
deposited, and the relationship between its location and differences in
metabolism, fat-cell regeneration, cell signaling, and associated co-
morbidities of obesity? What is the relationship between obesity and
abnormal levels of circulating and stored lipids, which are a hallmark
of metabolic problems? Can we identify biomarkers of change brought on
by the obese state? What genetic abnormalities underlie the co-
morbidities of obesity? What steps can people take to achieve long-term
maintenance of weight loss?
As obesity is escalating in the United States, so is type 2
diabetes. New estimates from the CDC place the number of people with
diabetes at 18.2 million, and about 90-95 percent of them have this
form of the disease. Disturbingly, about 5.2 million of those affected
are unaware. Millions of adults also have a condition called ``pre-
diabetes,'' in which glucose levels are elevated, but not as high as in
full-blown diabetes. Because clinical trials have demonstrated that
lifestyle and medical interventions can significantly delay or prevent
disease onset in those at high risk, it is critical to identify these
individuals and underscore the preventive actions they can take. The
NIDDK is taking vigorous steps to foster the generation of new
laboratory tests to improve diabetes detection, as well as to promote
the development of more cost-effective strategies to pinpoint those at
risk who can benefit most from early intervention. We are also
supporting studies to translate important advances from clinical trials
in diabetes prevention and care into medical practice. For example, for
a low-income Latino population, we are supporting a clinical trial to
compare current translation efforts for type 2 diabetes prevention with
a method that incorporates culturally-sensitive strategies. We are also
studying an interactive video conferencing system to enable
communication between health professionals at a large medical center
and diabetes patients in a rural state, with limited access to health
care providers. Interventions that are successful in these trials could
pave the way to widespread use by communities throughout the country.
Once considered an ``adult-onset'' disease, type 2 diabetes is
being increasingly diagnosed in children and adolescents, especially in
minority populations. We are launching a multi-center, school-based
trial (STOPP-T2D) to find ways to prevent the development of risk
factors for type 2 diabetes in middle-school children. The trial will
include school-based programs targeting nutrition, physical activity,
and behavior modification. Another multicenter trial (Treatment Options
for Type 2 Diabetes in Adolescents and Youth TODAY) will seek the best
treatment strategies.
Diabetes can lead to serious complications, such as blindness,
irreversible kidney failure, lower limb amputation, and heart disease.
We have established an NIDDK Diabetes Complications Working Group,
which is charged with seamless integration of these activities across
the Institute. The NIDDK also recently convened an international group
of clinical and basic researchers to brainstorm research approaches to
the urologic complications of diabetes. Because complications can
affect many organs, we collaborate with other components of NIH and the
Department to benefit from their expertise. For example, studies have
shown that the process of new blood vessel formation, called
``angiogenesis''--traditionally studied in relation to cancer--is also
critically important to vascular changes in diabetes, such as the
dangerous proliferation of blood vessels in the eye that can lead to
blindness. Angiogenesis will be the central theme of a new research
collaboration involving multiple NIH institutes.
In an aggressive research program on type 1 diabetes, we have
established unique, innovative, and collaborative research groups,
clinical trial networks, and consortia, with an overarching group to
standardize and coordinate their efforts. We are also working to
overcome barriers that currently prevent widespread clinical research
on islet transplantation to restore normal insulin-producing capacity
to patients. In collaboration with the National Institute of Allergy
and Infectious Diseases (NIAID), we are establishing a national
consortium to step up progress toward general clinical applicability of
islet transplantation.
To spur research in digestive diseases, the NIDDK recently
established a new Liver Disease Branch within its Division of Digestive
Diseases and Nutrition. With expert external input, this Branch is now
spearheading the development of a Liver Disease Research Action Plan
under the auspices of the Digestive Diseases Interagency Coordinating
Committee. As requested by the Congress, the NIDDK is submitting a
report on actions taken by the NIH and other HHS components in response
to recommendations from a Consensus Conference on hepatitis C. In other
research, broad approaches are providing insights into the inflammatory
bowel diseases--Crohn's disease and ulcerative colitis. Fundamental
studies are shedding light on the development of pathways that control
gut motility; integration of pain, motility and behavioral neural
circuits; and gut inflammation.
For polycystic kidney disease (PKD), a research consortium has
established the value of Magnetic Resonance Imaging for measuring
kidney size. This advance portends dramatic improvements in assessing
disease progression--a critical step in developing and evaluating new
treatments. The HALT-PKD Network is testing a regimen designed to lower
blood pressure and slow disease progression--the first of several
clinical studies envisioned. A workshop on oxalosis and primary
hyperoxaluria--an inherited cause of kidney stone disease--has
identified future clinical research directions, which will apply
emerging knowledge about underlying metabolic and genetic
abnormalities. We have also launched or expanded initiatives on
interstitial cystitis, urinary incontinence, and urinary tract
infections, consistent with the scientific recommendations of the
Strategic Plan of the Bladder Progress Review Group. A recently formed
Interstitial Cystitis (IC) Epidemiology Task Force is guiding efforts
in that area, as described in a requested report to the Congress.
TRANSLATION RESEARCH AND ROADMAP EFFORTS
Underpinning our disease-focused programs is an emphasis on
``translation'' research, which benefits patients directly by bringing
the fruits of laboratory discoveries into the arena of clinical
research, and by propelling the positive results of clinical trials
into medical practice. In one promising pilot effort to speed the
development of therapies for type 1 diabetes, we are building on an
innovative mechanism established by the NCI called ``Rapid Access to
Intervention Development.'' We are also pursuing several translational
efforts related to the NIH Roadmap for Biomedical Research. These
include development of non-invasive methods for diagnosing and
monitoring the progression of diabetes, kidney and digestive diseases;
harnessing new technologies such as proteomics the study of proteins
and their functions; as well as studying stem cells during human
development and tissue repair. We are leading an NIH Roadmap initiative
in ``New Pathways to Discovery'' by enhancing metabolomics--the study
of networks within the cell, and constituents of the cell, such as
carbohydrates, lipids, and amino acids. We are also playing a major
role in Roadmap efforts to build ``Research Teams of the Future'' by
spurring interdisciplinary research training. These efforts can benefit
programs within the NIDDK mission by bridging scientific disciplines
and catalyzing partnerships, such as collaborations between biomedical
and behavioral researchers, which are so important to moving obesity
research forward.
Today, I have presented a cameo of our many and diverse research
efforts and plans. Our research momentum has never been greater, and
our commitment to improving health remains clear and strong.
______
Prepared Statement of Dr. Sharon H. Hrynkow
Mr. Chairman and Members of the Committee, I am pleased to present
the President's Budget for the Fogarty International Center for fiscal
year 2005, a sum of $67,182,000, which reflects an increase of
$1,838,000 over the comparable fiscal year 2004 appropriation.
I welcome this opportunity to relate Fogarty's progress over the
past year and proposed plans for fiscal year 2005. Programs at Fogarty,
developed with the support and guidance of the Administration and this
Committee, reflect our nation's enduring commitment to achieve ``a
healthy America, in a healthier world.'' These were the words of the
late Congressman John E. Fogarty, Chairman of the House Appropriations
Subcommittee from 1951 until 1967, and for whom the center is named. He
championed research as the one truly global effort in which all nations
can and will join as real partners.
The health challenges facing the United States are many. Among the
communicable diseases, AIDS and tuberculosis continue to challenge even
the most sophisticated public health interventions. SARS emerged in
Asia and washed upon our shores, as did West Nile Virus several years
ago. And the emergence of avian flu in Asia and the United States is a
compelling tale that is a harbinger of probable Asian flu pandemics yet
to come. All told, the infectious threats cost our economy dearly. And
as chronic disease such as cancer, cardiovascular disease, and mental
health disorders increase year after year in the United States and
world-wide, both treatment and prevention efforts must be applied.
These challenges are shared with communities around the world.
To address these challenges, Fogarty supports a broad range of
research and training programs, each designed to tackle particular
health problems shared by United States and foreign populations. Our
particular focus is on improving the capacity of communities in poor
settings to address health challenges. Accordingly, our emphasis has
been on working with scientists and health professionals in low- and
middle-income nations on shared health problems. Our programs identify
research opportunities best addressed through international
cooperation. Fogarty's efforts are multidisciplinary, embracing
clinical, epidemiological, basic biomedical and social science
research. They are multi-sectoral, closely coordinated with our sister
institutes at NIH, the Centers for Disease Control and Prevention, and
international organizations with health and development missions,
including The World Bank and the World Health Organization. Moreover,
the programs enhance foreign relations with governments and communities
alike, and advance the historic humanitarian role of our nation. And
importantly, our programs promote a global culture of science, founded
on equal partnerships between scientists working across borders, in a
culture of sharing of scientific information, peer review and sound
management policies. Fogarty supports over twenty research and training
programs in more than 100 countries, involving more than 5,000
scientists in the United States and abroad.
What follows is a selective summary of ongoing and planned Fogarty
activities to support NIH international objectives and realize
Congressman Fogarty's vision.
THE HIV/AIDS EMERGENCY
HIV/AIDS has exacted a profound human toll in the United States and
abroad, reversed gains in child survival in many nations, and
threatened the economic stability of emerging markets by reducing the
number of working men and women. Reducing the impact of HIV/AIDS in
resource-poor countries, which bear the disproportionate burden of this
disease, requires a strong national commitment on their part and
international research cooperation to develop effective prevention and
control strategies. The Fogarty AIDS International Training and
Research Program (AITRP), now in its 16th year of operation, has been a
major source of support for training a cadre of foreign medical
scientists from developing countries needed to combat the global HIV/
AIDS pandemic. Working through U.S. universities, Fogarty has supported
Masters level, Ph.D., and post-doctoral training for young scientists
in countries most affected by the pandemic. These scientists are
testing HIV/AIDS vaccines abroad, developing effective public health
strategies to reduce transmission, and acquiring new knowledge for
treatment for those already infected.
Through the Fogarty AIDS Program, nearly 2,000 foreign researchers
from over 100 countries have been trained in the United States, many at
senior levels, and over 50,000 have trained in cutting-edge laboratory
methodologies through workshops and courses conducted in those
countries where HIV/AIDS is most devastating. This large international
cadre of trained scientists has facilitated the implementation of new
programs such as the Pediatric AIDS Foundation Call-To-Action, the
President's initiative on prevention of maternal-to-infant transmission
of HIV, and the President's Emergency Plan for AIDS Relief (PEPFAR). In
addition, health scientists trained under the program have played vital
roles in helping approximately 20 countries receive awards from the
Global Fund for AIDS, TB and Malaria. As we work in partnership with
colleagues around the world, the benefits of the Fogarty AIDS program
accrue also in the United States. Interventions and strategies
developed and tested abroad may have direct relevance to communities in
the United States.
Among research accomplishments in the past fiscal year, scientists
at the University of North Carolina and the University of Malawi have
identified a new and effective means to minimize postpartum
transmission of HIV through implementation of an inexpensive two-drug
antiretroviral regimen. This is of significance because low-income
women in sub-Saharan Africa typically do not obtain medical attention
during pregnancy and are usually uninformed of their HIV status until
delivery. Effectively deployed, this intervention will mean that more
newborn infants will have a chance to grow to be healthy adults, even
where the lack of resources and other obstacles to extending medical
care limit prenatal care and interventions.
CHANGING MICROBIAL THREATS
HIV/AIDS is a cautionary example. The rapid emergence of new
pathogens and re-emergence of infectious disease, believed to have been
controlled or contained, presents a disturbing new chapter in the grim
evolutionary battle between humans and microbes. This is the result of
social and demographic trends, including increases in international
travel and trading across borders, and changes in the genetic structure
of microbes that increase virulence and transmission, and weaken the
efficacy of existing drugs. Among major disease pathogens, malaria has
resurged due to resistance of the parasite to available drugs and
resistance of mosquitoes to insecticides. Malaria accounts for an
estimated 2 million deaths per year with increasing mortality due to
drug resistance and HIV-contaminated blood transfusions related to
malaria-induced anemia.
Building on the success of the AIDS training program, Fogarty
launched in 1996 the International Training and Research in Emerging
Infectious Diseases, a training program which builds expertise in
microbiology, epidemiology, and laboratory methods as part of a broad
effort to combat new and emerging diseases worldwide. Today, that
program has been expanded to include other infectious diseases as the
Global Infectious Disease Research Training Program, linking U.S.
universities with counterparts around the world to advance research
projects (through 27 Fogarty awards) and, importantly, to build the
next generation of scientists able to combat emerging infections, such
as SARS and West Nile Virus. Through this program, Fogarty is helping
to address the infectious disease challenges of today while preparing
for new pathogens yet to emerge tomorrow, as surely they will.
A powerful new tool for malariologists and other infectious disease
researchers concerns the use of sophisticated mathematics to predict
the course of an epidemic. Such mathematics, sometimes termed models,
can be used to chart the benefits of prevention and control measures.
Most recently, mathematical models were used to project the course of
the SARS epidemic in Asia, and to develop strategies to limit the
spread of the disease. Several years ago, Fogarty established a unit at
NIH concerned with the use of mathematical models for control and
prevention of several diseases, including malaria. The elements of a
malaria prevention program include reducing the population of
mosquitoes, treatment of malaria patients, and use of personal
protection such as bed nets to prevent mosquito bites. In addition,
there is a major effort underway to develop a malaria vaccine. The
Fogarty epidemiologists have used mathematical models to determine the
best strategy to employ such a vaccine, when it becomes available,
along with existing methods of malaria control and prevention. All this
must be done within the various complex ecological settings in which
malaria occurs. The use of such advanced mathematics in devising the
most effective strategies in the study of infectious diseases will
surely bring unexpected benefits to human kind. Importantly, through a
network of in-house research experts and extramural scientists, Fogarty
also employs mathematical models to assist biomedical research and
public health policy-makers prepare for and respond to bioterrorism
events. In coordination with DHHS, Fogarty has mobilized experts in
epidemiology, terrorism-response and public health policy in the
context of category A agents including plague, tularemia smallpox and
anthrax.
THE EMERGING EPIDEMICS OF CHRONIC DISEASE
By the year 2020, chronic disease is expected to contribute 60
percent of the global disease burden. The toll in the United States is
already enormous: for example, obesity has more than doubled from 15
percent during 1976-1980 to 31 percent in 1999-2000, and 65 percent of
adults ages 20 to 74 were overweight to obese in 1999-2000. As
populations age, and risk exposures shift due to environmental and
dietary factors, non-communicable diseases are estimated to become a
leading source of disability and premature death in developing nations
as well. Tobacco-caused disease and death is a major concern in the
United States and globally. In the United States, while picking up the
habit of smoking is on the decline in most groups, in young girls it is
on the rise (The World Bank). In low- and middle-income nations, as
wealth increases in urban settings, smoking commencement in youth, and
particularly in girls, is rising at alarming rates (The World Bank). To
address this challenge, Fogarty launched in 2002 its International
Tobacco and Health Research and Capacity Building Program. While in its
early stages, our expectation is that research will lead to new
interventions that will benefit U.S. communities as well as those
around the world.
There is a growing awareness of the burden on health inflicted by
trauma and injury both in the United States and worldwide. The numbers
are startling: more than 1.2 million people are killed in traffic
accidents annually, and millions more are injured or disabled. Deaths
from all types of injuries, including war and domestic violence, are
projected to rise from 5.1 million in 1990 to 8.4 million in 2020, with
road traffic injuries as a major cause for this increase, with millions
more sustaining injury that results in life-long disability. In
response to the growing epidemic of trauma, Fogarty is initiating a new
research and training program. Among the features of the program will
be training across the range of basic to applied sciences, the
epidemiology of risk factors, acute care and survival, rehabilitation,
and the long-term mental health consequences. Possible research areas
will include development of low-cost synthetic blood products and
diagnostic imaging tools, identification of behavioral intervention
strategies, particularly in youth and other high-risk groups, and
health services research to determine cost-effective measures for
emergency care in low-income settings. The new knowledge from the
program will benefit not only developing countries but, as low-cost and
effective strategies are identified, communities in the United States.
PREPARING THE NEXT GENERATION OF U.S. GLOBAL HEALTH LEADERSHI
While Fogarty works to build capacity and train young scientists in
the developing world, critical steps have been taken to ensure that
U.S. investigators at a formative stage in their careers also have
opportunities to engage in international research projects. The Center
will enhance and expand two programs to bring the next generation of
U.S. scientists more fully into the global culture of science. The
first of these, the International Research Scientist Development Award
(IRSDA) program, provides post-doctoral training for four years, two of
which must be spent conducting research in a developing country. Nearly
20 U.S. scientists are now being supported as IRSDA trainees.
Addressing an earlier step in the career path, Fogarty has recently
teamed with the Ellison Medical Foundation to create a second program,
the new pre-doctoral clinical research training program for U.S.
medical and public health students. Under this program, students will
spend a year in a developing country conducting NIH-sponsored clinical
research under the mentorship of an experienced foreign investigator
and a collaborating research team. The first students to be selected
will begin the program this summer.
ENHANCING OPPORTUNITIES FOR WOMEN IN SCIENCE
NIH's goal to bolster the nation's intellectual capital includes
attracting more women to careers in science, both to build a new
generation of talented scientists and to ensure that research issues
germane to women's health are addressed. Fogarty has extended this
important goal to international programs. At an October 2003 colloquium
on career path issues facing women in the life sciences, including
women in the developing world, Fogarty and its co-sponsors, the NIH
Office of Research on Women's Health and the National Institute of
Environmental Health Sciences, invited perspectives on opportunities in
advancing career issues for women in the life sciences from a community
of scientists, administrators and science funding agencies. To follow
up on the recommendations, Fogarty and its partners have agreed to:
collect data on developing country women in science and their career
paths; support workshops to develop skill sets for women scientists in
the developing world that will better enable them to take on leadership
roles within health research and/or policy settings; and develop and
implement strategies to effectively use the Internet and other
information technologies to support networking and mentorship.
ADVANCING THE NIH ROADMAP: GLOBAL POSITIONING
Fogarty supports programs linked to each of the three main Roadmap
themes--New Pathways to Discovery, Research Teams of the Future, and
Re-Engineering the Clinical Research Enterprise. In particular, to
improve the clinical research enterprise, Fogarty supports two new
programs aimed at training developing country professionals in
clinical, operational and health services research. These programs
represent a new approach to enhance clinical research, and pave the way
for new partners, namely those in low- and middle-income nations, to
work more closely on mental health, and on AIDS and TB with U.S.
counterparts. In support of Roadmap themes of new approaches and new
pathways to discovery, Fogarty is also supporting studies to identify
the impact of environmental degradation on economic development and
human health. These programs link social scientists, including
mathematicians and economists, with clinicians and medical researchers
to provide new insights and strategies to tackle urgent global health
challenges.
CONCLUSION
Mr. Chairman, global challenges require a global response.
Collective action is not only an economically rational approach to
global health research challenges, but a scientific and humanitarian
imperative. With the continued support of this Committee, Fogarty will
accelerate both research discoveries and applications through
international cooperative action to the benefit of the United States
and to global communities. ``A healthy America in a healthier world''
has never been as important as it is today. Thank you.
______
Prepared Statement of Dr. Roderic I. Pettigrew
Mr. Chairman and Members of the Committee: I am pleased to present
the President's budget request for the National Institute of Biomedical
Imaging and Bioengineering (NIBIB) of the National Institutes of Health
(NIH). The fiscal year 2005 budget includes $297,647,000, an increase
of $8,817,000 over the fiscal year 2004 enacted level of $288,830,000
over the comparable fiscal year 2004 appropriation.
The NIBIB's mission is to improve human health by leading the
development and accelerating the application of biomedical
technologies. The Institute is committed to integrating the physical
and engineering sciences with the life sciences to advance basic
research and health care. Our vision is to profoundly change healthcare
by pushing the frontiers of technology to make the possible a reality.
PROGRESS TOWARDS SUCCESS
Established by law in December 2000, the NIBIB has already
demonstrated an impressive track record as a conscientious steward of
public funds and has achieved significant milestones. In fiscal year
2003 the NIBIB funded approximately 750 awards, including 300 new
awards that received outstanding scores in a highly competitive peer
review system. Consistent with our mission, approximately one-third of
our new awards were for innovative, high-impact, though high-risk,
exploratory studies. These studies addressed the feasibility of a novel
avenue of investigation and/or breakthroughs in biomedical imaging and
bioengineering within a specific area. The Institute has also been
effective at reaching segments of the scientific community that
traditionally have not been supported by the NIH, especially those from
the engineering and quantitative sciences. Between the first and second
years of our grant-making authority, proposals to the NIBIB from first-
time NIH applicants increased significantly. In fiscal year 2003,
approximately 50 percent of respondents to requests for targeted
applications identified themselves as first-time NIH applicants.
The Institute has built a solid research infrastructure through the
issuance of numerous basic and applied research solicitations in
promising areas of scientific investigation. Responses to the
Institute's targeted initiatives far exceeded even the most optimistic
estimates based on prior NIH experience. Coupling this to the
successful outreach to new applicants and to the science community, it
is clear that NIBIB is filling an important need with regard to
catalyzing interdisciplinary science and supporting engineering
research aimed at translating scientific discoveries to practical
applications.
The NIBIB continues to foster successful linkages and
collaborations with other NIH Institutes and Centers, Federal agencies,
academic institutions, and private industry. We regard input from
industry as critical for helping to identify research needs that will
result in significant healthcare improvements as well as for
translating technologies and research results to patient applications.
As a first step in establishing collaboration with the biomedical
industry, the NIBIB sponsored a workshop on ``Biomedical Industry
Research and Training Opportunities'' in December 2003. Recommendations
from this meeting will be considered in the planning and development of
future NIBIB programs.
ADVANCING TOMORROW'S TECHNOLOGIES TODAY
Biomedical imaging and bioengineering are interdisciplinary fields
requiring collaborations not only among imagers and engineers, but also
with biologists, chemists, mathematicians, computer scientists, and
clinicians of all specialties. Today, the imaging and engineering
sciences are essential for improved understanding of biological
systems, detecting and treating disease, and improving human health.
Recent advances in these fields have enabled the diagnosis and
treatment of various diseases using increasingly less invasive
procedures. Benefits associated with minimally invasive imaging
applications include quicker and more accurate diagnoses leading to
improved patient outcomes at reduced costs. Minimally invasive image-
guided interventions now serve as powerful tools in the operating room
and can be applied to surgical procedures in urology, oncology,
neurosurgery, ophthalmology, orthopedics, and cardiology.
The quest for faster and more effective minimally invasive surgical
interventions has resulted in the introduction of computer-assisted
robotic technology, whereby the surgeon works with small tools through
small incisions. However, current instrumentation prohibits the surgeon
from actually feeling the forces exerted when manipulating tissue. This
lack of sensory control can be particularly detrimental in surgery,
where the forces applied to sutures are critical in creating knots that
are strong enough to hold, but do not damage the tissue. To overcome
this problem, NIBIB investigators are developing instruments with
three-dimensional sensors designed to give the surgeon a feeling
comparable to that of performing the task manually. This research has
additional applications as well, including expert-assisted surgery in
remote locations.
Magnetic resonance imaging (MRI) has been used successfully for
over 15 years to generate soft tissue images of the human body.
However, a number of diagnostic MRI applications require further
improvements in both imaging speed and spatial resolution. For example,
accurate abdominal imaging generally requires a complete image obtained
during a single ``breath-hold'' period, which can take up to 30
seconds. Many patients, especially those with respiratory illnesses,
cannot tolerate long breatholds. The NIBIB supports an active research
program on optimizing MRI speed and spatial resolution. One new
approach under study, called parallel imaging, collects MRI signals
from a number of independent coil shaped antennas. The appropriate
combination of these signals can provide an order of magnitude
improvement in imaging speed or resolution. Enhancements such as this
hold promise for greatly enhancing the non-invasive diagnosis and
treatment of abdominal and neurological diseases.
Functional magnetic resonance imaging (fMRI) is a relatively new
technique that builds on the basic properties of MRI to measure quick
and tiny blood flow related metabolic changes that take place in the
active brain. Thus, fMRI studies are capable of providing not only an
anatomical view of the brain, but a minute-to-minute recording of
actual brain activity. This technology is now being used by NIBIB
researchers to precisely map functional areas of the normal, diseased,
and injured brain and to assess risks associated with surgery or other
invasive treatments. Functional MRI can help physicians determine
exactly which parts of the brain are responsible for specific crucial
functions such as thought, speech, movement, and sensation. This
information allows physicians to better plan surgeries and radiation
therapies and to guide interventional strategies for a variety of brain
disorders.
Molecular imaging provides a way to monitor cellular activities in
normal and diseased states. The development of novel imaging
technologies, combined with new or enhanced probes that bind to and
``highlight'' defined cellular targets, will allow this technique to be
more broadly applied to biomolecules that are known indicators of a
diseased state. For example, NIBIB researchers have developed nanometer
sized fluorescent crystals, called quantum dots, that glow and can act
as markers for specific cells when bound to certain targeting agents
such as cancer cell antibodies. These agents can more precisely
pinpoint the location of the sentinel lymph node in breast cancer
patients. The sentinel node (SN) is the first node in the body to come
into contact with cancer cells as they leave the breast and begin to
spread to the rest of the body. Testing for metastatic cancer cells in
the SN allows for accurate staging using information from a single
lymph node, rather than 10 to 15 axillary nodes, and allows patients to
avoid many of the complications and side effects associated with a
traditional axillary lymph node dissection.
Advances in bioinformatics have been identified as having great
potential for positively impacting medical science and health care.
NIBIB researchers are developing and evaluating several innovative
technologies designed to help solve the information management problems
faced by today's doctors. Concepts enveloped in this system include a
medical record architecture designed for portability; a mechanism for
linking laboratory findings with medical problems; and a real-time,
context-sensitive visualization of the medical record. Taken together,
these concepts form a comprehensive system for facilitating evidence-
based medicine in a real-world setting.
NEW BIOMATERIALS FOR TISSUE ENGINEERING
Tissue engineering holds the promise to repair and/or replace
damaged organs using biologic materials. For success in this area, a
number of scientific and bioengineering challenges must first be met.
For example, we must learn to produce, manipulate, and deliver
collections of cells not only as building blocks for tissues and organ
systems, but as models for studying drug development. Toward this goal,
NIBIB researchers have successfully transformed adult rat engineered
tissue cells into cells that form cartilage and bone. The two cell
types were integrated into separate layers, encapsulated in a gel-like
biocompatible material, and shaped into the ball structure of a human
jaw joint. Although more work is needed before this tissue-engineered
joint can be used in humans, it holds great potential for treating
patients with temporomandibular disorders, osteoarthritis, and
rheumatoid arthritis. These procedures could also be further refined
and adapted for developing artificial knee and hip joints.
Coronary stents are small devices that serve as a scaffold to prop
open the inside of an artery and provide vessel support. They are
commonly made of stainless steel or nylon mesh and therefore remain as
a permanent implant in a blood vessel. Although stents have
revolutionized the treatment of coronary artery disease, limitations
include an inflammatory reaction and the development of stent closure
due to blood clots forming within the device, a process termed
restenosis. To address this problem, NIBIB researchers have recently
developed a mechanically strong, hemocompatible, and X-ray visible
polymer as a noninflammatory fully-degradable coronary stent. While
designed as a stent, work continues to refine the device to serve
additionally as a drug-delivery vehicle. This may also have application
as a drug-delivery mechanism for other diseases, such as cancer.
SENSORS FOR MEDICINE
Biosensors are nanoscale or microscale devices that detect,
monitor, and transmit information about a physiological change, or
indicate the presence of various chemicals, gases, or biological
materials. Laboratory diagnostics used in hematology, clinical
chemistry, pathology, and microbiology already employ sensor
technologies to perform simultaneous measurements for many substances
in urine, blood, saliva, sweat, and interstitial fluids. The Institute
has an active research program in sensor technologies and continues to
expand this important area. For example, NIBIB researchers are
engineering recombinant antibody fragments (recAbs) that will increase
the sensitivity and specificity of a type of biosensor called a
piezoimmunosensor. Piezoimmunosensors have been proposed for almost 20
years; however, there has been no procedure for providing a sensing
layer that is uniform, chemically stable during the measurement
process, and contains high numbers of binding sites. By creating
tightly packed monolayers of recAbs that will bind to the surface of
the sensing unit, researchers are solving this problem while also
preventing non-specific interactions with molecules, and thus improving
specificity.
Other researchers are focusing on the design and fabrication of
miniaturized implantable responsive drug delivery devices that
integrate a smart drug delivery system with a biosensor. These drug
delivery systems are aimed at providing individualized therapies that
monitor the patient's body chemistry and control drug flow as needed.
NIH ROADMAP
To transform the Nation's medical research capabilities and to
speed the movement of research discoveries from the bench to the
bedside and into medical practice, the NIH has laid out a series of
far-reaching initiatives known collectively as the NIH Roadmap for
Medical Research. The NIH Roadmap focuses on the most compelling
opportunities in three main areas: new pathways to discovery, research
teams of the future, and re-engineering the clinical research
enterprise.
The NIBIB mission also strongly supports the NIH Roadmap
initiative, since the Roadmap goal is to facilitate the development of
innovative, novel and multidisciplinary science and technology that has
the potential to further advances in health care. For example, the
NIBIB is participating in an initiative that will facilitate the
formation of collaborative research teams capable of generating novel
probes for molecular and cellular imaging. The overall goal is to
establish programs to create complete tool sets for the detection of
single molecule events in living cells and to generate new strategies
for dramatically increasing the imaging resolution of dynamic cellular
processes.
Other areas of immediate interest to and supported by the NIBIB
include the development of nanomedicine technologies, new tools for the
study of proteomics and metabolic pathways, data and techniques for
computational biology, and advances in bioinformatics. The NIBIB also
strongly supports the NIH Roadmap theme on research teams of the future
through sponsoring multidisciplinary research and interdisciplinary
training.
MULTIDISCIPLINARY RESEARCH TEAMS
The value of collaboration among disciplines and organizations has
long been recognized as important for developing novel approaches to
problems in biology and medicine, and for effectively translating
research results to patient applications. We are pleased to report that
there have already been some successful ``NIBIB partnerships'' between
biomedical engineers and imaging scientists that have had significant
impacts on healthcare. For example, an ongoing Bioengineering Research
Partnership team is using fMRI to integrate information on the
suspected location of brain seizures with information about surrounding
brain function in order to improve surgical outcome and reduce or
eliminate seizures. In one early phase study, surgery employing fMRI
strategies was used to almost eliminate seizures in a patient who had
been suffering from as many as 100 seizures daily.
In conclusion, the NIBIB is dedicated to promoting the development
of emerging technologies and interdisciplinary collaborations that
drive healthcare advances. I would be pleased to respond to any
questions that the Committee may have.
______
Prepared Statement of Dr. Jack Whitescarver
Mr. Chairman and Members of the Committee, I am pleased to present
the President's budget request for the AIDS research programs of the
NIH for fiscal year 2005, a sum of $2,930,397,000 an increase of 5,000
above the comparable fiscal year 2004 appropriation.
The NIH represents the largest and most significant public
investment in AIDS research in the world a comprehensive program of
basic, clinical, and behavioral research on HIV infection and its
associated opportunistic infections and malignancies. Perhaps no other
disease so thoroughly transcends every area of clinical medicine and
scientific investigation, crossing the boundaries of the NIH
institutes. The Office of AIDS Research (OAR) plays a unique role at
the NIH. OAR coordinates the scientific, budgetary, and policy elements
of the NIH AIDS program, supported by nearly every Institute and
Center; prepares an annual comprehensive trans-NIH plan and budget for
all NIH-sponsored AIDS research; facilitates NIH involvement in
international AIDS research activities; and identifies and facilitates
scientific programs for multi-institute participation in priority areas
of research.
WORLDWIDE PANDEMIC
AIDS is the deadliest epidemic of our time. More than 22 million
people have already died of AIDS--3 million of them in 2003 alone--the
largest number ever. HIV has already infected more than 60 million
people around the world, and AIDS has surpassed tuberculosis and
malaria as the leading infectious cause of death worldwide.\1\
---------------------------------------------------------------------------
\1\ ``Report on the Global HIV/AIDS Epidemic: July 2002,'' (UNAIDS/
WHO, Geneva, Switzerland, 2002).
---------------------------------------------------------------------------
The United Nations General Assembly's Declaration of Commitment on
HIV/AIDS states ``. . . the global HIV/AIDS epidemic, through its
devastating scale and impact, constitutes a global emergency and one of
the most formidable challenges to human life and dignity, as well as to
the effective enjoyment of human rights, which undermines social and
economic development throughout the world and affects all levels of
society national, community, family, and individual.'' \2\ According to
a U.N. report, ``The epidemic has not only killed people; it has
imposed a heavy burden on families, communities and economies. The
misery and devastation already caused by HIV/AIDS is enormous, but it
is likely that the future impact will be even greater . . . The HIV/
AIDS epidemic has erased decades of progress in combating mortality and
has seriously compromised the living conditions of current and future
generations. The disease has such a staggering impact because it
weakens and kills many people in their young adulthood, the most
productive years for income generation and family caregiving. It
destroys families, eliminating a whole generation crucial for the
survival of the younger and older persons in society.'' The report also
highlights ``the long-term damage accruing to human capital, as
children's education, nutrition and health suffer directly and
indirectly as a consequence of HIV/AIDS. The effects of lowered
investment in the human capital of the younger generation will affect
economic performance for decades to come, well beyond the timeframe of
most economic analysis.'' \3\ Another dimension to the epidemic in
Africa was cited in the New York Times: ``As a result of HIV, the
worst-hit African countries have undergone a social breakdown that is
now reaching a new level: African societies' capacity to resist famine
is fast eroding. Hunger and disease have begun reinforcing each
other.'' \4\
---------------------------------------------------------------------------
\2\ ``The Impact of AIDS'' (Department of Economic and Social
Affairs, United Nations, 2003).
\3\ Ibid.
\4\ A. de Waal, ``What AIDS Means in a Famine,'' New York Times,
11/19/02.
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A recent CIA report estimated that by 2010, five countries of
strategic importance to the United States--Nigeria, Ethiopia, Russia,
India, and China--collectively will have the largest number of HIV/AIDS
cases on earth.\5\ Foreign Affairs magazine stated: ``The spread of
HIV/AIDS through Eurasia, in short, will assuredly qualify as a
humanitarian tragedy--but it will be much more than that. The pandemic
there stands to affect, and alter, the economic potential--and by
extension, the military power--of the region's major states . . . Over
the decades ahead, in other words, HIV/AIDS is set to be a factor in
the very balance of power within Eurasia--and thus in the relationship
between Eurasian states and the rest of the world.'' \6\ Dramatic
increases in HIV infection also are occurring in Eastern Europe,
Central Asia, Latin America, and the Caribbean.
---------------------------------------------------------------------------
\5\ ``Intelligence Community Assessment: The Next Wave of HIV/AIDS:
Nigeria, Ethiopia, Russia, India, and China.'' (CIA, 2002).
\6\ ``The Future of AIDS,'' Foreign Affairs, November/December
2002.
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THE U.S. EPIDEMIC
According to CDC, the decline in death rates observed in the late
1990s, due largely to expanded use of new antiretroviral therapies
(ART) that prevent progression of HIV infection to AIDS, has now
leveled off; and AIDS incidence increased 2 percent in 2002 (over
2001). This means that the overall epidemic is continuing to expand.\7\
\8\ \9\ In addition, use of ART has now been associated with a series
of side effects and long-term complications that may have a negative
impact on mortality rates. HIV infection rates are continuing to climb
among women, racial and ethnic minorities, young homosexual men,
individuals with addictive disorders, and people over 50 years of
age.\10\ The appearance of multi-drug resistant strains of HIV presents
an additional serious public health concern.\11\ \12\ \13\ \14\ \15\
According to CDC reports, approximately one quarter of the HIV-infected
population in the United States also is infected with hepatitis C virus
(HCV). HIV/HCV co-infection is found in 50 to 90 percent of injecting
drug users (IDUs). HCV progresses more rapidly to liver damage in HIV-
infected persons and may also impact the course and management of HIV
infection, as HIV may change the natural history and treatment of
HCV.\16\ This expanding and evolving U.S. epidemic presents new and
complex scientific challenges.
---------------------------------------------------------------------------
\7\ CDC Year-End HIV/AIDS Surveillance Report for 2002 (CDC, 2003).
\8\ ``Centers for Disease Control and Prevention HIV Prevention
Strategic Plan Through 2005,'' (CDC, 2001).
\9\ ``HIV/AIDS Update--A Glance at the HIV Epidemic,'' (CDC, 2001).
\10\ ``U.S. HIV and AIDS Cases Reported Through June 2000,'' CDC
HIV/AIDS Surveillance Report, Vol. 12 (2002).
\11\ N. Loder, Nature 407, 120 (2000).
\12\ H. Salomon et al., AIDS 14, 17 (2000).
\13\ Y.K. Chow et al., Nature 361, 650 (1993).
\14\ M. Waldholz, ``Drug Resistant HIV Becomes More Widespread,''
Wall Street Journal, 2/5/99.
\15\ ``World Health Report on Infectious Diseases: Overcoming
Antimicrobial Resistance,'' (WHO, Geneva, 2000).
\16\ ``Frequently Asked Questions and Answers About Coinfection
with HIV and Hepatitis C Virus'' (CDC, 2002).
---------------------------------------------------------------------------
COMPREHENSIVE AIDS RESEARCH PLAN AND BUDGET
To address these compelling scientific questions, the OAR develops
an annual comprehensive trans-NIH AIDS research plan and budget, based
on the scientific priorities and opportunities that will lead to better
therapies and prevention strategies for HIV infection and AIDS. The
planning process is inclusive and collaborative, involving the NIH
Institutes, as well as eminent non-government experts from academia,
industry, foundations, and AIDS community representatives. The Plan
serves as the framework for developing the annual AIDS research budget
for each Institute and Center, for determining the use of AIDS-
designated dollars, and for tracking and monitoring those expenditures.
The planning process also serves to monitor and assess scientific
progress on an annual basis.
The Plan establishes the NIH AIDS scientific agenda in the areas
of: Natural History and Epidemiology; Etiology and Pathogenesis;
Therapeutics; Vaccines; and Behavioral and Social Science. In addition,
the plan addresses the cross-cutting areas of: Microbicides; Racial and
Ethnic Minorities; Women and Girls; Prevention Science; International
Research; Training, Infrastructure, and Capacity Building; and
Information Dissemination. In consultation with the Director of NIH,
the OAR determines the total annual AIDS research budget. Within that
total, the OAR establishes the AIDS research budgets for each NIH
Institute and Center, in accordance with the priorities and objectives
of the Plan, at each step of the budget development process up to the
Conference Committee. To accomplish this, OAR consults regularly with
the Institute and Center Directors. This process allows the OAR to
ensure that NIH AIDS research funds will be provided to the most
compelling scientific opportunities, rather than a distribution based
solely on a formula.
OAR plays a crucial role in identifying scientific areas that
require focused attention and facilitating multi-Institute activities
to address those needs. OAR fosters this research through a number of
mechanisms, such as designating funds and supplements to jump-start or
pilot program areas, sponsoring workshops or conferences to highlight a
particular research topic, and sponsoring reviews or evaluations of
research program areas to identify research needs.
The overarching priorities that continue to frame the NIH AIDS
research agenda are: prevention research to reduce HIV transmission,
including development of vaccines, microbicides, and behavioral
interventions; therapeutics research to develop simpler, less toxic,
and cheaper drugs and drug regimens to treat HIV infection and its
associated illnesses, malignancies, and other complications;
international research, particularly to address the critical needs in
developing countries; and research targeting the disproportionate
impact of AIDS on minority populations in the United States. All of
these efforts require a strong foundation of basic science, the bedrock
of our research endeavor.
VACCINES AND PREVENTION RESEARCH
Vaccine research remains a critical priority. As a result of
increased NIH funding, many new approaches to HIV vaccines are being
pursued. Although production of candidate vaccines for clinical study
has proceeded slowly, approximately 14 new candidate vaccines will
enter Phase I trials in the next 2 years. Several new combinations of
products, which are expected to provide better immune responses, also
will be tested in Phase I or II trials. The Dale and Betty Bumpers
Vaccine Research Center, located on the NIH campus, recently launched
the first Phase I clinical trial of a multi-clade, multi-gene vaccine
candidate. The development of vaccine candidates also requires
sufficient quantities of non-human primates for preclinical testing.
In addition to vaccines, our biomedical prevention research
priorities include the development topical microbicides; strategies to
prevent mother-to-child transmission, including a better understanding
of risk associated with breast-feeding; and management of sexually
transmitted diseases (STDs). NIH also supports behavioral research
strategies, including interventions related to drug and alcohol use.
Efforts continue to identify the most appropriate intervention
strategies for different populations and sub-epidemics in the United
States and around the world.
NEW CHALLENGES IN THERAPEUTICS RESEARCH
While multiple ART drug combinations continue to successfully
reduce viral load and restore immune responses in many HIV-infected
individuals, these regimens also can result in serious toxicities and
side effects, single- and multiple drug-resistance, and other
complications that make them unacceptable for some individuals. These
side effects and complications appear to be increasing as HIV-infected
individuals continue on drug regimens. More deaths occurring from liver
failure, kidney disease, and cardiovascular complications are being
observed in this patient population. NIH-sponsored research efforts
continue to develop better antiretroviral drugs and treatment regimens
that demonstrate less toxicity, activity in viral and cellular
reservoirs, reduced development of drug resistant virus, improved
pharmacodynamics and pharmacokinetics, easier compliance, and lower
cost.
While the incidence of certain opportunistic infections (OIs) and
malignancies has decreased with the advent of ART, the number of cases
of TB, multiple drug resistant TB, and other coinfections such as
Hepatitis B virus and Hepatitis C virus has increased. The development
of practical and affordable treatment regimens against HIV coinfections
and endemic diseases in developed and developing nations is an NIH
priority.
INTERNATIONAL RESEARCH
NIH bears a unique responsibility to address the urgency of the
global AIDS epidemic. To meet that need, the OAR established an
initiative and strategic plan for global research on HIV/AIDS and has
significantly increased research efforts in the past several years to
benefit resource- and infrastructure-poor nations. NIH supports a
growing portfolio of research conducted in collaboration with
investigators in developing countries. Results of this research benefit
the people in the country where the research is conducted, as well as
people affected by HIV/AIDS worldwide. Critical to the success of these
international studies are foreign scientists who are full and equal
partners in the design and conduct of collaborative studies. To that
end, NIH also supports international training programs and initiatives
that help build infrastructure and laboratory capacity in developing
countries where the research is conducted.
WOMEN AND MINORITIES
Women experience HIV/AIDS differently from men. NIH research has
demonstrated that women progress to AIDS at lower viral load levels and
higher CD4 counts than men. Women also experience different clinical
manifestations and complications of HIV disease. These findings may
have implications for care and treatment of HIV-infected women,
particularly with ART. There are many research questions that remain
unanswered about specific characteristics of women and girls that might
play a role in transmission, acquisition, or resistance to HIV
infection during different stages of the life course.
In many U.S. urban centers, HIV seroprevalence rates mimic those
found in some developing nations. These findings, along with the
resurgence of STDs and associated high-risk behaviors, demonstrate the
need for comprehensive strategies to decrease HIV transmission in
affected vulnerable populations, and improve treatment options and
treatment outcomes. OAR is directing increased resources toward
research to develop new interventions that will have significant impact
on these groups. These include interventions that address the co-
occurrence of other STDs, hepatitis, drug abuse, and mental illness;
and interventions that consider the role of culture, family, and other
social factors in the transmission and prevention of these disorders in
minority communities. NIH is making significant investments to improve
research infrastructure and training opportunities for minorities and
will continue to ensure the participation of minorities in AIDS
clinical trials, as well as in natural history, epidemiologic, and
prevention studies.
SUMMARY
The human and economic toll of the AIDS pandemic is profound,
demanding a unique response that is complex, comprehensive, multi-
disciplinary, and global. The NIH role in this response is fundamental
and unprecedented. The nation's investment in AIDS research is reaping
even greater dividends, as AIDS-related research is unraveling the
mysteries surrounding many other infectious, malignant, neurologic,
autoimmune, and metabolic diseases. The authorities of the OAR allow
NIH to pursue a united research front against the global AIDS epidemic.
We are deeply grateful for the continued support the Administration and
this Committee have provided to our efforts.
______
Prepared Statement of Dr. Francis S. Collins
Mr. Chairman, I am pleased to present the President's budget
request for the National Human Genome Research Institute for fiscal
year 2005, a sum of $492,670,000, which reflects an increase of
$13,842,000 over the fiscal year 2004 Final Conference appropriation.
Following the completion of the Human Genome Project last year, the
National Human Genome Research Institute (NHGRI) of the National
Institutes of Health announced an ambitious plan for applying genomics
to human health benefits. A Vision for the Future of Genomics Research,
the outcome of almost two years of intense discussions with over 600
scientists and members of the public, has three major areas of focus:
Genomics to Biology, Genomics to Health, and Genomics to Society.
Several ambitious projects are already underway to help achieve this
vision including the International Haplotype (HapMap) Project, the
Encyclopedia of DNA Elements (ENCODE), the NIH Roadmap initiative on
Molecular Libraries, and a new Ethical, Legal and Social Implications
(ELSI) Center initiative. As we enter the genomic era, the continued
support of biomedical research in this area is more vital than ever.
ONGOING NHGRI INITIATIVES
International HapMap Project
To study genetic variation more effectively across the human
genome, the NHGRI and a team of partners has launched the International
HapMap Project. The goal of the project is to determine the common
patterns of DNA sequence variation in the human genome, and to make
this information freely available in the public domain. This
international consortium is developing a map of these patterns across
the genome by determining the genotypes of one million or more sequence
variants in DNA samples from populations with ancestry from Africa,
Asia, and Europe. When complete, the HapMap will enable the discovery
of sequence variants that affect common disease, the development of
diagnostic tools, and the ability to choose targets for therapeutic
intervention. Detailed information about the HapMap project was
published in a landmark article in Nature, and updated details can be
found on the web at www.hapmap.org.
Comparative Genomics to Understand the Human Genome
One of the most powerful approaches for unlocking the secrets of
the human genome is comparative genomics. While the completed sequence
of the human genome represents a milestone of historic proportions, a
daunting challenge that still lies ahead is to interpret its biological
meaning and function. Recently sequenced genomes of the mouse, rat, and
a wide variety of other organisms--from yeast to chimpanzees--prove
that the genomes of other species are amongst the most powerful tools
in advancing understanding of the human genome. The current NHGRI-
supported, large-scale sequencing centers have built a prodigious
capacity for, and expertise in, sequencing entire genomes. The combined
capacity of these centers is expected to yield the equivalent of about
20 additional draft vertebrate genomes in just the next three years.
These additional species sequences will provide exciting new insights
into the function of the human genome, and will assist genome
scientists in translating the basic findings of the Human Genome
Project into tangible applications, including the diagnosis,
prevention, and treatment of disease.
ENCODE--ENCyclopedia Of DNA Elements
To understand the meaning of the human instruction book, the
genome, the identities and precise locations of all functional elements
must be determined. Thus, the NHGRI has launched the ENCyclopedia Of
DNA Elements (ENCODE) project to identify these elements
comprehensively. The ENCODE project seeks to characterize the tools
needed for exploring genomic sequence, improve those tools when
necessary, and define a clear path for the determination of all of the
functional elements in the entire human genome. On October 9, 2003, the
NHGRI announced the first ENCODE grants in a three-year, $36 million
project (www.genome.gov). ENCODE begins as a pilot effort to evaluate
methods for the exhaustive identification and verification of
functional sequence elements in a carefully selected 30 million base
pairs, or about one percent, of human genomic DNA. This will require
access to information, resources, ideas, expertise, and technology
beyond the capabilities of any single group. Therefore, a consortium of
investigators with diverse backgrounds and expertise will work
cooperatively to carry out this project to: (1) evaluate rigorously the
relative merits of a varied set of computational and experimental
techniques, technologies, and strategies for identifying the functional
elements in human genomic sequence, and (2) test the capabilities of
such methods to scale up efficiently to allow, ultimately, analysis of
all the functional elements encoded in the entire human genome
sequence.
Centers Of Excellence In Genomic Science (CEGS)
The NHGRI Centers Of Excellence In Genomic Science (CEGS) program
has been in place for four years. This program is a centerpiece of the
Institute's effort to stimulate new interdisciplinary approaches to
genomic research and technology development. A total of about 10 CEGS
grants are ultimately expected to be funded. These will generally be
five-year awards of up to $3 million per year. Seven awards have been
made to date; each involves multiple investigators and disciplines, and
several cut across departments and institutions. A grantee meeting in
October 2003 stimulated new collaborations and identified ways to share
CEGS grant data and resources with the larger research community.
Clinical Research Activities in the NHGRI Intramural Program
Research efforts of NHGRI Division of Intramural Research (DIR)
investigators are aimed at deciphering the genetic contributions to
common disorders, to provide a better understanding of diseases such as
cancer, diabetes, and heart disease, as well as to a number of less
common but equally debilitating afflictions. DIR investigators have
been at the forefront of scientific innovation, developing a variety of
research approaches that accelerate the understanding of the molecular
basis of disease. These include the development of DNA microarray
technologies for large-scale molecular analyses, innovative computer
software to study fundamental biological problems, animal models
critical to the study of human inherited disorders, and the clinical
testing of new therapeutic approaches for genetic disease. Three
examples of gene discoveries within the past year include the gene
responsible for Hutchinson-Gilford progeria syndrome, the disease
causative gene for Charcot-Marie-Tooth disease type 2D, and a gene
variant that contributes to the risk of type 2 diabetes. These and
other advances should ultimately lead to improved diagnostic,
prevention, and treatment strategies having a direct impact on human
health.
NEW INITIATIVES
The NHGRI is very enthusiastic about the initiatives included in
the NIH Roadmap and is deeply involved in implementation plans for
several of the projects embodied in the ``New Pathways to Discovery''
theme.
Molecular Libraries
As part of its Vision for the Future of Genomics Research, and in
partnership with many other NIH Institutes as part of NIH's new Roadmap
for Medical Research, the NHGRI is taking a lead role in providing
access to high throughput screens for small organic molecules to public
sector researchers. These small molecules can be used as chemical
probes to study cellular pathways in great depth and will broadly
enable public and private biomedical research into basic biology and
accelerate the validation of new therapeutic targets, and thus the
discovery of new drugs. For this effort to provide maximal benefits,
the library of small molecules must contain a sufficient number of
compounds. To build such a library, a network of six national centers
will establish a common collection of 500,000 or more chemically
diverse small molecules, of both known and unknown activities.
Investigators who develop assays suitable for high throughput screening
will apply for access to these centers. After peer review, suitable
assays will be run through a screen of 500,000 or more compounds, and
the positives subjected to a first pass of chemical optimization to
generate useful compounds. We anticipate that this new resource will
catalyze a genuine paradigm shift, because it will give academic
investigators a new and powerful research tool not previously at their
disposal.
$1,000 Genome Sequence
Current sequencing costs are too high to collect the quantity and
quality of soome sequences optimal for research and clinical
applications. Completely sequencing the genomes of many individuals
would greatly advance understanding of the role of DNA sequence
variation in human health, but using DNA sequence information for care
of individuals is not possible at current costs. Thus, NHGRI has
launched an aggressive program to develop technologies to lower the
cost of DNA sequencing dramatically. The goal for the first five years
of this program is to develop the capability to produce a high quality
draft sequence for a large, complex (e.g., mammalian) genome for
$100,000. The goal of the second phase, which is estimated to take ten
years, is producing a genome sequence for $1,000. Once achieved, a
$1,000 genome analysis would be of great use to correlate DNA
information with health outcomes. This includes determining genes in
each individual that predispose that individual to specific diseases,
and assessing which drugs are likely to elicit adverse reactions in
each individual, so that drugs can be used more effectively and with
fewer side effects.
Centers for Excellence in ELSI Research
The NHGRI Ethical Legal and Social Implications (ELSI) research
program recently released a Request for Applications inviting proposals
for the development of Centers of Excellence in ELSI Research (CEER).
The CEER program is designed to support the development of groups that
will pursue research questions best approached through intensive and
extended collaboration among investigators from multiple disciplines,
using diverse methodologies. CEER investigators are encouraged to
consider new ways to explore these questions, design innovative and
efficient research projects, propose and disseminate health or social
policy options based on Center research, and, when feasible, facilitate
policy development pertinent to a specific issue. Center applicants are
particularly encouraged to identify cutting edge research topics and
approaches that may lead to high payoff solutions to important ELSI
problems.
Intramural Social and Behavioral Research Branch
The NHGRI has formed a new Social and Behavioral Genetics Research
Branch within its intramural research program. The main focus of the
Branch is to conduct research on the social and behavioral aspects of
translating genomic discoveries into improved health. The Branch will
also: (1) study innovative ways of applying genetic discoveries to
promote health and well-being; (2) apply social, behavioral, and
communication theories to understand how to communicate genetic risk
effectively; (3) develop and refine evidence-based methods of
communicating genetic risk to individuals, families, communities, and
populations; (4) seek to understand how social factors influence
genetic discoveries and research; and (5) investigate the ethical and
public policy implications of genetic research and the use of genetics
in clinical practice.
OTHER AREAS OF INTEREST FOR NHGRI
Genetic Discrimination
The NHGRI remains concerned about the risk of genetic
discrimination and supports the President's call for federal
legislation. Many Americans are worried that insurers and employers may
use genetic information to deny, limit, or cancel their health
insurance or to discriminate against them in the workplace. A total of
41 States have enacted legislation on discrimination in health
insurance and 31 have enacted legislation on workplace genetic
discrimination. However, only comprehensive federal legislation can
guarantee everyone in the United States protection from genetic
discrimination. Last October, the full U.S. Senate voted unanimously
(95-0) in favor of the ``Genetic Information Nondiscrimination Act of
2003'' (S. 1053), which would address this problem. It is hoped that
the House will soon take similar steps.
Intellectual Property Rights in Genetics and Genomics Research
NHGRI has long worked on issues of intellectual property related to
genetic and genomic data. The NHGRI ELSI program plans soon to issue a
new initiative to encourage studies of the role of intellectual
property rights in genetics and genomics research, as well as the
impact of exclusivity on progress in these fields. The initiative will
support legal, economic, political science, and statistical analyses
and empirical investigations of theories and practices of rights
holders, stakeholders, and researchers in genetics and genomics
research and development, with the specific goal of helping build the
research base necessary to inform the rational development of future
policy options regarding intellectual property in genetics, and
genomics.
The NHGRI, with several other NIH Institutes, has recently provided
funds for a National Academy of Sciences' study, ``Intellectual
Property in Genomic and Protein Research and Innovation.'' This 18-
month study, involving experts from law, public policy and genomics,
will address such important questions as: What is the impact of
intellectual property and licensing on genetic and proteomic research?
What policy options should be considered in this area? How have other
regions of the world addressed these issues? It is hoped that this
study will provide insights on how to address the thorny issues
surrounding the interface of intellectual property, biomedical
research, and patient care.
Direct-to-Consumer Marketing of Genetic Tests
Marketing of products or services that promise to provide consumers
with genetic insights into personal health has proliferated
dramatically in recent years. NHGRI's intramural Division of Bioethics
has systematically studied this issue. So far, researchers have found
that many direct-to-consumer (DTC) advertisements exaggerate the
scientific basis of claims made and/or fail to communicate effectively
the current limitations of the specific genetic knowledge discussed. In
particular, the Internet has provided a powerful medium for the
construction of ``informational'' resources through which DNA analysis
is often linked to a claim to individualize consumer profiles for
specific products available through the website. Additionally, the
first example of a multi-media DTC advertising campaign for a genetic
test, the BRCA1/2 test, was piloted in two metropolitan areas in the
last year. The NHGRI recently held a workshop to assess DTC marketing
of genetic tests, and considered the scope of the practice and possible
policy options. The NHGRI will work with the Secretary's Advisory
Committee on Genetics Health and Society on this issue.
Trans-NIH Obesity Initiative
The NHGRI Deputy Director represents the Institute on the trans-NIH
obesity working group. We believe that this initiative is vitally
important, and that the genomic tools produced by the Human Genome
Project can be of considerable utility in discerning the role of genes
and environment in causing obesity, and in predicting which obese
individuals will develop which diseases.
CONCLUSION
With the completion of the human genome sequence, we have fully
entered the genomic era. The NHGRI has now spearheaded many specific
and innovative initiatives to understand how genetics affects human
health, the ultimate motivation for the Human Genome Project. The most
interesting and important applications of genomics lie not behind us,
but ahead of us. Continued investment by the Congress in genetic/
genomic research is vital to our efforts to enhance the health of all.
______
Prepared Statement of Dr. Richard J. Hodes
Mr. Chairman and Members of the Committee: The NIA is requesting an
fiscal year 2005 budget of $1,055,666,000, an increase of $31,068,000
or 3 percent over the comparable fiscal year 2004 appropriation.
Thank you for this opportunity to participate in today's hearing. I
am Dr. Richard Hodes, Director of the NIA, and I am pleased to be here
today to tell you about our progress making and communicating
scientific discoveries that will improve the health and well-being of
older Americans.
There are today approximately 35 million Americans ages 65 and
over, according to the U.S. Bureau of the Census. Thanks to
improvements in health care, nutrition, and the overall standard of
living, these men and women are more likely than ever before to be
healthy, vigorous, and productive: Studies confirm that disability
among America's elders has declined steadily over the past decade. More
older Americans are able to participate in ``instrumental activities of
daily living,'' such as performing household chores and managing their
own medications, while fewer are experiencing limitations in basic
physical tasks such as walking or climbing stairs.
At the same time, diseases of aging continue to affect many older
men and women, seriously compromising the quality of their lives. For
example, more than half of all Americans over age 65 show evidence of
osteoarthritis in at least one joint. Over half of Americans over age
50 have osteoporosis or low bone mass. Cardiovascular disease, cancer,
and diabetes remain common among older Americans. And as many as 4.5
million Americans suffer from Alzheimer's disease (AD), the most common
cause of dementia among older persons.
The mission of the National Institute on Aging is to improve the
health and well-being of older Americans through research. In support
of this mission, the Institute conducts and supports an extensive
program of research on all aspects of aging, from the basic cellular
and molecular changes that occur as we age, to the prevention and
treatment of common age-related conditions, to the behavioral and
social aspects of growing older, including the demographic and economic
implications of an aging society. In addition, the NIA is the lead
federal agency on Alzheimer's disease research; our activities in that
area encompass prevention, detection, clinical trials, and caregiver
issues. Finally, our education and outreach programs provide vital
information to older people across the United States on a wide variety
of topics, including living with chronic conditions such as arthritis
or diabetes, caring for a loved one with Alzheimer's disease, and
maintaining optimal health through exercise.
The NIA works to rapidly translate research findings into practical
interventions and information that will benefit older Americans. This
may involve enhancing our methods of communicating important research
findings to physicians or the public; creating opportunities for
patients to benefit from groundbreaking research through participation
in clinical trials; or even recognizing the potential of a very basic
finding in a mouse, a worm, or a molecule to eventually have a powerful
impact on the public health.
For example, recent findings in C. elegans, a tiny worm that is
frequently used for genetic studies, are providing important insights
about fat regulation and storage that may lead to improved
understanding of overweight and obesity in humans. NIH-supported
researchers used RNA interference (RNAi), a technique in which genes
are inactivated one at a time to determine their function, to screen
the worm's genome and found some 417 genes involved with fat regulation
and storage. Many of the genes they found have human counterparts, a
number of which had not been previously implicated in the regulation of
fat storage. Overweight and obesity are widespread in the United States
and are associated with an array of health problems, including heart
disease, stroke, osteoarthritis, adult-onset diabetes, and certain
types of cancer; the genes identified in C. elegans may ultimately
suggest new targets for treating human obesity and its associated
diseases.
Another recent basic discovery, this one in mice, may have profound
implications on the field of reproductive biology. Since the 1950s,
scientists have believed that women are born with all the oocytes
(eggs) they will ever have, and that these eggs die off as a woman
ages, with fertility diminishing and, at menopause, disappearing as a
result. However, NIH-supported researchers recently found that oocyte-
containing follicles continue to develop in the ovaries of adult mice.
If this finding is confirmed--and extended to humans--it could lead not
only to new treatments for premature ovarian failure (which affects
some 250,000 American women under age 40, according to the National
Institute of Child Health and Human Development), but also to
interventions to delay menopause and extend fertility.
NIA-supported investigators in all fifty states are conducting
research that is changing the way we prevent, diagnose, and treat the
diseases of aging. NIA also supports networks of centers that focus on
specific topics, including demography and the basic biology of aging.
There are currently 29 NIA-supported Alzheimer's Disease Centers
(ADCs), at which investigators are working to translate research
advances into improved care and diagnosis for AD patients while
focusing on the program's long-term goal--finding ways to treat and
possibly prevent AD. Many ADCs have satellite facilities that offer
diagnostic and treatment services and collect research data in
underserved, rural, and minority communities. Another type of Center,
the Edward R. Roybal Centers for Research on Applied Gerontology,
translates behavioral and social research findings into practical
outcomes for older adults. Each of the six Roybal Centers addresses one
or more central themes (e.g., cognitive influences on physician/patient
interaction affecting medical compliance; safe driving behavior; social
role adjustment upon retirement).
The NIA also supports a variety of clinical trials, frequently in
collaboration with one or more NIH Institutes or other organizations.
For example, NIA is currently supporting 25 AD clinical trials, seven
of which are large-scale prevention studies. These trials are testing
agents such as anti-inflammatory drugs and anti-oxidants for their
effects on slowing progress of the disease, delaying AD's onset, or
preventing the disease altogether. Other intervention trials are
assessing the effects of various compounds on the behavioral symptoms
(agitation, aggression, and sleep disorders) of people with AD. In
addition to AD, NIA supports clinical trials for a number of other
conditions, including cardiovascular disease, Parkinson's disease, and
certain types of cancer.
A major clinical trial in which NIA-supported researchers took part
is the Diabetes Prevention Program, a multi-institutional study that
was initiated by the National Institute on Diabetes and Digestive and
Kidney Diseases and was designed to identify interventions that could
prevent or delay the development of type 2 diabetes. The researchers
found that people who are at high risk for diabetes can sharply reduce
their risk by adopting a low-fat diet and moderate exercise regimen.
This effect was most pronounced among study participants age 60 and
over. Treatment with the drug metformin (Glucophage) also reduced
diabetes risk among study participants, but for unknown reasons was
less effective among older participants. With other participating NIH
Institutes, we are continuing to follow the study participants to
determine long-term effectiveness of these interventions.
The NIA also has a number of ongoing or planned special initiatives
on diverse research topics. These include:
Health Disparities.--The NIA's Healthy Aging in Neighborhoods of
Diversity Across the Lifespan (HANDLS) project is a community-based
study of health disparities among different racial, ethnic, and
socioeconomic groups in Baltimore. The purpose of HANDLS is to
disentangle the effects of race and socioeconomic status on risk
factors for morbidity and mortality, incidence and progression of pre-
clinical disease, development and persistence of health disparities,
longitudinal health status, and health risks. The pilot phase of the
study was completed in December 2001, and the full-scope study is now
being planned for implementation in 2004-2005. Unique to the HANDLS
study is the use of two fully-equipped mobile research laboratories
that enable investigators to collect data directly in the neighborhoods
under study, establishing links with the community and increasing both
the interest of potential participants and the retention rate.
Neuroimaging.--The NIA is developing an Alzheimer's Disease
Neuroimaging Initiative, a longitudinal, prospective, natural history
study of normal aging, mild cognitive impairment, and early AD to
evaluate neuroimaging techniques such as magnetic resonance imaging
(MRI) and positron emission tomography (PET). The study objectives are
to:
--Identify the best markers for early diagnosis of AD
--Identify markers for following disease progression and monitoring
treatment response
--Develop surrogate endpoints for clinical trials
--Decrease time and expense of drug development
--Establish methods for the collection, processing, and distribution
of neuroimaging data in conjunction with other biological,
clinical, and neuropsychological data
The initiative is planned as a partnership among the NIA/NIH,
academic investigators, the pharmaceutical and imaging equipment
industries, the Food and Drug Administration, the Centers for Medicare
and Medicaid Services, and the NIH Foundation, with participation from
the Alzheimer's Association and the Institute for the Study of Aging.
The clinical, imaging, and biological data and samples will be made
available, with appropriate safeguards to ensure participant privacy,
to scientific investigators in the academic and industrial research
communities.
Testosterone replacement in men.--Levels of circulating
testosterone decline as men age, and this decline may be related to
decrements in physical and cognitive functioning--for example, recent
research suggests that older men with lower levels of free, or unbound,
testosterone circulating in their bloodstreams could be at increased
risk of developing Alzheimer's disease (AD). Increasingly, middle-aged
and older men are turning to testosterone replacement therapy (TRT) to
forestall these symptoms: In 2002, over 800,000 men received some form
of testosterone replacement. However, as with the use of hormone
replacement therapy among women prior to the release of the Women's
Health Initiative results demonstrating serious HRT-related risks, men
are using TRT in the absence of clear scientific data supporting its
use. A multi-disciplinary panel, led by the Institute of Medicine and
supported by the NIA and the National Cancer Institute, recently
evaluated the pros and cons of conducting clinical trials of
testosterone replacement therapy in older men to answer many of the
lingering questions about the effects of this hormone in the aging
body. The NIA is considering the IOM recommendations very carefully and
will act on the recommendations to begin clinical trials to determine
the efficacy of testosterone in treating symptomatic older men with low
testosterone levels.
Genetics.--The NIA has established a new AD Genetics Initiative, a
program to accelerate the pace of AD genetics research by creating a
large repository of DNA and cell lines from families with multiple AD
cases. The goal of this initiative is to develop strategies for
identifying the remaining late-onset AD (LOAD) risk factor genes,
associated environmental factors, and the interactions of genes and the
environment. The NIA's AD Genetics Initiative will intensify sample
collection and encourage data sharing by providing access to the
repository to qualified investigators. To date, several well-integrated
components of the Genetics Initiative have been launched. Mechanisms to
efficiently identify and share large numbers of samples for AD genetic
analysis have been developed through the recently-enlarged National
Cell Repository for AD (NCRAD), and eighteen of the NIA's Alzheimer's
Disease Centers have received supplemental funding to recruit new
family members participation. Uniform standards for sample collection
have also been developed. As of late January, over 200 families have
been evaluated and enrolled, and over 800 blood samples have been
logged at NCRAD. A clinical task force has been established which is
helping to determine the correct phenotypic data to be included with
the biological samples. A major goal is the long-term follow-up of
individuals participating in the study.
In order to publicize the initiative, the NIA Office of
Communications and Public Liaison, together with its Alzheimer's
Disease Education and Referral Center, Columbia University, and NCRAD,
partnered with the Alzheimer's Association to conduct focus groups and
develop publicity materials to help recruiting efforts. These publicity
materials, including a workbook, CD ROM, fact sheet, and brochure were
distributed at the a recent meeting of the ADCs and will now be sent to
ADCs and Alzheimer's Association chapters to help recruiting efforts.
Longevity.--The NIA has formed a Longevity Consortium to help
identify and understand genetic and other factors that predispose to
human longevity or protect against multiple age-related conditions, a
major goal in aging research. The Consortium is an innovative system
for expeditious generation, review, and funding of new projects as
opportunities arise, and includes epidemiologists, geneticists,
population biologists, statisticians, and others with an interest in
the genetic and molecular basis for longevity. Participants can draw on
the study populations of 15 of the largest human aging studies,
including the Cardiovascular Health Study, the Women's Health
Initiative, Health ABC, the Study of Osteoporotic Fractures, the
Rotterdam Study, the Honolulu Heart Study, and the New England
Centenarian Study. Altogether, Consortium researchers will have access
to data on some 200,000 study subjects.
Demography.--As the percentage of Americans over age 65 increases,
profound societal changes will likely occur. NIA-supported researchers
are exploring the changing demographic, social, and economic
characteristics of the older population. Research embraces topics such
as: trends in the age-structure of populations; changes in levels of
disease and disability; economic costs of disability; cost-
effectiveness of interventions; migration and geographic concentrations
of the elderly; decision-making about retirement; pensions and savings;
the relationship between health and economic status; and health
disparities by gender and race. The results of this research often have
important implications for public policy. Such research often involves
large datasets that are frequently co-sponsored by NIA and other
government agencies in the United States and overseas. These include:
--Health and Retirement Study, a biennial survey of more than 22,000
Americans over age 50, which provides data for researchers,
policy analysts, and program planners who are making major
policy decisions that affect retirement, health insurance,
saving and economic well-being.
--National Long-Term Care Study, which explores trends in the
prevalence of self-rated old age disability and physical,
cognitive, and sensory limitations.
--Longitudinal Study of Aging, a long-term study in which the NIA
participates with the National Center for Health Statistics.
--Panel Study of Income Dynamics, begun in 1968 and conducted by the
National Science Foundation, is a nationally representative
longitudinal study that collects information on U.S.
households. Notably, the PSID contains information on
approximately 5,000 heads of households and spouses who are
baby boomers (born 1945-1964)--a cohort not yet represented in
the Health and Retirement Study (HRS). Continued data from the
PSID will shed light on individual household saving behavior of
the baby boom generation and its neighboring age cohorts.
Health Communication.--Communication of research-based health
information is another key activity of the NIA, and the Institute uses
both traditional and innovative means to disseminate information. In
2003, the Pew Internet and American Life survey found that 22 percent
of Americans age 65 or older have access to the Internet, and that 58
percent of these ``wired seniors'' had used the Internet to look for
information about a specific disease. However, NIA-supported research
has demonstrated that with age come changes in cognition (such as
working memory, perceptual speed, text comprehension) and vision
(including loss of ability to detect fine details, less light reaching
the retina, and loss of contrast sensitivity) that could hinder the
older person's ability to use the Internet easily and effectively. To
respond to the unique needs of Internet users over 60, the NIH launched
NIHSeniorHealth.gov on October 23, 2003. Developed by the NIA and the
National Library of Medicine, and featuring content developed in
collaboration with several other NIH Institutes, this web site is easy
for older adults to read, understand, remember, and navigate. For
example, the site features large print and short, easy-to-read segments
of information repeated in a variety of formats--such as open-captioned
videos and short quizzes--to increase the likelihood it will be
remembered. Consistent page layout and prompts help users move from one
place to another on the site without feeling lost or overwhelmed. The
site also has a ``talking'' function, which allows users the option of
reading the text or listening to it as it is read to them.
The risk of many diseases increases with age, so the site focuses
on health topics or specific diseases that are of particular interest
to older people, including Alzheimer's disease, Alzheimer's disease
caregiving, arthritis, balance problems, breast cancer, colorectal
cancer, exercise for older adults, hearing loss, lung cancer, and
prostate cancer. Upcoming and planned topics include complementary and
alternative medicine, diabetes, falls, shingles, vision changes, and
others. Each topic provides general background information, quizzes,
frequently asked questions (FAQs), open-captioned video clips,
transcripts for the videos, and photos and illustrations with captions.
From its launch in October 2003 through late January,
NIHSeniorHealth.gov has received over a million page views and been
visited by nearly 118,000 unique visitors.
The NIA also maintains a large selection of lay-language Age Pages,
which cover an array of topics relevant to older people and include
information on a number of diseases and conditions, suggestions for
coping with these conditions, and information on other resources. Most
of the Age Pages have been translated into Spanish.
At a March 2002 hearing of this Committee entitled ``Bench to
Bedside,'' Chairman Regula recommended that NIA and the Administration
on Aging (AoA) work together to disseminate research-based consumer
education to the thousands of seniors who participate in the Meals-on-
Wheels program across the Nation. In response, NIA staff, with the
participation of AoA, have conducted focus groups of program managers
from the Meals on Wheels Association of America (MOWAA) to determine
the types of information of greatest interest to MOW's clients, as well
as the best ways to deliver such information (e.g., meal tray liners
printed with key health messages, articles for MOWAA newsletters, or
specially crafted Age Pages.) Based on focus group feedback, NIA is
currently revising Age Pages on diabetes, alcohol, and depression;
these materials will be tested at the upcoming MOWAA meeting in
September 2004, and we anticipate that distribution to MOWAA clients
will begin shortly thereafter.
The Alzheimer's Disease Education and Referral (ADEAR) Center has
been compiling and disseminating information about AD for health
professionals, persons with AD and their families, and the public since
1990. NIA is also working to translate research findings into action
through its highly successful campaign to encourage older people to
exercise. In the last four years, NIA has distributed over 611,000
copies of its exercise guide and 93,000 copies of its companion video
to the public. A Spanish-language version of the guide was published in
January 2002, and over 33,500 copies have been distributed to date. The
NIA's efforts to promote exercise and strength training are conducted
in support of the President's ``HealthierUS'' and the Department of
Health and Human Services' ``Steps to a HealthierUS'' initiatives.
______
Prepared Statement of Dr. Andrew C. von Eschenbach
BUDGET STATEMENT
The fiscal year fiscal year 2005 budget includes $4,870,025,000, an
increase of $134,052,000 over the fiscal year 2004 enacted level of
$4,735,973,000 comparable for transfers proposed in the President's
request.
2015 CHALLENGE GOAL
The Nation's unwavering support of cancer research has enabled the
National Cancer Institute (NCI) and our many partners throughout the
cancer research community to make enormous strides over the past three
decades. Our understanding of cancer as a disease process, and the
associated opportunities to prevent, detect early and successfully
treat it has improved dramatically. However, even in the face of this
progress, the magnitude of the cancer burden means that the disease
still affects nearly every family in America. This year, approximately
1.4 million of our citizens will face a cancer diagnosis, and over
560,000 of our citizens--about 1,540 each day--will die from their
disease. Furthermore, the fact that cancer occurs primarily in
individuals over the age of 50 means that more of our citizens will
suffer the terrible burden of this disease in the next 10-20 years due
to the aging and changing demographics of our population.
Fortunately, the convergence of science and advanced technologies
is changing our perceptions of what is possible. In fact, we are
entering a period in biomedical research where progress in cancer
research can be exponential--an inflection point. Last year I informed
this committee that ``our nation's investment in basic research has
fueled the engine of discovery, which is rapidly illuminating the
cumulative genetic changes and associated molecular mechanisms that
ultimately produce cancer.'' As I said then and I reiterate now ``for
the first time, we have within our grasp the ability to design target-
specific interventions to preempt this process.'' Based on the current
astounding pace of progress in cancer research and the transformational
effects of advanced biomedical technologies, I am even more fervent in
my belief that we can achieve this vision.
To capitalize on this inflection point, I have set forth an
ambitious challenge goal for the NCI, and for the entire cancer
research and care community: to eliminate suffering and death from
cancer by 2015. This ``stretch goal'' is intended to unify and focus
our thinking, strategies, and actions in new ways that will optimize
the use of our resources and accelerate progress against cancer. This
challenge also presents new opportunities for the NCI to provide
leadership for our Nation's effort to conquer cancer, especially in the
development of the new synergies and partnerships needed to achieve
this bold vision.
Recent progress across nearly all of biomedical research has set
the stage for unimagined progress in biomedicine early in the 21st
century. Thanks to research, we now understand that cancer is a disease
process--where normal cells are transformed into cancer cells through a
series of defined steps that begin with a simple change in the genetic
material. If left unchecked, these transformed cells can progress and
spread to cause the suffering and death that we recognize as the
horrific burden of cancer. Thankfully, our growing understanding of
this process has revealed multiple opportunities to intervene. These
new intervention strategies include preventing initiation of the
process; detecting it early when it is most amenable to elimination;
and arresting the process to stop the spread (metastasis), which is the
primary reason that patients suffer unduly and die from their disease.
In short, we are rapidly learning how to ``preempt'' the cancer disease
process. We believe in the next few years that new intervention
strategies will allow us to prevent and/or eliminate many cancers--and
ultimately transform cancer into chronic, manageable diseases that
patients live with--not die from.
Scientific advances and major discoveries from areas such as
genomics, nanotechnology, proteomics, immunology, and bioinformatics
allow us to envision a not too distant future when a patient's genetic,
lifestyle, and environmental risk for cancer can be combined with
effective prevention and early intervention strategies especially for
those at high risk. Serum genomic and proteomic patterns, and advanced
imaging technologies, will be employed to detect cancers at the
earliest stages. Precise molecular diagnosis and patient-specific
prognostic profiling will allow physicians to predict response to
specific interventions and provide a rational basis for tailoring
therapies. The result will be more efficacious and less toxic, targeted
agents delivered to patients. Achieving these outcomes will result in
the preemption of a great deal of cancer. I believe that this is no
longer a dream but an achievable reality.
To achieve the 2015 challenge we must take the steps necessary to
accelerate the pace of progress across the entire cancer research
continuum. The basic research which is aimed at discovering the
pathways that lead to cancer represents the beginning of a continuum
that proceeds through development of new agents and technologies and
ultimately to the delivery of these new interventions to patients.
Using our ever increasing knowledge of the molecular defects in cancer
cells and the biomarkers that define the cancer process will enable the
development of the new targeted interventions we need to prevent,
detect, and treat cancer.
To achieve this acceleration the NCI has identified six ``mission-
critical'' research areas that we believe will offer significant
potential for near term progress against cancer. These include:
harnessing the power of the newly emerging science of molecular
epidemiology to better identify risk populations; developing an
integrative understanding of cancer (systems) biology to discover key
biomarkers and targets; facilitating the development of ``strategic''
cancer interventions for targeted prevention, early detection, and
treatment; creating a national integrated clinical trials system to
more effectively test these interventions; overcoming health
disparities to deliver these advances to those in greatest need; and
developing a bioinformatics network to connect the cancer research
community and optimize the collection, analysis, and use of the
enormous amount of data and knowledge that must be managed and shared.
CANCER BIOMEDICAL INFORMATICS GRID (CABIG)
In this past year's Appropriations Committee Report, NCI was
requested to explore ways in which information could be better shared
among researchers and cancer care deliverers. In early 2004, the NCI
responded by launching an unprecedented program to connect cancer
researchers through an advanced technology platform called the Cancer
Biomedical Informatics Grid (caBIG). This pilot initiative has the
potential to transform the pace of cancer research by providing the
tools needed to share information and data. caBIG will be developed by
connecting 50 of our NCI-designated cancer centers through an NCI-
developed open source system which will in effect become the ``World
Wide Web'' of cancer research. This platform which integrates with the
NIH Roadmap informatics initiative will link individual cancer
researchers and research institutions across the nation, and around the
world, in an open source, federated network that will enable
researchers to share tools, standards, data, computing applications,
and technologies. This unprecedented bioinformatics system will
facilitate the collection, storing, searching, analysis,
classification, management, and archiving and retrieval of research
data. caBIG will improve the quality of data, provide unimagined access
to heretofore limited databases, increase the pace of cancer research
and enhance the effectiveness of our investments in cancer research.
caBIG has the capability to virtualize cancer research.
caBIG leverages the unique resources and capabilities of NCI's
cancer centers to meet the needs of the broad cancer research and care
communities. The cancer centers, along with NCI's platforms for
translational research, the Specialized Programs of Research Excellence
(SPORES), are our partners in this strategic effort to ensure that the
fruits of fundamental scientific research can be rapidly captured for
the benefit of cancer patients. This is an example of how the future
can be transformed if we can successfully integrate advanced
technologies across the discovery, development, and delivery research
continuum. In this instance the whole will be a great deal more than
the sum of the parts.
NATIONAL ADVANCED BIOMEDICAL TECHNOLOGY INITIATIVE
In developing strategies to optimize progress in NCI's high
priority research areas, it became clear that we must proactively
identify, develop, and deploy advanced biomedical technologies, such as
bioinformatics, across the entire cancer research continuum. This
concept represents a critical new element of our overall strategy to
achieve the 2015 challenge goal; however, there is clearly a gap
between our current level of capabilities in advanced technologies and
what is needed. I believe that we now have the opportunity to address
this gap through the creation of an unprecedented national advanced
biomedical technology initiative that will be transformational for
cancer and other diseases.
Achieving our challenge goal will require that we fully integrate
advanced ``enabling'' technologies with the cancer research and care
enterprise. Advanced technologies represent those new tools and
approaches that enable new approaches to the challenging problems of
detecting, controlling, and preventing cancer. Advanced technologies
allow cancer researchers to generate, collect, and analyze vast amounts
of data, and to pursue innovative approaches that could not be
accomplished without these sophisticated tools. As illustrated by our
efforts in bioinformatics, the NCI is providing leadership in the
development and integration of advanced technologies and we are also
building the cross-disciplinary teams needed to implement these new
strategies.
Providing advanced technology platforms to scientists working in
cancer research is one of our highest priorities at the NCI; and to
that end, we have undertaken a cancer-enterprise wide planning effort
to develop a national advanced technology initiative for cancer. In
planning for this initiative, the NCI has identified (in addition to
bioinformatics) multiple areas of advanced technology development that
will be crucial in building this national resource. Examples of cross-
cutting capabilities, which will support the range of strategic
research priorities that we have identified as pivotal areas for
progress, include: advanced imaging; biomarkers and proteomics;
nanotechnology; and development capabilities such as scale-up for new
cancer therapies and prototyping for new diagnostics devices.
We have made significant progress in cancer diagnosis and treatment
based on static imaging of the body's organs provided by x-ray, CT,
PET, and MRI. The new generation of advanced imaging technologies will
target specific molecules and cells. We will be able monitor cellular
processes to assess the effectiveness of experimental treatments and to
define cancer cells at their earliest stages. Nanotechnology will
provide opportunities to develop biosensors that have the capability of
detecting changes in cells at the earliest stages of cancer and
``report'' back on them. This breakthrough technology will also
facilitate the design of new technologies to probe cell functions,
measure cellular events with unimagined precision, and specifically
deliver molecular entities to attack cancer. The combination of
advanced imaging and nanotechnology offers the promise of realizing
these advances to achieve the exponential progress that is possible at
the current inflection point.
The post-genomics era in cancer research has produced vast amounts
of information aout the genetic basis of cancer, but perhaps of more
importance, we are learning that the functioning of normal and tumor
cells is controlled by the proteins that are transcribed from these
abnormal genomes. These proteins, along with genes and other indicators
of the processes and pathways that distinguish cancer, are called
biomarkers. Through the use of advanced technologies NCI is developing
innovative strategies to discover and validate biomarkers for use in
clinical applications. Biomarkers, along with advanced imaging,
nanotechnology, and other advanced technology platforms, will comprise
an unprecedented National Advanced Biomedical Technology Initiative for
Cancer (NABTIc).
This initiative is a major element of our strategy to achieve NCI's
challenge goal to eliminate suffering and death due to cancer by 2015.
The NABTIc would leverage and align the capabilities and resources in
advanced technology development across the nation--and gain strength
from all sectors. Through a network of technology ``nodes'' it would
capitalize on capabilities in our cancer centers and SPORES and
optimize the deployment of NCI's existing strengths in advanced
technologies that currently exist at our Frederick campus. This
initiative is currently being refined and further developed with the
aid of our advisors and partners in the extramural community, and a
plan to purse this concept is under development.
STRATEGIC PARTNERSHIPS
Finally, to implement many elements of our strategic plan, we will
partner broadly With all of the sectors that comprise the cancer
community, including other federal agencies and private industry. The
NCI is an active partner with many federal agencies, including the
Department of Defense, the Veterans Administration, the Centers for
Disease Control and Prevention, the Agency on Healthcare Research and
Quality, and the Centers for Medicare and Medicaid Services. One
partnership that is critically important to optimizing the pace at
which laboratory discoveries progress to become new interventions for
cancer is our alliance the Food and Drug Administration (FDA). Early
last year we created the NCI/FDA Interagency Oncology Task Force to
leverage the expertise of both agencies for the expressed purpose of
streamlining and accelerating the development of preventive,
diagnostic, and therapeutic interventions for cancer. Considerable
progress has already been made in the areas of joint training and
fellowships, developing markers of clinical benefit, improvement in the
overall process of oncology drug development, and creation of a common
bioinformatics platform (caBIG) to improve the organization and
reporting of data from oncology clinical trials. These partnerships are
critical. Each agency, along with the other sectors involved in the
development, commercialization, and delivery of the new inventions we
desperately need to preempt cancer, is a valued partner who can unite
with us to facilitate and speed the overall process.
Last year, I closed by telling members of this committee that we
stand at a pivotal crossroads--a defining moment in this nation's
effort to prevent and cure cancer. Over the past 12 months we charted
the future course forward--through the creation and implementation of
innovative strategies--and have undertaken initiatives that will allow
us to move rapidly toward a day when cancer will become a chronic
disease. What was once a vision is becoming reality through the
combined efforts of researchers and leaders from all sectors, patients
and their families--and so many others. I believe that together we will
realize the economic and human benefits of eliminating the suffering
and death due to cancer, and in this quest, inform our efforts to
transform our overall health care system.
______
Prepared Statement of Dr. Anthony S. Fauci
Mr. Chairman and Members of the Committee: I am pleased to present
the President's budget request for the National Institute of Allergy
and Infectious Diseases (NIAID) of the National Institutes of Health
(NIH). The fiscal year 2005 budget of $4,425,507,000 includes an
increase of $122,467,000 over the fiscal year 2004 enacted level of
$4,303,040,000, comparable for transfers proposed in the President's
request.
NIAID conducts and supports research studies to understand, treat,
and prevent infectious diseases such as HIV/AIDS and other sexually
transmitted infections, influenza, tuberculosis, malaria, and illness
from potential agents of bioterrorism. In addition, the Institute
supports research on transplantation and immune-related illnesses,
including autoimmune disorders, asthma and allergies. For 56 years,
NIAID-sponsored research has led to new therapies, vaccines, diagnostic
tests, and other technologies that have improved the health of millions
of people worldwide. Historically, NIAID has accomplished its mission
with a strong commitment to basic and targeted research in immunology,
microbiology, and infectious disease, disciplines that are related and
complementary. The new initiatives of the NIH Roadmap, and the
information, reagents and infrastructure they will produce, will
further promote the efficient and effective movement of NIAID
discoveries from the laboratory bench to the bedsides of patients.
THE NIAID RESEARCH RESPONSE TO THE THREAT OF BIOTERRORISM
The use of deadly pathogens such as smallpox or anthrax as agents
of bioterrorism is a serious threat to the citizens of our nation and
the world, and biodefense research to mitigate this threat is a key
focus of NIAID research. Since the anthrax attacks of 2001, NIAID has
significantly strengthened, accelerated, and expanded our biodefense
research program. NIAID-supported biodefense research includes: (a)
basic studies of the structure, ecology, and disease-causing mechanisms
of microbes that could be used by bioterrorists; (b) the response of
the immune system to these pathogens, and; (c) the translation of this
knowledge into safe and effective countermeasures--treatments,
diagnostics, and vaccines. To achieve our biodefense research goals,
NIAID works closely with partners in academia, industry, and other
private and public-sector agencies. Research on potential agents of
bioterror promises to enhance not only our preparedness for
bioterrorism, but also for naturally occurring endemic and emerging
infectious diseases.
Progress in biodefense research has been swift and substantial.
More than 50 major NIAID initiatives involving intramural, academic and
industrial partners have been undertaken. As part of this effort, the
Institute has greatly increased biodefense research capacity. For
example, NIAID recently funded eight Regional Centers of Excellence for
Biodefense and Emerging Infectious Diseases Research. This nationwide
network of multidisciplinary academic centers will conduct wide-ranging
research on infectious diseases and the development of diagnostics,
therapeutics and vaccines. In addition, NIAID is supporting the
construction of two National Biocontainment Laboratories (NBLs) and
nine Regional Biocontainment Laboratories (RBLs). These high-level
biosafety facilities promise to speed the development of effective
therapies, vaccines and diagnostics for diseases caused by agents of
bioterror as well as for naturally occurring emerging diseases such as
SARS and avian influenza.
In addition, NIAID has developed and expanded contracts to screen
new drugs; develop new animal models and establish a reagent and
specimen repository. NIAID also has made a significant investment in
determining the genetic sequences of the genomes of a range of
pathogens, which has helped to illuminate the workings of all classes
of microorganisms. NIAID-supported researchers and their international
colleagues have sequenced genomes representative of all bacteria
considered bioterror threats (including multiple strains of the anthrax
bacterium), as well as at least one strain of every potential viral and
protozoan bioterror pathogen. NIAID also is funding research to better
understand the body's own protective mechanisms. A new NIAID program,
the Cooperative Centers for Translational Research on Human Immunology
and Biodefense, will conduct research to better understand the human
immune response to potential agents of bioterror, with the objective of
developing new bioterror countermeasures. Another large-scale program
is funding sophisticated studies of the human innate system, comprised
of the cells that are the ``first responders'' to infection. Boosting
innate immunity holds great promise for developing fast-acting
countermeasures to mitigate the effects of bioterror pathogens or
toxins.
The ultimate goal of all NIAID biodefense research is the
development of medical countermeasures. NIAID-supported scientists have
identified: (a) antivirals that may play a role in treating smallpox or
the complications of smallpox vaccination; (b) several approaches to
blocking the toxins of the anthrax bacterium; as well as (c)
antibiotics, antivirals and antitoxins against other major bioterror
threats. New and improved vaccines against smallpox, anthrax and other
potential agents also are being developed, with the objective of adding
them to the Strategic National Stockpile (SNS). For example, NIAID has
sponsored the development of a next-generation anthrax vaccine known as
rPA, with the goal of adding 75 million doses to the SNS to protect
U.S. citizens. Clinical trials of rPA are ongoing; results to date
build on similar findings in animal studies and suggest that the
vaccine is safe and capable of evoking a robust immune response.
Researchers also will test whether the currently recommended course of
antibiotic therapy for individuals exposed to anthrax spores can be
reduced by vaccinating exposed subjects with rPA.
NIAID-supported researchers also are testing several new smallpox
vaccines that may prove at least as effective as the current smallpox
vaccine, but with fewer side effects. One of these, modified vaccinia
Ankara (MVA), is based on a strain of the vaccinia virus that
replicates less robustly than the traditional Dryvax vaccinia virus,
and is known to cause fewer side effects than the latter. Human trials
of MVA vaccines are underway at NIH and elsewhere. Encouragingly,
recent studies by NIAID intramural scientists and their colleagues have
shown that MVA protects monkeys and mice from smallpox-like viruses.
NIH also has launched the first human trial of a vaccine designed to
prevent infection with Ebola virus. The trial vaccine, a type called a
DNA vaccine, is similar to other investigational vaccines that hold
promise for controlling such diseases as AIDS, influenza, malaria and
hepatitis.
HIV/AIDS RESEARCH
Most recent estimates on the scope of the HIV/AIDS pandemic are
profoundly sobering. Approximately 40 million people worldwide are
living with HIV/AIDS. In 2003 alone, 5 million people worldwide were
newly infected with HIV--about 14,000 each day, more than 95 percent of
whom live in low and middle income countries. In 2003, 3 million people
worldwide with HIV/AIDS died. In the United States, nearly one million
people are living with HIV/AIDS, and by the end of 2002, more than
500,000 people with HIV/AIDS had died. As shocking as these numbers
are, they do not begin to adequately reflect the physical and emotional
devastation to individuals, families, and communities coping with HIV/
AIDS, nor do they capture the huge deleterious impact of HIV/AIDS on
the economies and security of nations, and indeed entire regions. Even
as the burden of HIV/AIDS continues to grow, recent developments
provide some measure of optimism. For example four new antiretroviral
drugs were licensed in 2003 by the U.S. Food and Drug Administration
(FDA), each of which built on NIAID-sponsored research and/or has been
tested in NIAID clinical trials networks. Many other ``next-
generation'' anti-HIV drugs are in clinical trials.
A vaccine that prevents HIV infection--or at least slows the
progression of disease--is a critical NIAID priority. Vaccine
developers face formidable obstacles, including the genetic diversity
of the virus and the lack of a clear understanding of the immune
responses that might protect against HIV infection. Nonetheless, NIAID
and our academic, industrial, international and philanthropic partners
have made significant progress. Numerous HIV vaccine candidates are in
various stages of preclinical and clinical development. The new
Partnership for AIDS Vaccine Evaluation (PAVE) promises to optimize
these efforts. PAVE is a coordinated HIV vaccine research effort that
includes the three government agencies most involved in this activity--
NIH, the Centers for Disease Control and Prevention (CDC), and the
Department of Defense. These agencies will work together to ensure that
research protocols, standards, and measures are developed in a
coordinated and harmonized manner so that outcomes can be compared
across trials in the most cost effective and scientifically efficient
manner. International non-government organizations (NGOs) and companies
also have expressed interest in joining the partnership. Concurrently,
novel approaches to HIV prevention are being studied and validated,
including topically applied microbicides that individuals could use to
protect themselves from HIV and other sexually transmitted pathogens.
As discussed in the new NIAID Strategic Plan for Topical Microbicides,
more than 50 candidate agents have shown laboratory activity against
HIV and other STDs, and several of these agents have demonstrated
safety and efficacy in animal models. In small human studies, several
products have proven safe; later this year, NIAID's HIV Prevention
Trials Network (HPTN), in conjunction with the National Institute of
Child Health and Human Development, will launch a large international
study to test two promising products in more than 3,000 women at high
risk of acquiring HIV in the United States, five African countries, and
India.
RESEARCH ON OTHER EMERGING AND EMERGING INFECTIOUS DISEASES
Infectious diseases have always afflicted humanity, and they will
continue to confront us as long as man and microbes co-exist.
Unfortunately, the viruses, bacteria, and parasites that cause
infectious diseases do not remain static, but continually and
dramatically change over time as new pathogens (such as HIV and the
SARS coronavirus) emerge and as familiar ones (such as influenza virus
and West Nile virus) re-emerge with new properties or in unfamiliar
settings.
West Nile virus (WNV) first appeared in the western hemisphere in
1999, and by 2003 had spread to 45 states in the United States. NIAID
has moved quickly to address this threat with basic research on the
virus and its maintenance in nature, the development of vaccines and
treatments, and the provision of reagents and other resources to the
research community. NIAID also is supporting the development of three
types of vaccines, as well as the screening and testing of WNV
therapies. For example, the NIAID-sponsored Collaborative Antiviral
Study Group is assessing the safety and efficacy of WNV immunoglobulins
in patients with, or at high risk of serious brain diseases caused by
WNV.
Severe acute respiratory syndrome (SARS) is a new infectious
disease first identified in humans in early 2003. The prompt
recognition that SARS is caused by a new type of coronavirus, and the
rapid progress in SARS research reflect the dedication of and
collaboration by the world's medical researchers and public health
experts, including NIAID-sponsored scientists in the United States and
abroad. NIAID supports research to understand the epidemiology and
biology of the SARS virus and how it spreads, and to develop SARS
countermeasures. Several approaches to SARS countermeasures are being
pursued by the NIAID Laboratory of Infectious Diseases, the NIAID
Vaccine Research Center, and by our contractors and grantees. For
example, NIAID is participating in a project to screen up to 100,000
antiviral drugs and other compounds for activity against the SARS
virus, and will test the most promising in animal models and human
clinical trials. A number of compounds have shown promise in the test
tube, including alpha interferon, a drug already approved by the FDA
for the treatment of hepatitis B and C infections.
NIAID scientists and grantees are pursuing several parallel
approaches in the search for a SARS vaccine. Once these experimental
vaccines are ready, NIAID plans to test them in human clinical trials
in our network of Vaccine and Treatment Evaluation Units. New research
suggests that a SARS vaccine is within reach: NIAID intramural
scientists have demonstrated that the mouse immune system develops
antibodies capable of single-handedly neutralizing the SARS virus. This
discovery affirms that researchers developing vaccines that trigger
antibodies to the SARS virus are heading in the right direction. These
findings also indicate that drug researchers can use laboratory mice as
a model to evaluate whether a drug blocks the SARS virus. Both findings
could help lessen the time it takes to develop an effective vaccine or
antiviral drugs for SARS.
Influenza is a classic example of a re-emerging disease; it is not
a new disease, but it continually changes. Because the replication
machinery of the influenza virus is error prone, as the virus
multiplies it can mutate to a slightly different form; this is referred
to an ``antigenic drift.'' Such viruses might require a slight
modification of the yearly influenza vaccine to accommodate these
changes. In addition, non-human influenza viruses such as avian
influenza, can emerge that may be able to jump species into domestic
poultry, farm animals such as pigs, and humans. This type of
significant change in the antigenic makeup of the virus is referred to
as ``antigenic shift.'' Deadly pandemics associated with antigenic
shifts are known to have occurred in 1918, 1957, and 1968. The pandemic
that occurred in 1918-1919 after an antigenic shift killed 20-40
million people worldwide, including more than half a million in the
United States. This recent history explains the current high level of
concern about the appearance of new forms of virulent H5N1 avian
influenza viruses in Asia that can adapt themselves by mutation to
infect humans as has been the case already in dozens of individuals in
Viet Nam and Thailand. Of even greater concern is the possibility that
this avian virus can combine or reassort its genes with a human
influenza virus and acquire the capability of readily spreading from
person to person resulting in a new pandemic. Given the poor condition
of public health systems in many underdeveloped regions and the speed
of modern air travel, the consequences of such an event, should it
result in an influenza pandemic, would be severe.
To address this threat, NIAID supports a broad program to develop
more effective approaches to controlling influenza virus infections.
Research includes programs to understand the pathogenesis,
transmissibility, evolution, epidemiology, and the immune response to
influenza viruses, as well as to develop new diagnostics, antiviral
drugs and vaccines. NIAID currently supports several research projects
to develop vaccines that could be manufactured more rapidly, are more
broadly cross-protective, and are more effective than current influenza
vaccines. The use of reverse genetics--a tool developed by NIAID
grantees--holds the promise for more rapid generation of vaccine
candidates that match the anticipated strain expected to circulate
during the influenza season. Reverse genetics also can be used to turn
highly pathogenic influenza viruses into vaccine candidates more
suitable for vaccine manufacturing by removing or modifying certain
virulence genes; laboratories around the world are using the technique
to prepare vaccine candidates against the H5N1 viruses emerging in
Asia. NIAID also is funding the development of new influenza vaccine
technologies. Recently, NIAID supported a Phase II clinical trial of a
new influenza vaccine produced in a cell culture system as an
alternative to manufacturing the vaccine in eggs. Because NIAID has had
remarkable success in the past with groundbreaking vaccine research--
including advances that led to hepatitis B, Haemophilus influenzae b,
pneumoccocal pneumonia, and acellular pertussis vaccines--we are
confident that one of the approaches that we are pursuing also will
lead to a useful, ``next-generation'' influenza vaccine that can
readily be adapted to emerging influenza strains.
RESEARCH ON IMMUNE-MEDIATED DISEASES
Immune-mediated diseases such as autoimmune diseases, allergic
diseases, and asthma are important health challenges in the United
States and abroad. Autoimmune diseases afflict 5 to 8 percent of the
U.S. population; asthma and allergic diseases combined represent the
sixth leading cause of chronic illness and disability in the United
States, and the leading cause among children. The past two decades of
fundamental research in immunology have resulted in a wealth of new
information and extraordinary growth in our conceptual understanding of
the immune system and the pathogenesis of immune-mediated diseases,
which has led to the development of many useful therapies. For
instance, we now have powerful treatments that selectively target
several of the immune system molecules that cause inflammation, a
hallmark of many autoimmune diseases. NIAID-sponsored researchers are
now developing novel ways of selectively blocking inappropriate or
destructive immune responses, while leaving protective immune responses
intact, an area of research known as tolerance induction. In the Immune
Tolerance Network, a consortium of basic and clinical scientists,
promising studies are underway using tolerance induction to treat
autoimmune diseases, such as rheumatoid arthritis, type 1 diabetes, and
multiple sclerosis; asthma and allergic diseases; and the rejection of
transplanted organs, tissues, and cells. So-called ``tolerogenic''
therapies would replace current lifelong non-specific immunosuppressive
regimens (and their often debilitating side-effects) with short-term
specific regimens that hold the promise of being curative.
Other important research is being conducted by the recently
expanded Autoimmunity Centers of Excellence. The nine centers that make
up this program conduct basic research and clinical trials on new
immune-based therapies for diseases that collectively afflict between
14 and 22 million Americans. The Institute and our collaborators also
have significantly bolstered the study of primary immunodeficiency
diseases--disorders caused by inherited flaws in the immune system that
increase susceptibility to infections--with funding of the Primary
Immunodeficiency Research Consortium (PIRC), a coalition of the world's
most prominent researchers in the field of primary immunodeficiency
diseases.
Another important NIAID research focus is the development of new
interventions to reduce the burden of asthma, a significant and growing
public health problem in the United States and many nations worldwide.
NIAID has long been at the forefront of discoveries leading to the
characterization of asthma and allergic diseases and is now vigorously
pursing the translation of basic knowledge into more effective
treatment and prevention strategies. To develop interventions to
prevent the onset of asthma, more information is needed on the events
that induce asthma. NIAID's Inner-City Asthma Consortium (ICAC) will
soon launch a large study to define and analyze immunological and
environmental influences upon the development of childhood asthma in a
cohort of urban children followed from birth.
CONCLUSION
With a strong research base, talented investigators in the United
States and abroad, and the availability of powerful new research tools,
NIAID anticipates that our basic and applied research programs will
provide the countermeasures to improve our defenses against those who
would attempt to harm us with bioterrorism, will develop new tools in
the fights against HIV/AIDS and other infectious diseases, and will
improve therapies and management of immune-mediated diseases.
______
Prepared Statement of Dr. Nora D. Volkow
Mr. Chairman and Members of the Committee: I am pleased to present
the President's budget request for the National Institute on Drug
Abuse. The fiscal year 2005 budget includes $1.019 billion, an increase
of $28.273 million over fiscal year 2004 conference level of $990.787
million comparable for transfers proposed in the President's request.
NIDA: 30 YEARS OF DISCOVERY
As the National Institute on Drug Abuse (NIDA) prepares to
celebrate its 30th anniversary this year, I am honored to have this
opportunity to tell you about some of our remarkable scientific
accomplishments and how these advances are setting the course for a
better future. A tomorrow that will bring us even better prevention
interventions to deter the initial use of drugs by those at risk before
they become one of the more than 180 million people around the world
who currently abuse illegal drugs. A future that will also bring us
better treatment interventions to help those who have already become
addicted, and who may suffer from some of the myriad consequences of
drug abuse including HIV/AIDS and comorbid mental illnesses. Research
supported by NIDA, the world's largest supporter of research on the
health aspects of drug abuse and addiction, may even bring us
innovative and improved ways to deal with other major health epidemics
impacting our society, such as chronic pain and obesity.
ADDICTION AND OBESITY: COMMON NEUROBIOLOGICAL MECHANISMS
Obesity and addiction are serious National health problems that may
have much in common. Both addiction and some forms of obesity represent
problems resulting from excessive behaviors and lack of impulse
control. Knowledge derived from addiction research shows that the brain
circuits involved in compulsive eating and impulse regulation are part
of the same brain systems involved in addiction, with the
neurotransmitter dopamine playing a prominent role. (See Figure 1.) A
better understanding of the role of the dopamine and other systems in
the motivation for and salience of food may lead us to the development
of better medications and behavioral interventions for obesity, as well
as addiction. In addition, medications being developed for obesity may
also help to reduce drug use. Because of the commonalities between
these disorders, we are able to share knowledge of brain and behavior
and combine efforts across institutes to forge new insights and
approaches that may result in improved health for all. NIDA is pleased
to be a key participant in a trans-NIH initiative that is looking at
all aspects of this chronic health problem, from its neurobiological
underpinnings to helping people establish healthy behaviors.
THE INTEGRATION OF BRAIN, BEHAVIOR AND HEALTH
Understanding the connections between brain, behavior, and health
will be critical to improving the health of ALL Americans. Science is
at a point where all the elements of the human brain (genes, proteins,
circuits) and its development can now be mapped out.
We did it with the Human Genome and I am confident we can do it
with the brain. We are already beginning to unravel how various genes,
proteins, brain circuits and pathways interact with each other and the
environment to affect all aspects of human behavior. This overarching
approach is necessary if we are to make progress in improving the
quality of life for individuals who suffer from complex disorders, such
as drug addiction, which can start at a young age and continue across
the lifespan. Now that advances in medical sciences have increased the
lifespan of humans, a major challenge becomes to improve the quality of
life of individuals, which hinges on our ability to understand the
neurobiological underpinnings of human behavior and the impact and
malleability the environment can have on it. This pertains not only to
problems such as addiction, but other health problems such as obesity,
adherence to medical regimens and with establishing and maintaining
healthy life styles.
ADOLESCENCE, THE DEVELOPING BRAIN, AND PREVENTION
Collaborating with other Institutes to map out structural and
functional aspects of the brain and how it changes throughout
development will help us better understand human behavior, and how we
can modify it to improve and extend human life. In particular,
understanding the developing adolescent brain will be useful in drug
abuse prevention efforts. Research indicates that exposure to drugs of
abuse in adolescence, when many changes are occurring in the brain, may
be a period of significantly increased vulnerability to drugs' effects.
Fortunately, advances in science and NIH-funded studies have now
brought us to a point where our researchers can use new animal models,
new brain imaging technology and other neurobehavioral assessment tools
to probe the development of brain and behavior interactions. These new
directions in adolescent research will help to inform us on important
aspects of cognition, decision-making, emotional regulation, and risk
perception during adolescence, and will help us determine how these
play a role in the use and consequences of illicit drugs. Armed with
new knowledge about how adolescents make decisions, NIDA will be poised
to design interventions that can reduce drug experimentation and
addiction. We are making progress in this regard through our National
Prevention Research Initiative and through our science education
activities like ``NIDA Goes Back to School Campaign'' where science-
based materials were disseminated to teachers and students all across
America.
EXCELLENT NEWS: DRUG USE DECLINES
Some of the best news to a NIDA Director came in December 2003 when
we released the latest data on teen drug use trends. NIDA's long-
standing Monitoring the Future Survey showed an approximately 11
percent decline in illicit drug use over the last 2 years by students
in the eighth, tenth, and twelfth grades combined. (See Figure 2.) The
use of MDMA or Ecstasy decreased by almost fifty percent for the three
grades combined in that same time period Also encouraging was the fact
that tobacco use among this population was the lowest in the 28 year
history of the survey.
NEWS FOR CONCERN: PRESCRIPTION DRUG ABUSE CONTINUES
There was also some disturbing news last year about youth drug use,
showing very high rates of abuse of prescription pain killers (e.g.,
Vicodin and OxyContin). Remarkably, 1 in 10 twelfth graders reported
abusing Vicodin last year, making it the second most widely abused
illicit substance after marijuana in this population. Hospitals are
also seeing more patients coming to emergency rooms for prescription
drug abuse. According to data from SAMHSA, between 1994 and 2001 the
number of emergency room mentions for hydrocodone and oxycodone
increased 131 percent and 352 percent respectively. When used as
prescribed, medications like Vicodin can be very effective, but when
used improperly they can have very serious adverse health consequences
including death from overdose. More research is needed to prevent,
educate, and treat prescription drug abuse. Developing new medications
that have no abuse or diversion potential is a high priority for NIDA.
Researchers are making progress in this area. Just last year,
researchers developed a compound to selectively affect a cannabinoid
receptor that is involved in regulating pain. Unlike many other
receptors, this one is not found in the brain. When the compound
(AM1241) was given to animals, they were less sensitive to several
forms of painful stimulation. Not only does this research open up a new
arena for pain medication development, but it also sets the stage for
developing new medications that are less likely to be abused. Also,
NIDA's investment in the development of buprenorphine/naloxone for
treating opioid addiction, for example, provides an alternative
medication for pain that has less diversion potential than that of
other opiate analgesics, and exemplifies how science can help alleviate
our Nation's problems.
RESEARCH ON THE CONSEQUENCES OF MARIJUANA, AND THE DEVELOPMENT OF NEW
MEDICATIONS
Research continues to shed new light on the deleterious
consequences of marijuana, the most abused illegal drug in the United
States. Early exposure to marijuana, for example, has been found to
increase the likelihood of a lifetime of subsequent drug problems. A
recent study, published in the Journal of the American Medical
Association of over 300 fraternal and identical twin pairs, who
differed on whether or not they used marijuana before the age of 17,
found that those who had used marijuana early had elevated rates of
other drug use and drug problems later on, compared to their twin who
did not use marijuana before age 17. This study re-emphasizes the
importance of primary prevention by showing us that early drug
initiation is associated with increased risk of later drug problems,
and it provides more evidence for why preventing marijuana
experimentation during adolescence could have a big impact in
preventing addiction.
We are also finding that a lifetime of heavy cannabis use can
result in an overall dissatisfaction with oneself and with life for
most users. Last year, researchers published data on the impact of
long-term cannabis use on life achievement such as educational
attainment and income. Significantly fewer of the heavy cannabis users
completed college and more had household incomes of less than $30,000
compared to individuals who used marijuana minimally.
It is clear, more research is needed to curtail use of this drug.
Although the number of marijuana treatment admissions has increased
from 92,414 in 1992 to 255,394 in 2001, there are relatively few
treatments that have been shown to be effective specifically for
marijuana addiction. NIDA is encouraging researchers, as well as the
pharmaceutical industry, to become more active in finding new
medications for marijuana and for other drugs of abuse. With the fairly
recent discovery of an endogenous cannabinoid system with specific
receptors and endogenous ligands, the likelihood of finding new targets
for medications development is increased. One form of a cannabinoid
receptor antagonist (CB1-receptor) has already been developed by
several pharmaceutical companies and is undergoing clinical
investigation for the treatment of alcoholism and nicotine addition, as
well as obesity. Moreover, preliminary data in humans has shown that it
can block the effects of marijuana.
ACCELERATING RESEARCH DISCOVERIES BENCH TO BEDSIDE: BEDSIDE TO
COMMUNITY NIH ROADMAP AND OTHER INITIATIVES
For science to be useful in preventing and treating addiction this
knowledge has to reach the communities. This is an area where NIDA
continues to excel. Over the past few years, NIDA has established and
strengthened strong collaborative relationships with a number of
government agencies, including the Substance Abuse and Mental Health
Services Administration (SAMHSA) to build national infrastructures that
can facilitate the flow of research into community practice. NIDA's
National Drug Abuse Treatment Clinical Trials Network (CTN), which now
serves 27 states plus the District of Columbia and Puerto Rico, and the
more newly established National Criminal Justice Drug Abuse Treatment
Study (CJ-DATS) exemplify NIDA's commitment to bringing science out of
the laboratory and to the community. These initiatives parallel and
complement those proposed as part of the NIH Roadmap, including the
promotion of interdisciplincary research and the development of
improved infrastructures for clinical research, which aim to accelerate
the advancement of research discoveries from the bench to the bedside
and to the community.
GETTING THE MEDICAL COMMUNITY MORE INVOLVED IN SCREENING AND ADDRESSING
HIV/AIDS AND OTHER DRUG ABUSE CONSEQUENCES
Because drug abuse begins in youth and most pediatricians and
family physicians typically do not ask questions about drug use, NIDA
has launched a Primary Care Outreach Initiative to educate
pediatricians and other primary care physicians about the importance of
early detection and treatment. The medical community is also being
reminded of the need to recognize substance abuse and addiction as
disorders that will affect the course of other diseases, including
mental illness, cancer, cardiovascular and pulmonary diseases, trauma
and infectious diseases. Injection drug use has directly and indirectly
accounted for more than one-third (36 percent) of AIDS cases in the
United States. Data show that drug abuse treatment can reduce
activities related to drug use that increase the risk of getting or
transmitting HIV. Also the fact that the health and social consequences
of drug abuse, including HIV/AIDS, disproportionately affect racial and
ethnic minority populations; for example almost half of HIV/AIDS cases
occur in African Americans even though they constitute only 11 percent
of the population according to the latest Census data, which highlights
the urgency to conduct research that can benefit all populations. (See
Figure 3.)
Using our established networks (CTN and CJ-DATS), NIDA is
strengthening its commitment to attend to associated health problems
like HIV/AIDS, hepatitis and co-morbidity that often accompany
substance use. The CTN, for example has a number of treatment protocols
underway that address HIV/AIDS and hepatitis. Also, because data
suggest that the prevalence of HIV and other infectious diseases is
high among drug users in the criminal justice system, with HIV
seropositivity rates estimated to be 8-10 times higher than in the
general population, NIDA is encouraging more research to prevent and
treat the spread of HIV/AIDS and other diseases among individuals in
the criminal justice system with substance abuse related problems.
CONCLUSION
Our Nation's investment in drug abuse research is showing
reductions in drug abuse rates and its deleterious consequences at the
individual, family, and community level. A continued commitment to
medical research, and to working with other agencies and sectors, will
lead to new advances, technologies and innovations that will result in
a healthier population.
Prepared Statement of Dr. Jeremy M. Berg
Mr. Chairman and Members of the Committee, good morning. I am
pleased to present the President's budget request for the National
Institute of General Medical Sciences (NIGMS). The fiscal year 2005
budget includes a sum of approximately $1,960 million which reflects an
increase of $55 million over the fiscal year 2004 enacted level of
$1,905 million.
CROSS-CUTTING AND CUTTING-EDGE RESEARCH
Both before joining NIGMS as its new director last November and
since then, I have been tremendously impressed by the Institute's
leadership in supporting basic biomedical research--that is, scientific
studies into the most fundamental biological processes that govern
human health. The kinds of research that we fund are both cross-cutting
and cutting-edge. NIGMS-supported studies have shed light on everything
from the three-dimensional structures of individual proteins--life's
building blocks--to the complex interactions between molecules inside
cells. More importantly, by uncovering the previously hidden workings
of this cellular machinery, not only do we gain a better understanding
of the very basis of human health, but we also gain valuable clues to
fixing this machinery when it goes awry. Those clues are essential in
helping scientists develop better methods to diagnose, treat, and even
prevent a wide range of human diseases.
NIGMS has a successful track record of supporting the nation's
brightest minds in basic biomedical science. Perhaps the highest
recognition of that success can be seen in the number of Nobel Prizes
that NIGMS grantees have won over the past four decades: a remarkable
55 to date. This past year was no exception. Roderick MacKinnon, M.D.,
a biophysicist at the Rockefeller University and a long-time NIGMS
grantee, won the 2003 Nobel Prize in chemistry for discovering the
structure and function of membrane ion channels--the ``gatekeepers''
that control what essential molecules move in and out of cells.
MacKinnon's breakthrough provides direct visualization of the basis for
the electric circuits that are responsible for the functioning of our
brains and the beating of our hearts. The detailed structural
information is revealing how local anesthetics work and why some drugs
have life-threatening cardiac side effects. The work of literally
thousands of other researchers has been redirected in response to his
discoveries.
NIGMS' impressive return on investment in basic biomedical research
is also evidenced by the many other prestigious awards honoring our
grantees. In 2003, Rockefeller researcher C. David Allis, Ph.D., won
the third annual Wiley Prize in the Biomedical Sciences for his work on
chromatin, the complex of DNA with proteins that packages genetic
information inside each cell nucleus. The structure of chromatin is
largely responsible for why one cell is a nerve cell while another cell
is a muscle cell, even though they contain exactly the same DNA
sequence. Allis' studies of the chemical modifications that regulate
chromatin hold promise for learning how to control genes that suppress
and inhibit the growth of tumors in cancer. The previous year, two
other NIGMS grantees--Andrew Z. Fire, Ph.D., of the Stanford University
School of Medicine, and Craig C. Mello, Ph.D., of the University of
Massachusetts Medical School--were among the winners of the second
annual Wiley Prize for their groundbreaking discovery of gene silencing
by a mechanism called RNA interference. The phenomenon of RNA
interference is the subject of upcoming meetings at both the National
Academy of Sciences and NIH because of its potential impact for both
basic research and for entirely novel approaches to preventing and
treating disease.
Even greater advances in biomedical science are possible in the
years to come. Through forward-thinking programs designed to foster
innovative research and train the next generation of pioneering
scientists, NIGMS is playing a leading role in the NIH Roadmap for
Medical Research--the exciting new vision of the future recently
launched by NIH director Elias Zerhouni, M.D. I would like to share
with you some of the key strategies we have developed to help realize
this important vision.
BLAZING A TRAIL FOR THE NIH ROADMAP
Throughout its history, NIGMS has helped push back the frontiers of
medical knowledge primarily by funding the most promising research
grant applications submitted by both new and established scientists.
This so-called investigator-initiated research--supported through the
NIH's R01 grant mechanism continues to be the most important instrument
NIGMS has to promote experimentally based, hypothesis-driven research--
the heart of our nation's scientific mission.
In recent years, NIGMS launched a number of larger, targeted
initiatives to address both significant opportunities and critical gaps
in biomedical research today. In many ways, programs such as NIGMS'
Protein Structure Initiative (PSI), its large-scale collaborative
``glue grants,'' and its new Center for Bioinformatics and
Computational Biology have blazed a trail for the NIH Roadmap. Today,
NIGMS is well positioned to participate with other NIH institutes in
transforming the nation's biomedical research capabilities and
accelerating the translation of scientific discoveries from the bench
to the bedside.
Structural biology is part of the Roadmap's New Pathways to
Discovery theme, and NIGMS is playing a key role in this area. One
major activity is the PSI, an ambitious 10-year project launched in
2000. The aim of the PSI is to solve the three-dimensional structures
of thousands of proteins experimentally and ultimately produce
computer-based tools for modeling the 3-D structure of any protein from
its genetic spelling, or sequence. Knowing the structures of proteins
helps scientists understand how these molecules function in health and
disease and aids in the development of new medicines.
Results from the nine pilot centers set up in the first phase of
the PSI are promising, demonstrating that automated protein production
``factories'' are feasible and are yielding high-resolution data that
is already being used by scientists around the world. This year, NIGMS
plans to ramp up the PSI in its second phase, with the funding of
large-scale centers that will dramatically reduce the time and cost of
solving protein structures, as well as specialized centers that will
tackle challenging problems such as membrane proteins and protein
complexes.
NIGMS is also contributing substantially to Roadmap-related
initiatives through its support of research aimed at unraveling the
complexities of living systems. In 2003, the Institute awarded its
fifth glue grant, bringing together a diverse team of scientists to
assemble a complete picture of lipids--fats and oils--inside cells, and
the role they play in heart disease, arthritis, and other major
illnesses. Other ongoing glue grants awarded since the program started
in 2000 include projects aimed at understanding cellular signaling and
communication, cell movement, and inflammation and the way the body
responds to injury.
Last year, NIGMS also added two new Centers of Excellence in
Complex Biomedical Systems Research. At these centers,
interdisciplinary teams of researchers from both the biological and
physical sciences will focus on the emerging field of ``systems
biology,'' which seeks to find hidden patterns of biological
interactions at all levels, from individual proteins to entire
organisms. The new centers join two others launched the previous year
with NIGMS funding.
COMPUTER-BASED SOLUTIONS TO BIOMEDICAL CHALLENGES
Harnessing the power of computers to solve complex problems in
biology is another major theme in both the NIH Roadmap and NIGMS'
research mission. In 2003, the Institute's recently created Center for
Bioinformatics and Computational Biology welcomed its first director,
Eric Jakobsson, Ph.D., a leading researcher in the field from the
University of Illinois at Urbana-Champaign. Dr. Jakobsson has been
instrumental in launching one of the first Roadmap initiatives, a
program to fund the creation of NIH National Centers for Biomedical
Computing. The centers will bring together computer scientists,
biomedical researchers, and experts from the experimental, clinical,
and behavioral sciences to tackle such challenges as developing
computer simulations that will accurately model the complex inner
workings of the human brain and other vital systems.
One of the most exciting prospects for computational biology is the
promise of turning the vast amounts of data generated by the Human
Genome Project into promising new medical treatments that are tailored
to the individual. As Allen D. Roses, M.D., senior vice-president of
genetics research at GlaxoSmithKline, recently observed, ``The vast
majority of drugs--more than 90 percent--only work in 30 to 50 percent
of the people.'' NIGMS is addressing this critical issue through the
Pharmacogenetics Research Network, a nationwide collaboration of
scientists from academia, government, and industry that the Institute
spearheaded in 2000, with additional funding from five other NIH
institutes. The network has already produced a key computer-based
resource that scientists are now actively using: the Pharmacogenetics
and Pharmacogenomics Knowledge Base (PharmGKB). With this and other
tools at their disposal, scientists will be able to study the effect of
genes on people's responses to a wide variety of medicines including
antidepressants, chemotherapy, drugs for asthma and heart disease, and
many others. The ultimate goal of pharmacogenetics research is to help
tailor medicines to people's unique genetic make-ups, thus making
medicines safer and more effective for everyone.
Computational biology is also at the heart of another NIGMS
initiative: the Models of Infectious Disease Agent Study (MIDAS). An
integral component of the overall NIH biodefense plan, MIDAS is a
network of scientists who will produce user-friendly computational
models for policymakers, public health workers, and other researchers
to assist them in making better-informed decisions about emerging
infectious diseases. The first centers funded through the MIDAS
initiative will launch this year and are expected to contribute
significantly to our ability to prevent, detect, and respond to new
infectious diseases, either natural or human-made.
Other NIH Roadmap-related initiatives include NIGMS' program to
establish high-quality chemical libraries that provide scientists with
powerful tools for discovering potential new drugs, and a portfolio of
grants designed to stimulate the development of new molecular imaging
technologies that can be harnessed to visualize the actions of
individual molecules over time in living cells. The effort to create,
distribute, and apply these tools will be tremendously enhanced by
initiatives that are part of the Roadmap.
TEAM SCIENCE AND INTERDISCIPLINARY TRAINING
The increasingly complex nature of biomedical research today
demands new approaches to carrying out the scientific enterprise. NIGMS
has been at the forefront of addressing this issue, especially in its
support for ``team science''--interdisciplinary research that seeks to
combine the skills and expertise of scientists from diverse fields and
backgrounds. And now as part of another major theme in the NIH
Roadmap--Research Teams of the Future--NIGMS is bringing its own
experience to the table to help build successful synergies in large-
scale research collaborations, and to help prepare the next generation
of biomedical scientists trained in multiple disciplines.
For example, NIGMS has led the way in supporting cross-disciplinary
research and training through its Medical Scientist Training Program--
which leads to the combined M.D.-Ph.D. degree and produces
investigators who can bridge the gap between basic and clinical
research. Other NIGMS programs support training in the cellular,
biochemical, and molecular sciences; systems and integrative biology;
the pharmacological sciences; genetics; molecular biophysics;
biotechnology; the chemistry-biology interface; and bioinformatics and
computational biology.
Many NIGMS research and training programs combine both the
biological sciences--cellular and molecular biology, genetics--and the
quantitative sciences--physics, chemistry, engineering, mathematics.
Indeed, bringing together these two scientific cultures is essential if
we are to continue to make important advances in biomedical research in
the 21st century. That growing realization has spurred a flurry of
activity in recent years. For example, NIGMS joined forces with the
National Science Foundation in 2002 to launch an initiative to
encourage the use of mathematical tools and approaches to study
biology. NIGMS is also partnering with the NIH Office of Science
Education on a program to transform undergraduate biology education by
incorporating examples and perspectives from the quantitative sciences
into biology courses. This program responds to the National Research
Council's Bio2010 report.
NIGMS also has a long-standing commitment to increasing the number
of underrepresented minorities engaged in biomedical research. Through
our Division of Minority Opportunities in Research, NIGMS takes a
leading role at NIH to encourage and prepare minority students to
pursue training for scientific careers and to enhance the science
curricula and faculty research capabilities at institutions with
substantial minority enrollments. Both these programs and the efforts
to train and recruit more scientists from the physical sciences into
biomedical research are essential if we are going to have the
biomedical workforce necessary to solve the challenging problems that
lead to human disease and drive up the costs of providing health care.
BALANCING LARGE- AND SMALL-SCALE SCIENCE
As promising and worthwhile as these major initiatives are, we must
not lose sight of NIGMS' mainstay over the past four decades:
investigator-initiated research. By encouraging the best and brightest
basic scientists to pursue new directions in their fields, NIGMS has
made tremendous contributions to advancing biomedical science. It is
often a single investigator, supported by a single grant, who discovers
something that turns out to be the tip of a very important iceberg. And
we must continue to support these creative minds in order to sow the
seeds for tomorrow's advances.
At the same time, we must recognize the need to invest
strategically in targeted, larger-scale research to meet the critical
needs of ensuring the nation's health and well-being, its technological
competence and competitiveness, and its security. In short, we need to
balance small- and large-scale science in a way that both catalyzes and
capitalizes on innovation. With our experience in managing thousands of
individual research grants every year along with a growing number of
multi-institutional, multidisciplinary research efforts, NIGMS can
strike that balance while leaving open the door to future directions
that are still beyond our powers of prediction.
Thank you, Mr. Chairman. I would be pleased to answer any questions
that you may have.
______
Prepared Statement of Dr. Story C. Landis
Mr. Chairman and Members of the Committee, I am Story Landis,
Director of the National Institute of Neurological Disorders and Stroke
(NINDS). I am pleased to present the President's budget request for
NINDS for fiscal year 2005. The fiscal year 2005 budget includes
$1,546,623,000, an increase of $44.9 million over the fiscal year 2004
enacted level of $1,500,693,000 comparable for transfers proposed in
the President's request.
The mission of the NINDS is to reduce the burden of neurological
disorders by finding ways to prevent or to treat these diseases. When I
began as Director about six months ago, one of my first priorities was
to meet with voluntary groups representing patients and their families.
So far, I have met with more than 40 groups, and this remarkable
experience has educated me about the extraordinary range of diseases
within the NINDS mission, the power of their impact, and the urgency of
finding ways to prevent or treat these disorders. These discussions
also reinforce the importance of increasing public-private
partnerships, which is a goal of our Institute, as well as a major
focus of the NIH Roadmap process.
My own research has focused on fundamental questions about how the
nervous system develops how genes help wire up connections in the
brain, how cells choose to become a particular type, and whether there
is any ``plasticity'' in this process. Issues such as these, long
central to basic neuroscience research, are now at the crux of efforts
to devise treatments for neurological diseases. I am encouraged by the
prevention and treatment strategies emerging from the investment in
basic research drugs to home in on the molecules that cause disease,
stem cells to repair the damaged nervous system, natural neurotrophic
factors to promote survival and growth of brain cells, ``vaccines'' to
prevent stroke, implantable stimulation devices to compensate for brain
circuits unbalanced by disease, therapies to turn off, repair or
replace defective genes, neural prostheses to read control signals
directly from the brain, and behavioral and drug interventions to
encourage the ``plasticity'' of the brain and spinal cord to compensate
for damage. The NINDS must continue to support basic research. We must
also re-energize our efforts to translate opportunities into practical
therapies. Today I will highlight a few of the ways we are working to
bring people and resources together to accomplish that.
STEM CELLS
Neural stem cell biology is one area in which basic science and
clinical promise are so closely intertwined that it is easy to forget
the origins of our understanding of neural stem cells in very basic
research. The generation of new neurons in the adult brain was
discovered when a basic scientist sought to understand how male
canaries learn a new song each spring. This year, NINDS researchers
have contributed to advances in identifying and isolating adult neural
stem cells, in understanding the signals that control embryonic and
adult neural stem cells, and in developing stem cell therapies in
animal models that show promise for Parkinson's disease, demyelinating
diseases, such as Canavan, Krabbe, or Tay-Sachs, and many other
disorders. The NINDS has helped foster research on embryonic and adult
stem cells through several initiatives, including training programs in
the use of approved human embryonic stem cells, grant supplements to
compare these to cells from other sources, and scientific workshops. An
NINDS intramural researcher also leads a new NIH facility that is
characterizing the approved human embryonic stem cell lines. For the
coming year, an initiative targeting collaborative research in stem
cell biology, designed to bring together teams of experts from several
areas of stem cell biology, is a high priority.
GENES AND THE NERVOUS SYSTEM
Genetics is another neuroscience research area that has made
astonishing progress. Overall, researchers have identified more than
200 genes that can cause neurological disorders. Gene findings in the
past year are relevant to diseases such as Parkinson's disease,
Charcot-Marie-Tooth disorder, and cerebral cavernous malformations,
which can predispose people to strokes. Discoveries such as these lead
to improved diagnosis, development of animal models, and the first
clues to what underlies disease processes and how to stop them.
Several NINDS efforts bring people and resources together in
genetics. Some are simple, but important, such as programs to promote
sharing of transgenic mice that are essential models of human diseases.
Others are more ambitious, such as the Gene Expression Nervous System
Atlas (GENSAT) project, which will map the activity of thousands of
genes in the brain and provide genetically engineered mouse strains
that allow scientists to study how these genes contribute to health and
disease. Microarray screening centers make another new technology and
the data arising from it widely available. Microarrays allow scientists
to simultaneously monitor the activity of virtually all genes, with
wide potential applications to basic and clinical neuroscience; for
example, recent studies show micrarrays may predict which patients will
respond to approved drugs for multiple sclerosis. The NINDS Human
Genetics Resource Center, established this year, makes DNA samples,
immortalized cell lines, and accompanying clinical and pedigree data
available to all qualified researchers. The repository currently
contains samples related to stroke, epilepsy, Parkinson's disease, and
motor neuron diseases, including amyotrophic lateral sclerosis (ALS)
and spinal muscular atrophy (SMA).
TRANSLATIONAL RESEARCH
``Translational research'' encompasses the many steps that are
needed to move from basic research insights to a therapy that is ready
for human testing in clinical trials, and the NINDS has a long history
of programs in this arena. For example, over three decades, the Neural
Prosthesis program has supported research on electronic and mechanical
devices that help compensate for abilities lost through disease or
injury, including pioneering research on direct brain control of
prostheses, which has recently become a focus of such forward thinking
agencies as the Defense Advanced Research Projects Agency (DARPA). The
NINDS has responded to increasing opportunities by developing a
comprehensive translational research program that fosters cooperative
efforts, provides peer review criteria tailored to the needs of
translational research, and utilizes milestone driven funding, which is
common in industry. In fiscal year 2003, the Institute funded the first
projects in this program, focused on gene and stem cell therapies for
Parkinson's disease, neuroprotectants for stroke and trauma, treatments
for brain tumor, and drugs for epilepsy, ALS and Huntington's disease.
DRUG DEVELOPMENT FOR NEUROLOGICAL DISORDERS
New and expanding efforts to develop drugs complement the broad
translational program. The NINDS has awarded a contract for a high
throughput screening (HTS) facility, and solicited proposals for the
development of disease-related screening tests. HTS uses robotics to
rapidly test large numbers of chemicals to find lead compounds for drug
development and use as research tools. Ongoing screening efforts focus
on ataxia telangiectasia, ALS, and Parkinson's disease. Several NIH
institutes are working together to develop chemical libraries focused
on the brain, and the NIH Roadmap ``Molecular Libraries'' component
will directly facilitate screening efforts such as these.
Another NINDS drug development effort is a longstanding public-
private partnership. Since 1975, the NINDS Anticonvulsant Screening
Project has worked with more than 140 companies and 230 academic
institutions to test more than 20,000 compounds for anti-convulsant
properties, including several drugs now in clinical use. Guided by the
epilepsy benchmarks planning process, the Institute is expanding this
program with increased focus on preventing the development of epilepsy
and on treatment-resistant epilepsy. The NIH Roadmap ``Structural
Biology'' goals to improve our understanding of membrane proteins, such
as ion channels that are implicated in some types of epilepsy and
neurotransmitter receptors that are often the targets for drugs, will
have an important impact on future efforts to develop drugs for this
and many other neurological disorders.
Some drugs developed for epilepsy have shown promise for other
diseases, such as chronic pain. To take advantage of that kind of
crossover, observed in many areas of medicine, the NINDS worked closely
with academia and voluntary disease organizations to develop a
consortium of 26 laboratories to screen a set of 1,040 known drugs,
mostly approved by the U.S. Food and Drug Administration (FDA) for
other uses, for potential use against neurodegenerative diseases. The
Consortium is sharing data on 29 laboratory screening tests based on
molecules, cells in culture, or simple organisms. Several promising
drugs have moved to further testing in animals, and a few may move soon
to clinical trials.
PROGRAM TO ACCELERATE THERAPEUTIC DEVELOPMENT FOR SMA
Valproic acid is one example of a drug, now used for the treatment
of epilepsy, that in the past year has shown promise in cell culture
for a different disease, spinal muscular atrophy (SMA). SMA is the most
common single gene cause of infant mortality. In recent years,
scientists have discovered the gene defects that cause SMA, developed
animal models that mimic essential aspects of the human disease, and
devised plausible strategies for developing therapies. Because of the
impact of SMA and the state of the science, the NINDS chose this
disease as the focus of an innovative approach, initiated in fiscal
year 2003, to expedite the development of therapies. The performance-
based contract mechanism accelerates all steps from recognition of a
research need, through solicitation and review, to funding of targeted
research subprojects, with guidance by an expert steering committee
that takes a very active role in driving the process. If successful,
this approach might be applied to other diseases.
MUSCULAR DYSTROPHY AND CENTERS PROGRAMS
The muscular dystrophies are another group of inherited disorders
that are a high priority for NIH. Researchers, beginning more than a
decade ago, have identified defects in several genes that can cause the
various kinds of muscular dystrophy. These findings have brought
improved understanding of what causes these diseases, better animal
models to develop therapies, and some practical benefits for example, a
new diagnostic test for Duchenne muscular dystrophy will eliminate the
need for painful muscle biopsy in many children, and help identify
female carriers of the disease before they pass it on to their sons.
Therapies to slow or stop muscular dystrophies have been elusive, but
there have been encouraging results recently in animals using drugs,
stem cells, and gene therapy approaches. To expedite progress against
the muscular dystrophies, the NIH has funded three Senator Paul D.
Wellstone Muscular Dystrophy Cooperative Research Centers, with the
expectation that up to three more will be funded competitively in
fiscal year 2005. The NIH is also working together with the broadly
representative interagency Muscular Dystrophy Coordinating Committee
(MDCC) on developing a muscular dystrophy research and education plan
for NIH.
The NINDS, often working with other components of NIH, has several
centers programs, such as the Morris K. Udall Parkinson's Disease
Centers of Excellence, the Specialized Programs of Translational
Research in Acute Stroke (SPOTRIAS), the Studies to Advance Autism
Research and Treatment (STAART), and the Specialized Neuroscience
Research Program (SNRP), which encourages minority scientists and
addresses health disparities in neurological disorders. Other centers
focus on disorders such as brain tumor, spinal cord injury, and head
trauma.
CLINICAL TRIALS
The NINDS continues to set standards of quality and innovation in
clinical trials that evaluate whether potential treatments or
preventive measures are safe and effective. One recent example, the
Neuroprotection Exploratory Trials in PD (NET-PD), was launched in
April 2003 to evaluate drug therapies that might slow the progression
of Parkinson's disease. The project rigorously selected candidate drugs
from a broad array of potential compounds identified by working with
clinicians and researchers throughout academia and industry. The 42
clinical sites have recruited individuals with early, untreated
Parkinson's, and early phase trials of four drugs will be completed in
early 2005. In the coming year, the NINDS clinical trials program is
also working to train researchers to conduct clinical trials and to
develop a broad clinical trials network that will encompass the greater
community of neurologists. Clinical trials for neurological disorders
is another area in which the cross-cutting NIH Roadmap efforts for
``Re-engineering the Clinical Research Enterprise'' are likely to have
a major impact.
INTRAMURAL PROGRAMS
Before becoming the director of NINDS, I led the Institute's
intramural program on the NIH campus in Bethesda, MD, which is one of
the largest basic and clinical neuroscience programs in the world. In
addition to recruiting superb individual scientists in fields such as
ion channels, genetic diseases of the nervous system, brain tumors, and
stroke, a central focus of the program has been to bring researchers
together from disparate fields of science. To this end, the Porter
Neuroscience Research Center, opening its first phase in 2004, brings
together scientists from eight institutes to ``put the brain back
together'' by overcoming artificial disciplinary boundaries within and
across institutes and by setting the standard for collaborative
research in neuroscience.
FUTURE COOPERATIVE EFFORTS
I have mentioned a few areas in which the NIH Roadmap efforts will
facilitate our efforts against neurological diseases, but the same can
be said of virtually every major effort within the Roadmap. Driven by
the science, several NIH components that have a major focus on the
brain are also increasingly working together to form a ``blueprint for
the brain,'' in which cooperative efforts across Institutes can
expedite progress. These Institutes already cooperate extensively in
areas such as training of researchers, genetics, autism, muscular
dystrophy, health disparities, brain tumors, stroke, and pediatric
neuroimaging, to name a few examples. I hope to report to you in the
future about progress in forming other cooperative ventures aimed at
our common goal of finding better ways to prevent or to treat all
disorders that affect the brain and other parts of the nervous system.
Thank you, and I would be pleased to answer questions.
______
Prepared Statement of Dr. Stephen E. Straus
Mr. Chairman and Members of the Committee: I am pleased to present
the President's fiscal year 2005 budget request for the National Center
for Complementary and Alternative Medicine. The fiscal year 2005 budget
includes $121.1 million, an increase of $4.2 million over the
comparable fiscal year 2004 appropriation of $116.9 million.
INTRODUCTION
Five years ago, recognizing the increasing public health
opportunities of complementary and alternative medicine (CAM) and the
challenges to research in this area, Congress elevated the NIH Office
of Alternative Medicine to the National Center for Complementary and
Alternative Medicine (NCCAM). Several months later, as NCCAM's first
Director, I articulated a set of priorities for the Center that
emphasized growth in the portfolio of rigorous research project grants,
enhanced investments in research training and careers awards to build
an effective CAM research collective, creation of an intramural
research program (IRP), and commitment of stable funding for research
centers. As we embark on planning our second 5 years of work, I am
pleased to report that NCCAM has achieved these and many other critical
objectives.
NCCAM's success to date is evident in some of its vital statistics:
--Under the President's proposed fiscal year 2005 budget, NCCAM's
investment in research project grants will have increased from
approximately $10 million in 1999 to almost $76 million, while
funding for research training and career awards will have
increased from under $1 million in 1999 to approximately $8.8
million.
--In collaboration with other NIH Institutes and Centers (ICs), NCCAM
has launched nine multi-center Phase III clinical trials of
popular CAM interventions for chronic illnesses that affect so
many Americans, including osteoarthritis, dementia, cancer, and
coronary artery disease.
--NCCAM established an intramural research program in 2001, which
studies CAM approaches to diseases of aging, including
arthritis, depression, muscle wasting, cancer, pain, and
diabetes.
--Based on a comprehensive external review, NCCAM refined its
research centers program to support rigorous investigations at
both traditionally research-intensive and CAM institutions. In
2003, NCCAM made its first round of revised center awards in
three categories: Centers of Excellence for Research on
Complementary and Alternative Medicine, Developmental Centers
for Research on Complementary and Alternative Medicine, and
Planning Grants for International Centers for Research on
Complementary and Alternative Medicine. NCCAM's Centers program
will foster capacity in CAM research, catalyze more effective
and essential partnerships between CAM institutions and
research-intensive universities, and facilitate the integration
of effective CAM therapies with conventional medical
approaches.
Already, the nearly 800 projects that NCCAM has supported since
1999 have yelded over 700 scientific publications, including some that
were published in the most prestigious journals--Journal of the
American Medical Association, New England Journal of Medicine, and
Proceedings of the National Academy of Sciences. Complementing these
research and research training activities are extensive efforts to
communicate research results and other critical information about CAM
to the public and practitioners. NCCAM's award-winning Web site is
visited over 1.5 million times each year for its 90 fact sheets,
consumer alerts, news releases, and announcements of new research
initiatives. In a partnership with the National Library of Medicine,
NCCAM helped create a CAM subset on the reference database PubMed that
now hosts nearly 400,000 reports about CAM studies, which are available
to anyone with Internet access. In the aggregate, the investments made
in NCCAM's first 5 years are already informing the health care
decisions Americans make at home and in consultation with their
practitioners.
In its first 5 successful years, NCCAM has become fully integrated
within the NIH, developing a research agenda that is responsive to its
mission, fiscally accountable, and supportive of rigorous CAM research.
NCCAM's research priorities today encompass six thematic areas in which
CAM can have a public health impact: obesity, botanicals, brain-body
interactions, acupuncture, neurodegenerative diseases, and HIV/AIDS.
The next section highlights some of the advances and activities in
three of these priority areas.
ADDRESSING THE OBESITY EPIDEMIC
An alarming 65 percent of American adults,\1\ 16 percent of
adolescents, and 10 percent of American children are now overweight.\2\
Obesity results from complex interactions among human biology,
behavior, and the environment and, therefore, requires a
multidisciplinary approach to prevent and treat it. NCCAM is
contributing to the trans-NIH strategy to address this epidemic by
supporting studies of the safety and efficacy of popular, but
unsubstantiated, dietary approaches to obesity and its many
complications. One of the most popular approaches today is the diet
plan championed by the late Dr. Robert Atkins, which emphasizes a low-
carbohydrate, high-fat, high-protein regimen.
---------------------------------------------------------------------------
\1\ Journal of the American Medical Association, 288 (14): 1723-
1727, Flegal et al, ``Prevalence and trends in obesity among U.S.
adults, 1999-2000''
\2\ Journal of the American Medical Association, 288 (14): 1728-
1732, Ogden et al, ``Prevalence and trends in overweight among U.S.
children and adolescents, 1999-2000''
---------------------------------------------------------------------------
In fiscal year 2003, NCCAM-sponsored researchers reported in the
New England Journal of Medicine on a ground breaking 1-year, multi-
center trial about the effects of the Atkins diet on weight loss and
risk factors for cardiovascular disease. At 6 months, those on the low-
carbohydrate diet had lost more weight and had reduced levels of blood
lipids more than those on the conventional diet. At the end of 1 year,
however, the differences between the two groups of dieters lessened,
leading investigators to call for larger and longer-term studies. NCCAM
is working with its NIH partners to support a larger and more
definitive study.
In its intramural program, NCCAM researchers are testing whether
the dietary supplement glucosamine, used by over 4 percent of older
Americans for degenerative arthritis, causes resistance to insulin, a
condition that predisposes one to diabetes--a disease linked to
obesity. Other IRP studies are evaluating carnitine, a nutrient
essential for the normal metabolism of fats, to see whether it can
reduce abdominal fat content, stimulate weight loss, and improve
glucose utilization.
In fiscal year 2005, as part of the overall trans-NIH focus on
obesity, NCCAM will cosponsor two major initiatives in obesity
research, Neurobehavioral Basis of Obesity and Prevention and Treatment
of Pediatric Obesity in Primary Care Settings. The first seeks to
bridge the gap between understanding the molecular and genetic
regulation of food intake and behavioral influences on obesity. The
pediatric initiative will evaluate preventive and therapeutic
strategies for obesity that could be recommended for children and
adolescents in primary care settings, such as a physician's office,
primary care clinic, or HMO.
EXAMINING THE SAFETY AND EFFECTIVENESS OF BOTANICAL PRODUCTS
Approximately 14 percent of Americans use herbal supplements to
prevent disease, maintain wellness, or treat illness or pain.\3\ Many
of these people also take prescription drugs. NCCAM-supported research
is identifying herbal products that interact with drugs and the
underlying biochemical mechanisms of these interactions. For example,
studies have shown how St. John's wort and PC SPES (a botanical mixture
that had been used to treat advanced prostate cancer) induce the
activity of a key liver enzyme that is responsible for the metabolism
of some 80 percent of all drugs. This finding shows how herbal
supplements have the potential to either enhance a drug's toxicity or
reduce a drug's effectiveness when a patient takes both dietary
supplements and prescription medication.
---------------------------------------------------------------------------
\3\ Journal of the American Medical Association, 287 (3); 337-344;
Kaufman et al., ``Recent patterns of medication use in the ambulatory
adult population of the United States: the Slone survey.''
---------------------------------------------------------------------------
Each year in the United States, an estimated 70,000 people are
diagnosed with head and neck cancers, which are typically resistant to
multi-drug chemotherapy. In fiscal year 2003, NCCAM-sponsored
researchers examined extracts from the root of Scutellaria baicalensis,
a Chinese herb, for activity against head and neck cancers. The new
study is promising because it shows that the herbal extracts strongly
inhibit the growth of human head and neck cancer cells in vitro as well
as in mice with tumors composed of human cells. Future studies will
determine the herb's effects on regulating the cell replication cycle
and whether it can be translated into a safe and effective intervention
for head and neck cancer patients.
While some research studies confirmed the promise of certain
botanicals, others have found herbs that do not deliver on their
claims. One example is guggulipid, a botanical extracted from the resin
of the mukul myrrh tree, that is marketed in the United States as a
dietary supplement to help control blood cholesterol levels and
maintain a ``healthy heart.'' In an 8-week placebo-controlled study
involving over 100 subjects, NCCAM-funded scientists found that neither
the standard or even higher doses of guggulipid significantly lowered
the levels of the key low-density lipoprotein (LDL) form of cholesterol
in people with high blood cholesterol. This study highlights the need
to study popular botanicals that the public is using so that
individuals can make informed decisions regarding their own care.
In fiscal year 2005, NCCAM will co-sponsor three important
initiatives on the use of botanicals as dietary supplements. Through a
newly refined Botanical Research Centers Program being mounted with the
NIH Office of Dietary Supplements and the National Institute of
Environmental Health Sciences, NCCAM will support interdisciplinary
studies of botanicals to generate evidence regarding their safety and
potential public health benefits. NCCAM also plans to establish a Phase
I Resource Center (PRC) to define the pharmacology and optimal dosing
of botanical products and functional foods. Finally, in fiscal year
2005, NCCAM plans to initiate in vitro, animal, and preliminary
clinical studies of Silybum marianum (milk thistle) and its derivative
silymarin as a treatment for chronic hepatitis and cirrhosis of the
liver, conditions that affect millions of Americans for whom, to date,
there is no effective treatment.
Through these programs, NCCAM thoughtfully is investing in programs
of basic research to discover natural products and food supplements
that could open new avenues for prevention and treatment of conditions
that affect the health, well being, productivity, and quality of life
of millions of Americans.
INVESTIGATING BRAIN-BODY INTERACTIONS
NCCAM scientists are exploring ancient practices such as
meditation, Tai Chi, hypnosis, and yoga to understand their abilities
to harness the healing effects of the mind on the body. For example,
NCCAM grantees are conducting pilot studies of yoga as a behavioral
intervention for the management of chronic obstructive lung disease,
insomnia, and chronic low back pain, as well as investigating whether
one's spirituality and religiosity have a significant influence on
immune system functioning.
In 2003, NCCAM-funded researchers reported that a traditional
Chinese meditative exercise regimen, Tai Chi, could enhance physical
performance and immune responses in older people. As people age,
immunity to the virus that causes chicken pox wanes until the infection
can reactivate from its dormant state in nerves and develop into the
painful condition shingles. The study concluded that older adults who
participated in a form of Tai Chi for 15 weeks experienced
statistically significant increases both in ellular immune responses to
the virus and in physical performance. This is the first scientific
study to show that a CAM approach is responsible both for improvements
in physical function and in virus-specific immunity and provides the
basis for a larger study of Tai Chi currently being supported by NIH.
To further stimulate research in the field of brain-body
interactions, NCCAM is a cosponsor of several NIH research initiatives.
The first effort, entitled Mind-Body Interactions and Health:
Exploratory/Developmental Research Program, will foster program
development at institutions that have high potential for advancing
mind-body and health research. The second initiative, Research on Mind-
Body Interactions and Health, will support interdisciplinary
collaborations and innovations to understanding the underlying
processes of mind-body interactions and health and translating basic
knowledge into interventions and clinical practices.
LOOKING FORWARD
Five years ago, the discipline of rigorous CAM research was in its
infancy. Absent precedents for the field, NCCAM's initial efforts led
to supporting an array of studies spanning numerous CAM practices and
health conditions. In these first years, NCCAM found that to better
ensure that its funds yield compelling results, it needed to encourage
studies on mechanisms of action of CAM approaches, well-developed Phase
I and II clinical trials as a foundation for future definitive studies,
and collaborations between CAM and research-intensive institutions. In
the coming years, the Center will refine its research priorities even
more, to emphasize those areas and conditions for which CAM can have
the greatest health impact. To this end, in 2004, NCCAM began a formal
process to seek input from its many stakeholders, including the
scientific community, health professionals, and the public to further
target its research, training, and communication goals and to craft a
long-term plan to guide the way toward its tenth anniversary.
Complementing this strategic planning process are the trans-NIH
Roadmap for Medical Research activities in which NCCAM leadership has a
significant role. Core themes of the Roadmap resonate strongly with
NCCAM because they promise to provide NCCAM grantees access to more
sensitive technologies, richer environments for learning and conducting
interdisciplinary research, and a re-engineered platform for clinical
trials, all in ways that small institutes and centers could never
achieve on their own.
In the coming months and years, I look forward to sharing with
members of the Committee, the scientific community, practitioners, and
the public our second strategic plan and the results of the research
and training investments that we have made. Thank you for your interest
in NCCAM's progress and plans. I would be pleased to answer any of your
questions.
______
Prepared Statement of Dr. Kenneth Olden
Mr. Chairman and Members of the Committee: I am pleased to present
the President's budget for the National Institute of Environmental
Health Sciences (NIEHS). The fiscal year 2005 budget is $650,027,000,
an increase of $18,964,000 over the comparable fiscal year 2004
appropriation.
INTRODUCTION
Most complex diseases arise from the interplay between biology,
environment and behavior. It is the NIEHS' mission to understand this
interplay as it translates into increased disease risk. Thanks to the
rare confluence of technology breakthroughs in analysis of genes and
proteins and their recent application to the environmental health
sciences, gene-environment interactions can now be investigated with
more rigor and specificity. Our new opportunities within the framework
of the NIH Roadmap also offer promise for a more rapid understanding
and translation of this knowledge into improved public health. I will
outline several of the NIEHS' most important efforts.
GENES AND ENVIRONMENT
There are two principal avenues for exploration of the complex
interplay between genes and environment. One is to look at the
variations of genes themselves, and the other is to examine how genes
respond to environmental stressors. In the case of the first approach,
NIEHS is conducting the Environmental Genome Project (EGP) an effort to
resequence 544 ``environmentally responsive'' genes--genes which are
thought to be involved in an individual's susceptibility to
environmental exposures--and to identify alleles or genetic variants
associated with these genes. The key objective of the EGP is to
discover and characterize these alleles or genetic variants, called
polymorphisms, and to define their roles in the pathways by which
environmental agents exert their effects on human health and disease.
Last April, the EGP completed the first phase, publishing a catalog
of variation in over 200 genes responsible for detoxifying
environmental compounds such as pesticides, as well as metabolizing
natural biological components such as hormones. Over 17,000 single
nucleotide polymorphisms (SNPs) were identified, with more than 1,000
in coding sequences. This information is already being used to make
significant scientific discoveries. For example, it was found that
people suffering from benzene-induced leukemia lack a certain SNP in
the gene responsible for utilizing a vitamin B, folate, that healthy
people have. Thus, the ability to metabolize folate might relate to the
relative risk of developing leukemia among benzene workers.
To aid in the functional characterization of SNPs in both coding
and regulatory sequences of specific genes, NIEHS initiated the Mouse
Genetic Variation Mapping Initiative. The mouse is the most widely used
mammalian model system for the study of human health and disease for
several reasons, including the fact that the genomes of mice and other
mammals are highly conserved. Most human genes have counterparts in the
mouse genome; thus, cloning of a gene in one species often leads to
cloning of the corresponding gene in the other. The mouse also offers
well developed toxicological and pathology databases and molecular
genetic techniques for construction of gene knockout strains. Data
generated using rodent models have been used widely in preparation of
environmental regulatory policy and by the pharmaceutical industry.
One of the greatest challenges for comparative toxicogenomics is
the integration of the vast amount of genomic information being
generated for a variety of model organisms. At present, there are
several disparate but complementary databases on genomic sequences.
Most of these databases provide data on gene and genome sequences for
individual animal species. These databases do not provide a means to
link the genome data to specific environmental chemicals or to
toxicological and biological endpoints. They also do not enable
researchers to compare information about potentially similar genes and
biological responses across multiple species.
Integrating the large number of disparate data sets is the goal of
the Comparative Toxicogenomics Database (CTD). The CTD was developed
through a collaboration of five NIEHS-funded Marine and Freshwater
Biomedical Sciences Centers. The goal of the CTD is to develop a
comparative database that links sequence information for genes that are
relevant to toxicology to information about gene expression, toxicology
and biological processes. The primary focus of the CTD is on marine and
aquatic organisms as model systems for human diseases. The initial
focus is also on genes that have been identified through the NIEHS' EGP
as important for toxicology in these model systems. However, the
database will eventually merge all gene sequence information generated
on all vertebrates and invertebrates, including aquatic organisms,
worms, flies, rodents, and people. The CTD provides information about
gene curation and annotation (gene synonyms, sets and functions) and
links between gene sequence and toxicity data published in the
scientific literature. These aspects of the database represent an
important advancement for comparative toxicogenomics. Understanding
these mechanisms will allow more informed assessment of human risk by
extrapolating toxicity data from animal models to people and will
provide a mechanism by which members of the research community can
share their data and promote fruitful avenues for future toxicological
research.
At present, the CTD is the only fully curated, publicly available
database of its kind in the world. However, it serves as a prototype
database and data resource for more comprehensive efforts ongoing at
the NIEHS. The centerpiece for these discoveries is the NIEHS' National
Center for Toxicogenomics (NCT), which uses a multidisciplinary
approach to identify genes and proteins affected by specific
environmental exposures. When a person is exposed to a chemical,
physical, or biological agent, cells in the body may respond by
switching on some genes and switching off others, potentially changing
the proteins that are produced by the cells. The on/off pattern of
various genes is different for each specific exposure, creating a
characteristic pattern or ``signature,'' which scientists hope will be
useful in classifying chemicals by their effects on various cellular
processes. By constructing and populating a database of chemical
effects on biological systems, the NCT is assisting the field of
environmental health research to evolve into an information science in
which gene and protein expression datasets are compiled and made
readily available to the scientific community. By building on the data
infrastructure being developed through the CTD and other databases,
NIEHS scientists are developing the sequence-driven and context-
documents Chemical Effects in Biological Systems (CEBS) knowledge base.
CEBS is planned as a public toxicogenomics knowledge base that combines
and integrates scientific data from a multitude of public domain data
sources. These data sources include studies of genetic polymorphisms,
gene expression and proteomics, metabolism and toxicology. Once
sufficient high quality data have been accumulated and assimilated, it
will become possible to characterize an unknown environmental exposure
by comparing its gene and/or protein expression profile to compendia of
expression profiles in the database. Ultimately, the NCT will develop
the capacity to use gene expression signatures and other data to
facilitate characterization of toxicants and their biological effects.
Through the predictive capabilities expected from toxicogenomics,
adverse toxicity in clinical trials will be reduced and the efficiency
of bringing new therapeutics to the public will be increased; adverse
effects from long-term use or from combinations of therapeutic agents
will be better understood and reduced. The final payoff for investing
in CTD and CEBS will be more rational environmental health policy and
an improved understanding of gene-environment contributions to the
major causes of human death and disease.
OBESITY AND ENVIRONMENT
Environment and behavior intersect in fundamental ways,
intersecting with our biology but also with each other. In no area of
public health is this more apparent than with the problem of obesity.
There is a growing body of literature that illustrates the negative
physical and mental health effects of unregulated and poor urban,
rural, and suburban development and planning. These studies have
documented increased rates of obesity, diabetes, depression, anxiety,
and heart disease in these poorly developed areas. For example, in
sprawling communities, higher dependence on motor vehicles has resulted
in polluting the atmosphere with ground-level ozone and particulate
matter, contributing to human health problems such as lung and
cardiovascular disease. People most affected by air pollution include
older adults with pre-existing diseases; children, especially those
with asthma; persons with inadequate health care; and even healthy
individuals who work and exercise outdoors. Lack of safe sidewalks in
growing urban areas has resulted in a reduction in the number of
children walking or biking to schools. Today, only 10 percent of
children walk or bicycle to school--a 40 percent reduction over the
last 20 years (according to researchers in Urban Land). Research
suggests that inadequate urban planning, such as a lack of bike paths
and sidewalks, results in a more sedentary lifestyle of children,
which, in turn, may be a factor in the growing rates of childhood
obesity. All of these examples demonstrate how the physical or built
environment influences choices that ultimately affect health.
The NIEHS is designing a program as part of the trans-NIH obesity
initiative which is designed to examine how the built environment
affects obesity and the effectiveness of changes in community planning,
design, and development in reducing the extent of obesity and
associated comorbidities. These intervention research projects will
develop tools to characterize and measure individual and population-
level indicators of healthful communities--and of residents' lifestyles
and behaviors--that prevent or reduce obesity. We hope that not only
will studies of interaction between parameters of the built environment
and individual lifestyle choices and behaviors help delineate factors
that can prevent or reduce obesity, but also that this work will point
the way towards new, cost-effective intervention strategies that
promote healthful environments and behaviors.
In a related initiative, NIEHS is partnering with the Robert Wood
Johnson Foundation to support a program called Active Living by Design,
which will provide support to 25 communities across the country to
implement active living programs, policies, and communication
strategies to improve community development and promote more healthy
lifestyles. The NIEHS is providing an evaluation component to the
program to determine the efficacy of various policies and promotions in
reducing obesity.
It is critical to delineate the role and impact of community
design, planning, and development on individual and population health
by understanding the contribution of urban/rural planning (i.e., land
use decisions), housing structure, transportation issues, and the
availability of public and green spaces as determinants of mental
health, physical activity, nutrition, and access to healthy foods. In
turn, modifying such parameters may reduce the prevalence of obesity in
adults and children. This research effort will require integrated,
interdisciplinary research teams, including biomedical scientists,
behavioral scientists, social scientists, clinicians, epidemiologists,
urban planners, developers, and architects, as well as active
participation of community members. It is expected that such research
will result in a greater understanding of the health benefits of living
in communities that promote healthful environments and behaviors and
may also impact policy for land use and public health.
TOXICOLOGICAL EVALUATION OF NANOSCALE MATERIALS
Nanoscale materials are a broadly defined set of substances where
at least one critical dimension is less than 100 nm. Ultrafine
particulate matter, e.g. the very smallest particles of soot from such
sources as diesel exhaust, is a well-known example of ambient
nanoparticles; however, this initiative will initially focus on
manufactured nanomaterials of current or projected commercial
importance. Nanoscale materials can in theory be engineered from nearly
any chemical substance; semiconductor nanocrystals, organic dendrimers,
and carbon fullerenes and carbon nanotubes are a few of the many
examples. Nanoscale materials are already appearing in commerce as
industrial and consumer products and as novel drug delivery
formulations. Commercial applications and resultant opportunities for
human exposure may differ substantially for nanoscale vs. ``bulk''
materials.
Currently there is very little research focus on the toxicology of
manufactured nanomaterials. Studies from the ultrafine particle
inhalation toxicology literature hint at the complexity of the topic
and suggest that nanoparticle size can impact toxicity equally if not
more so than chemical composition. There are indications in the
literature that manufactured nanomaterials may distribute in the body
in unpredictable ways and that certain nanoparticles have been observed
to preferentially accumulate in particular organelles. Surface
properties can be changed by coating nanoparticles with different
materials, but surface chemistry also is influenced by the size of the
particle. This interaction of surface area and particle composition in
eliciting biological responses adds an extra dimension of complexity in
evaluating potential adverse events that may result from exposure to
these materials.
The National Toxicology Program (NTP) is developing a broad-based
research program to address potential human health hazards associated
with the manufacture and use of nanoscale materials. The intent of the
NTP/NIEHS research program is to evaluate the toxicological properties
of major nanomaterials classes which represent a cross-section of
composition, size, surface coatings, and physico-chemical properties,
and use these as model systems to investigate fundamental questions
concerning if and how nanomaterials can interact with biological
systems. Some of these fundamental questions include: What are the
appropriate methods for detection and quantification of nanoscale
particles in tissues? How are nanoparticles absorbed, distributed in
the body and taken up by cells? Are there novel toxicological
interactions?
Discussion and review of efforts in this area has highlighted the
need for studies of nanoscale materials that not only apply existing
toxicology testing methodologies, but also explore the development of
appropriate novel toxicological methods to adequately assess potential
human health effects. The NIEHS is looking ahead to be able to
supplement our critically inadequate knowledge of this rapidly emerging
technology.
______
Prepared Statement of Dr. Thomas R. Insel
Mr. Chairman, and members of the Committee, I am pleased to present
the President's budget request for the National Institute of Mental
Health (NIMH) for fiscal year 2005, a sum of $1,421 million, which
reflects an increase of $39 million over the comparable fiscal year
2004 appropriation.
In my statement, I will call to your attention the immense burden
on our Nation of mental and behavioral disorders. In addition, in the
context of a brief review of our research activities and
accomplishments, I will describe some of our efforts, in collaboration
with trans-NIH initiatives, to bring new treatments from the laboratory
to the clinical research arena and ultimately to widespread practice in
the community.
BURDEN OF MENTAL ILLNESS
The National Institute of Mental Health faces an enormous
challenge: to reduce the burden of mental and behavioral disorders
through research on mind, brain, and behavior. Mental disorders are
real illnesses that can be diagnosed and in many cases, treated
effectively. The need is vast: 450 million people worldwide suffer from
a mental disorder. Mental illnesses account for four of the top six
causes of disability among 15-44 year olds in the Western world. By
2020, psychiatric and neurological conditions will have likely
increased their share of the total global burden by almost half, from
10.5 percent to 15 percent.
In addition to morbidity, mental illnesses are a substantial source
of mortality. Of the 30,000 Americans who die by suicide each year, 90
percent have a mental illness. Deaths from suicide outnumber deaths
from homicide (18,000) as well as deaths from AIDS and most forms of
cancer. Suicide is high among several ethnic minority groups, though
remains highest in older white males. Between 1952 and 1992, the
incidence of suicide among adolescents and young adults nearly tripled;
currently it is the third leading cause of death in adolescents.
In addition to the emotional costs, the economic costs of mental
illness are staggering. According to the recent report from the
President's New Freedom Commission on Mental Health, the cost in the
United States from both direct (treatment-related) and indirect
(productivity loss) expenses may exceed $150 billion per year with
rapid annual increases, especially in the drug treatment area. Adding
to that, more than three million people are receiving disability
benefits due to mental disorders. They constitute nearly 28 percent of
disabled workers in the Social Security Disability Insurance Program,
and more than 35 percent of people with disabilities receiving
Supplemental Security Income. Together they accounted for an estimated
$25 billion dollars in cash benefits in 2001.
SCIENCE TO SERVICE
For many mental disorders, there is some form of treatment, but
there is no cure. The report from the President's New Freedom
Commission on Mental Health describes the need for transforming the
delivery of evidence-based treatment and services to communities where
they can directly benefit people with mental illness. To achieve this
goal, NIMH recognizes the need for the research enterprise to partner
with other organizations such as the Substance Abuse and Mental Health
Services Administration (SAMHSA), state governments, and advocacy
groups. In one such example, NIMH and SAMHSA recently funded nine one-
year grants to state mental health agencies to support planning
activities toward the implementation of evidence-based practices.
Proposed science to service research activities include devising
evidence-based group-focused activities for specific ages (child,
adult); managing medication for those with schizophrenia; and providing
cognitive behavioral therapy for people with depression. Each grant is
expected to result in future research and service development
initiatives. Translating scientific breakthroughs into far-ranging
clinical care, we believe, is an urgent and achievable task.
PROGRESS IN GENETICS
In addition to applying what we already know, we must continue the
scientific efforts required to develop better treatments to bring us
closer to our ultimate goals of curing or preventing severe mental
health disorders. To attain these ambitious goals, we will need a much
larger variety of medications and behavioral therapies than are
currently available--treatments that can be tailored to work for all
those who need them, not just a small subset. As an initial first step,
we must discover how genes and the environment interact to produce the
biological variations that can signal vulnerability to disease. This
year has been remarkable in its wealth of discoveries of genes as well
as gene-environment interactions. In depression, for example, NIH-
sponsored researchers found that a variation in the gene that regulates
serotonin transmission can make a person more vulnerable to depression
when faced with stressful life experiences. Those without the gene
variation had no such vulnerability, and appeared to be resilient even
in the face of many life stresses. Those with the gene variation were
not depressed until and unless they faced major life stressors. This
suggests that some of the environmental contributors to illness may
only be detected by first identifying variations in genetic risk.
Future research could help us apply this information to identify those
most at risk, and develop treatments that either target genes or the
environment, or both. It also suggests a new model with which to test
genetic vulnerability and environmental stresses in other major
diseases, such as schizophrenia, anxiety disorders, or eating
disorders.
This year we have also seen exceptional progress in research on
schizophrenia. Several genes have been found which appear to
significantly contribute to the development of schizophrenia, providing
at least a partial blueprint for the genetic risk architecture of the
disease. While we still need to learn more about how they work, this
group of genes should bring us closer to diagnostic tests for early
detection, new targets for treatment, and even new strategies for
prevention. In other studies, genes have been found which are thought
to play a role in obsessive-compulsive disorder, panic disorder, and
autism. NIMH researchers have also identified genes involved in memory
and information processing, both of which are impaired in schizophrenia
and various other disorders. These studies were among those named
collectively as the number two scientific ``breakthrough of the year''
by the prestigious journal Science in December. Most of the studies
listed were conducted by intramural or NIMH-funded investigators.
Studies this year have also provided new insight into the neural
circuitry of anxiety and fear processing, suggesting new targets for
drug development to treat anxiety, post-traumatic stress disorder, and
various phobia disorders.
SCHIZOPHRENIA TREATMENT INITIATIVE
While the news on schizophrenia has been exciting, we recognize
that the road from gene discovery to prevention and treatment is
neither simple nor rapid. To accelerate this process, we created a new
initiative on schizophrenia research. A primary component is a new
intramural interdisciplinary team, ranging from molecular to clinical
scientists, who will lead a broad effort to understand how different
gene variations alter neural networks and disrupt brain activity,
leading to cognitive impairment and psychosis. The team will work to
identify the role of these vulnerability genes, including their
individual contributions to risk, severity of the disease, and drug
response.
A second component of the initiative is a program that targets
cognitive problems for people with schizophrenia. Cognitive deficits,
such as trouble with memory, attention, and executive function
(capacity to make judgments and control impulses) are major
determinants and predictors of long-term disability in schizophrenia.
They remain a significant barrier to a productive life for people with
the disease, yet the medications currently available provide no relief
for cognitive problems. There has been a lack of scientific consensus
on which cognitive impairments should be targeted and which tools are
best for measuring them. As a result, the FDA has not been able to
recognize cognition in schizophrenia as a valid treatment endpoint for
drug registration. To address these issues, NIMH launched the
Measurement and Treatment Research to Improve Cognition in
Schizophrenia (MATRICS) program. It brings together representatives
from academia, industry, and regulatory agencies to develop a
comprehensive assessment tool to measure cognitive functioning in
people with schizophrenia. The second phase is to develop and test
novel compounds designed to enhance cognition.
ROADMAP
For most of our recent genetic discoveries, we lack the molecular
tools needed to link the genes to new treatments. The search for new
molecular tools for schizophrenia and other mental disorders will be
aided greatly by one of the NIH Roadmap initiatives that will establish
a repository of diverse organic chemicals. Organic chemicals, commonly
referred to as ``small molecules,'' have proven to be extremely
important to researchers exploring the functions of the cell at the
molecular level. In fact, most medicines, from aspirin to
antihistamines, are small molecule compounds. This new ``molecular
library'' will offer researchers access to hundreds of thousands of
small organic molecules that can be used as chemical probes to study
cellular pathways. These compounds will help validate new targets for
drug therapy more rapidly, and will enable other researchers to move
them into the drug-development pipeline.
AUTISM
NIMH plays a major role in a broad-based NIH effort to create a
network of autism research centers focusing on the biomedical and
behavioral aspects of the disease. Five institutes at NIH are
coordinating their research efforts in an initiative called the Studies
to Advance Autism Research and Treatment (STAART) Centers program. This
year, the institutes awarded grants to support six new autism research
centers, in addition to the two that were funded last year. NIH expects
to spend $65 million over five years for the eight centers.
NIMH is the lead agency for the Interagency Autism Coordinating
Committee (IACC), a group charged with coordinating research and other
efforts on autism within the Department of Health and Human Services
(HHS). NIMH took the lead in organizing the ``Autism Summit Conference:
Developing a National Agenda,'' a joint effort of the HHS and the
Department of Education, held in November 2003. About 650 people
attended the meeting to address three major areas of emphasis:
biomedical research, implementing early screening and diagnosis, and
improving the accessibility and coordination of services. A key focus
of the meeting was the introduction of a 10-year national research
agenda, developed by an IACC-appointed expert panel. The research
agenda identified roadblocks hindering progress in understanding
autism's causes and developing treatment, and provided goals and
strategies for the next 10 years to overcome these challenges. These
research efforts will be carried out through the centers of excellence
within the STAART network.
PRACTICAL CLINICAL TRIALS
To improve human health, scientific discoveries must be translated
into practical applications. Such discoveries typically begin at ``the
bench'' with basic research where scientists study the mechanisms and
pathogenesis of a disease at a molecular or cellular level--then
progress to the clinical level, or the patient's ``bedside.'' Equally
important is the translation from bedside to practice. Moving new drugs
and therapies more quickly and smoothly out of the research environment
and into the hands of clinicians is a key feature of the NIH Roadmap.
To achieve this, NIH will promote the creation of better integrated
networks of academic centers that work jointly on clinical trials and
which include community-based physicians who care for large groups of
patients. Implementing this vision will require new ways of organizing
the methods in which clinical research information is recorded,
defining new standards for clinical research protocols, and creating
new models of cooperation between NIH and patient advocacy alliances.
For its part, NIMH is finishing up four large-scale, longitudinal
research studies to compare therapeutic approaches for serious mental
illnesses, including schizophrenia, Alzheimer's disease, major
depression, and bipolar disorder. These are different than most
clinical trials, which are usually of short duration and limited to
assessment of clinical symptoms. The NIMH studies are testing the
various treatment options currently available for these disorders in
diverse community populations, recruiting people from a variety of
``real world'' practice settings, and expanding outcome measures to
include functional status and economic costs. The clinical populations
currently enrolled in these NIMH treatment trials are among the largest
and best characterized populations with bipolar disorder,
schizophrenia, and depression ever studied through clinical trials in
mental health. These trials will answer urgent questions about the
treatment of adolescents with depression, the use of atypical anti-
psychotics in people with schizophrenia and Alzheimer's, and the
optimal long-term medication for bipolar patients. When the studies are
over within the next two years, we hope to be able to continue
utilizing this valuable clinical infrastructure--made up of staff,
investigators, federal and state agencies, industry, patients, and
patient advocacy groups--to answer other critical public health
questions in diverse populations.
PRIORITY-SETTING
Over the past five years, we have witnessed unparalleled advances
in the basic sciences relevant to mental health. Genomics, imaging, and
many areas of neurobiology are beginning to reveal a new understanding
of normal and abnormal behavior. Against this backdrop of scientific
progress, we continue to face extraordinary challenges for our patients
with mental disorders. Science now yields opportunities that promise to
deliver for each of these challenges. To realize this promise, we must
define areas of high priority. To assist us, workgroups of our National
Advisory Mental Health Council are reviewing the NIMH portfolio
initially in two key research areas: clinical trials and basic science.
Both workgroups plan to deliver reports by May 2004 and both will
define priority areas using the criteria of relevance, traction, and
innovation. Both workgroups have done an impressive job in reviewing
the hundreds of relevant grants in the portfolio. We look forward to
their recommendations, as well as to those of our Outreach Partners in
every state, the mental health advocacy community, and the public. We
rely on these groups to help us meet our ultimate goal of relieving the
profound misery suffered daily by patients and families affected by
mental disorders.
______
Prepared Statement of Dr. Raynard Kington
Mr. Chairman, members of the Committee: I am pleased to present the
President's budget request for the Office of the Director (OD) for
fiscal year 2005, a sum of $359,645,000, which reflects an increase of
$32,556,000 over the comparable fiscal year 2004 appropriation. The OD
provides leadership, coordination, and guidance in the formulation of
policy and procedures related to biomedical research and research
training programs. The OD also is responsible for a number of special
programs and for management of centralized support services to the
operations of the entire NIH.
The OD guides and supports research by setting priorities;
allocating funding among these priorities; developing policies based on
scientific opportunities and ethical and legal considerations;
maintaining peer review processes; providing oversight of grant and
contract award functions and of intramural research; communicating
health information to the public; facilitating the transfer of
technology to the private sector; and providing fundamental management
and administrative services such as budget and financial accounting,
and personnel, property, and procurement management, administration of
equal employment practices, and plant management services, including
environmental and public safety regulations of facilities. The
principal OD offices providing these activities include the Office of
Extramural Research (OER), the Office of Intramural Research (OIR), and
the Offices of: Science Policy; Communications and Public Liaison;
Legislative Policy and Analysis; Equal Opportunity; Budget; and
Management. This request contains funds to support the functions of
these offices.
In addition, the OD also maintains several trans-NIH offices and
programs to foster and encourage research on specific, important health
needs; I will now discuss the budget request for the OD in greater
detail.
NIH ROADMAP
As part of the NIH Roadmap for Medical Research, the NIH has
launched initiatives in fiscal year 2004 critical to addressing the
roadblocks to the acceleration of science conduct and transfer to the
public. These initiatives promise to yield far-reaching dividends in
medical knowledge and improved health for the public. Under the theme
of New Pathways to Discovery, initiatives are aimed at quantifying and
cataloging complex biological systems and in developing a better ``tool
box'' for today's researchers, for research teams of the future, and
for re-engineering the clinical research enterprise. Examples of
initiatives include the creation of an accessible public library
database for chemically diverse small molecules, centers that will
create new tools to describe the dynamics of protein interactions,
development of novel technologies to study cellular metabolites,
creation of national software engineering system that can facilitate
the ability of scientists to tap into supercomputing networks and share
and analyze complex data, and the early conceptual development of
nanomedicine. The NIH Roadmap initiatives also have taken steps to
prepare Research Teams of the Future, the second theme, by encouraging
scientists and research institutions, including the NIH, to test
alternative models for conducting research that take advantage of the
scientific advances and complexities. A major focus has been placed on
planning and research workforce training for the conduct of
interdisciplinary research, that research that spawns new disciplines
of science. In addition, a new award--the NIH Director's Pioneer
Award--will support a select group of investigators who have the
potential for ground-breading discoveries. Ultimately findings from the
laboratory must reach the public, and the initiatives under the third
them--Re-engineering the Clinical Research Enterprise--are geared to
address the roadblocks to the conduct of clinical research and its
translation to patients. These initiatives include the exploration of
the ability to create and enhance interoperability among clinical trial
networks, the testing the feasibility of establishing a National
Clinical Research Associations program where community-based clinicians
are trained to participate in studies and play a role in augmenting the
transfer of research to their patients, and the assessment of patient-
reported chronic disease outcomes. Critical work continues in the area
of research policy analysis and coordination with an emphasis on
harmonization and standardization of policies and requirements
pertaining to clinical research. In addition, extension and expansions
of clinical research training programs extramurally and intramurally
have been initiated.
THE OFFICE OF AIDS RESEARCH
The Office of AIDS Research (OAR) coordinates the scientific,
budgetary, legislative, and policy elements of the NIH AIDS research
program. Our response to the epidemic requires a unique and complex
multi-institute, multi-disciplinary, global research program. Perhaps
no other disease so thoroughly transcends every area of clinical
medicine and basic scientific investigation, crossing the boundaries of
the NIH Institutes and Centers. This diverse research portfolio demands
an unprecedented level of scientific coordination and management of
research funds to identify the highest priority areas of scientific
opportunity, enhance collaboration, minimize duplication, and ensure
that precious research dollars are invested effectively and
efficiently, allowing NIH to pursue a united research front against the
global AIDS epidemic. Each year, OAR oversees the development of the
comprehensive NIH AIDS-related research plan and budget, based on
scientific consensus about the most compelling scientific priorities
and opportunities that will lead to better therapies and prevention
strategies for HIV disease. The Plan serves as the framework for
developing the annual AIDS research budget for each Institute and
Center; for determining the use of AIDS-designated dollars; and for
tracking and monitoring those expenditures. OAR identifies scientific
areas that require focused attention and facilitates multi-institute
activities to address those needs. OAR coordinates, monitors and
fosters plans for NIH involvement in international AIDS research and
training activities. OAR supports a number of initiatives to enhance
dissemination of research findings to researchers, physicians, patients
and communities. The fiscal year 2005 budget request for OAR is
$61,435,000.
THE OFFICE OF RESEARCH ON WOMEN'S HEALTH
The Office of Research on Women's Health (ORWH), the focal point
for women's health research for the Office of the Director,
strengthens, enhances and supports research related to diseases,
disorders, and conditions that affect women, and sex/gender studies on
differences/similarities between men and women; ensures that women are
appropriately represented in biomedical and biobehavioral research
studies supported by the NIH; and, develops opportunities for the
advancement of women in biomedical careers and investigators in women's
health research. The report, An Agenda for Research on Women's Health
for the 21st Century, provides a framework for the ORWH to collaborate
with the scientific and advocacy communities to address gaps in
knowledge about women's health and sex and gender factors in health and
disease. The fiscal year 2005 budget request of $41,577,000 includes an
increase of $626,000 over the fiscal year 2004 appropriation.
Research priorities for women's health emphasize the importance of
interdisciplinary research with collaboration and integration of
knowledge from multiple areas of scientific expertise; lifespan issues
and the continuum from intrauterine life into elderly years; health
disparities/differences and diversity among different populations or
subpopulations of women; and, sex/gender differences in health and
disease and therapeutic interventions at genetic, molecular, cellular,
and functional levels. Areas of research interest for 2005 include:
pathogenesis of diseases including prevalence/validation of sex
differences in diagnosis/treatment of disorders/diseases; clinical
trial methodology; mental health studies; new agents for management of
menopausal symptoms; treatments/interventions for diseases that show
enhanced clinical features in women; and other specific areas such as
CFS, and benign gynecologic disorders including uterine fibroids.
Special emphasis areas for women's health research include genetics/
pharmacogenomics, and the genetic, molecular and cellular bases for
action of pharmacologic agents known to have differential effects in
females; and, prevention and treatment, from basic biological factors
to effects of risk behaviors or interventions. There is expansion of
new research in the ORWH specialized centers of interdisciplinary
research in women's health and sex and gender factors, and the unique
ORWH interdisciplinary career development program in women's health
research that fosters the mentored development of junior faculty and
assists them in bridging advanced training towards a goal of research
independence. In addition, the ORWH has now implemented a new
Intramural Program on Research on Women's Health to focus on NIH
intramural women's health and sex and gender comparison research. The
ORWH continues to partner with Institutes and Centers to ensure
compliance with NIH policies for the inclusion of women and minorities
in clinical research, and that analyses by sex/gender are addressed by
investigators funded by the NIH.
THE OFFICE OF BEHAVIORAL AND SOCIAL SCIENCES RESEARCH
The NIH has a long history of funding health-related behavioral and
social sciences research, and the results of this work have contributed
significantly to our understanding, treatment, and prevention of
disease. The Office of Behavioral and Social Sciences Research (OBSSR)
furthers NIH's ability to capitalize on the scientific opportunities
that exist in behavioral and social sciences research by providing
leadership in identifying and implementing research programs in
behavioral and social sciences that are likely to improve our
understanding of the processes underlying health and disease and
provide directions for intervention. OBSSR works to integrate a
behavioral and social science approach across the programs of the NIH.
The fiscal year 2005 OD budget includes $26,321,000 for OBSSR, an
increase of $415,000 over the fiscal year 2004 appropriation.
Many exciting scientific developments are occurring at the
intersection of behavioral and social science research and biomedical
research. It has become apparent that increasingly, scientific advances
are being made at the interfaces of traditional disciplines, and that
approaches to science are becoming more integrative. OBSSR has begun
development of a program to provide interdisciplinary training to
postdoctoral fellows in NIH intramural laboratories. This program would
provide a mechanism hereby an individual with a PhD in a behavioral or
social science discipline might acquire interdisciplinary training that
included biomedical research. Alternatively, someone trained in a more
traditional biomedical field would receive postdoctoral training that
included a behavioral or social science component. In addition to the
benefits to be realized by the individual trainees, this program would
also show NIH leading, by example, our Roadmap efforts to build
interdisciplinary Research Teams of the Future.
OBSSR is also developing an initiative to advance discovery of
scientific knowledge about eHealth technologies for health behavior
change and chronic disease management. Consumers, patients, and
providers are increasingly using eHealth applications, particularly the
Internet, to seek health information for themselves or family and
friends, communicate with others who have a similar disease or illness,
and to communicate with their health care providers. These technologies
offer people the ability to obtain health information at relatively low
cost, including those with limited or no access to health care
professionals or services, and historically underserved populations.
While the use of eHealth interventions is becoming widespread, these
techniques have yet to receive much rigorous evaluation. This
initiative's goal is to bring together components of NIH, the Robert
Wood Johnson Foundation and other public agencies and private
foundations in a ``meeting of the minds'' about the state of eHealth
evaluation research for health behavior change and chronic disease
management, future directions in the field, and the role of NIH and
others in developing a research agenda for this area.
Behavioral and social factors contribute significantly to racial
and ethnic health disparities. Consequently, OBSSR is committed to
developing better knowledge of specific pathways to health disparities
and to finding solutions. In February 2003, OBSSR published in the
American Journal of Public Health a set of papers presenting scientific
evidence of the effects of racial/ethnic bias on health and identifying
areas for future research to further explicate the relationship. The
papers were the product of an OBSSR meeting of approximately 100
leading scientists held in April 2002. Currently, OBSSR is convening
discussions among ICs regarding the role of social and behavioral
science in their health disparities research activities and avenues for
coordinated initiatives.
An effective way to ensure that results of behavioral and social
science improve our society's health involves incorporating these in
clinical practice. In order to start this process at an early stage in
the training of the next generation of physicians, OBSSR funded the IOM
to determine how to improve medical education. The results of this
study [April 2004] will inform a training initiative that OBSSR with
several ICs will launch this year.
THE OFFICE OF DISEASE PREVENTION
The primary mission of the Office of Disease Prevention (ODP) is to
stimulate disease prevention research across the NIH and to coordinate
and collaborate on related activities with other federal agencies as
well as the private sector. There are several other offices within the
ODP organizational structure.
The Office of Medical Applications of Research (OMAR) has as its
mission to work with NIH Institutes, Centers, and Offices to assess,
translate and disseminate the results of biomedical research that can
be used in the delivery of important health services to the public. The
Office of Disease Prevention (ODP) has several specific programs/
offices that strive to place new emphasis on the prevention and
treatment of disease.
In fiscal year 2005, the Office of Dietary Supplements (ODS) within
ODP requests a budget of $26,218,000, an increase of $414,000 over the
fiscal year 2004 appropriation. In fiscal year 2004, ODS published its
5-year Strategic Plan for 2004-2009, a major component of which is to
significantly expand efforts to address the role of dietary supplements
in reducing the risk for chronic diseases. It will continue to promote
the scientific study of the use of dietary supplements by supporting
investigator-initiated research in conjunction with other ICs at NIH
and stimulating research through conduct of conferences and through
presentations at national and international meetings.
ODS, in collaboration with the National Heart, Lung, and Blood
Institute and other NIH ICs, has sponsored a systematic review of the
relationship between omega-3 fatty acids and a series of clinical
indications, particularly coronary heart disease. Several reports will
be published in fiscal year 2004 based upon this review, which will
serve as the basis for planning further NIH research on omega-3 fatty
acids. Congressional language in recent appropriation reports directed
ODS to enhance an ongoing collaboration for the development,
validation, and dissemination of analytical methods and reference
materials for botanical dietary supplements. ODS works with other
partners in the public and private sectors to meet this objective. ODS
supports the National Health and Nutrition Examination Survey (NHANES),
conducted by the National Center for Health Statistics at the Centers
for Disease Control and Prevention, in order to provide more
information about dietary supplement use in the U.S. population.
This will inform future research about potentially important target
populations, such as children, women, and the elderly. Funding is used
to create and populate a database of dietary supplements, as well as to
support the measurement of blood levels of key metabolites associated
with dietary supplement use. ODS collaborates with USDA to develop an
analytically-based database of dietary supplement ingredients. ODS
collaborates with other federal agencies to develop an approach to
assessment of the health effects of bioactive factors in foods and
dietary supplements. In its continuing efforts to inform the public
about the benefits and risks of dietary supplements, ODS collaborates
with USDA on the International Bibliographic Information on Dietary
Supplements (IBIDS) database, which now includes a consumer-oriented
search strategy. It has also disseminated a database devoted to federal
funding of dietary supplement research, called CARDS, which is
currently populated with data about the NIH investment from fiscal year
1999-2002. ODS publishes Fact Sheets about vitamin and mineral dietary
supplements in collaboration with the NIH Clinical Center, as well as
Fact Sheets about botanical supplements.
Another component of ODP, the Office of Rare Diseases (ORD) was
formally established through the Rare Diseases Act of 2002, Public Law
107-280. The purpose of this Act is to increase the national investment
in the development of diagnostics and treatments for approximately 25
million patients with more than 6,000 rare diseases. A rare disease is
defined as one where fewer than 200,000 persons are affected in the
United States. The fiscal year 2005 budget request for ORD is
$15,787,600, an increase of $253,000 above the fiscal year 2004
appropriation.
Through its Extramural Research Program, the ORD supports a Rare
Diseases Clinical Research Network with NIH Institutes and Centers
(ICs). The major goals for the network include the systematic
collection of clinical information to develop biomarkers and new
approaches to diagnosis, treatment, and prevention of rare diseases,
and to promote training of new clinical research investigators in rare
diseases. ORD funded seven Rare Diseases Clinical Research Consortia
and one Data and Technology Resources Coordinating Center. The
consortia focus on urea cycle disorders, inborn errors of metabolism,
rare neurological channelopathies, idiopathic bone marrow failure
states and cytopenias, vasculitides, and defects in steroidogenesis.
The patient support organizations are closely integrated into the
consortia and the network.
The ORD Intramural Research Program promotes training in the areas
of clinical and basic research into rare diseases and in biochemical
genetics, fosters protocol-based initiatives into rare diseases not
currently investigated in the intramural program, assists in the
investigation of select, unique disorders of unknown etiology, provides
overall research support for diagnostics and therapeutics of rare
disorders, and supports five Bench-to-Bedside grants.
In its Scientific Conferences Program, in fiscal year 2004, the ORD
will cosponsor more than 70 scientific conferences on rare diseases.
The 460 conferences sponsored to date since 1995 have been shown to be
excellent venues to establish a research agenda for specific rare
diseases, take advantage of scientific opportunities, or eliminate
barriers to dvancing research.
To provide more comprehensive information, ORD, together with the
National Human Genome Research Institute (NHGRI), established the
Genetic and Rare Diseases Information Center to respond to requests for
information about genetic and/or rare disorders. In its third year of
operation, the information center broadened its language base to
include Spanish in addition to English.
In fiscal year 2004, ORD plans to establish a Trans-NIH Rare
Diseases Working Group to encourage collaborative research activities,
provide opportunities for input as new rare diseases research programs
unfold, and gather information about the rare disease research programs
supported by the ICs and Offices for mandated annual and biennial
reports.
THE OFFICE OF SCIENCE EDUCATION
The Office of Science Education (OSE) plans, develops, and
coordinates science education programs to strengthen and enhance
efforts of the NIH to attract young people to biomedical and behavioral
science careers and to improve science literacy in both adults and
children. The office's mission is to help people understand and use new
knowledge uncovered by the NIH in pursuit of better health for
everyone. The OSE works toward this mission by: creating programs to
improve science education in schools (the NIH Curriculum Supplement
Series); creating programs that stimulate interest in health and
medical science careers (the new LifeWorks Web site); creating programs
to advance public understanding of medical science, research, and
careers; promoting NIH educational resources and programs; and advising
NIH leadership about science education issues. All office programs
target diverse populations including under-served communities, women,
and minorities, with a special emphasis on the teachers of students
from Kindergarten through grade 12. The OSE works closely with NIH
institutes, centers, and offices on science education issues, and
maintains the OSE Web site as a source of information about available
resources and programs. http://science.education.nih.gov.
The NIH Curriculum Supplements series are National Science
Education Standards-based lesson plans that are distributed free to K-
12 teachers across the country. They incorporate the best of both
science and education communities, and are intended to update science
content and allow the teacher to incorporate the latest NIH research
into classroom instructions. Life Works is a new OSE Web site created
as a source of career information for students, teachers, counselors,
and parents. The site will allow exploration of the educational
requirements, knowledge, skills, and abilities required for over 100
health and medical science careers. The fiscal year 2005 Budget request
for OSE is $3,899,000.
LOAN REPAYMENT AND SCHOLARSHIP PROGRAM
The NIH, through the Office of Loan Repayment and Scholarship
(OLRS), administers the Loan Repayment and Undergraduate Scholarship
Programs. The NIH Loan Repayment Programs (LRPs) seek to recruit and
retain highly qualified physicians, dentists, and other health
professionals with doctoral-level degrees to biomedical and behavioral
research careers by countering the growing economic disincentives to
embark on such careers, using as an incentive the repayment of
educational loans. There are loan repayment programs designed to
attract individuals to clinical research, pediatric research, health
disparities research, and contraception and infertility research, and
to attract individuals from disadvantaged backgrounds into clinical
research. The AIDS, Clinical, and General Research Loan Repayment
Programs are designed to attract investigators and physicians to the
NIH's intramural research and research training programs. The NIH
Undergraduate Scholarship Program (UGSP) is a scholarship program
designed to support the training of undergraduate students from
disadvantaged backgrounds in biomedical research careers and employment
at the NIH. The fiscal year 2005 Budget request for OLRS is $7,250,000.
Thank you for giving me the opportunity to present this statement;
I will be pleased to answer questions.
______
Prepared Statement of Dr. Patricia A. Grady
Mr. Chairman and Members of the Committee: The fiscal year 2005
budget includes $139.198 million, an increase of $4.497 million over
the comparable fiscal year 2004 appropriation level.
I am pleased to be here today to discuss the activities of the
National Institute of Nursing Research (NINR). NINR supports research
that converges well with NIH's top priorities and activities. Our
research emphases are also reflected in the NIH Roadmap, the strategy
to accelerate scientific discoveries and take new approaches to make
them more rapidly available to patients. NINR's scientific community is
excited about the opportunities within the current and future NIH
Roadmap initiatives. NINR is already supporting important
interdisciplinary research training and interdisciplinary research,
including community-based research. NINR's scientific community has
been alerted to the procedural changes that need to take place in order
to capitalize on the NIH Roadmap initiatives; their enthusiasm predicts
a high level of support for the Roadmap.
From its inception, NINR has emphasized interdisciplinary research
teamwork and clinical and translational research, which are prominently
featured in the Roadmap agenda. Our studies address national health
problems head on. We have moved from an acute to a chronic disease
focus, with emphasis on older people, who are living longer with
illness and want the highest quality of life possible. We promote
ethnically and culturally sensitive research and are aggressively
pursuing research on health disparities, devoting about 20 percent of
our budget to this area of science.
control of high blood pressure in young inner-city african-american men
A good example of a program of research that improves health care
disparities in a vulnerable African-American population is located a
short distance from here--East Baltimore. The number of people with
hypertension nationally is 40 percent higher for African-Americans than
for Caucasians, and there is more severe disease impact among African-
Americans that can include heart enlargement and kidney dysfunction.
The Johns Hopkins School of Nursing conducted this unique hypertension
study, targeting a high-risk population of hypertensive young African-
American men between 21 and 54 years of age who are generally
considered underserved by the healthcare system. At the study's start,
only 17 percent had control of their blood pressure, but after three
years, 44 percent of the men receiving the intensive form of a
carefully designed community-based intervention attained control of
their blood pressure. In some cases, the study represented the first
time the study participants experienced formal healthcare. Of special
significance is that 90 percent of the young men were retained in the
study for the entire three-year period. A key to this success was the
culturally appropriate, multidisciplinary research team approach that
involved nurse practitioners, community health workers, and physicians.
Among the lessons learned from this research is the need to modify
healthcare for vulnerable populations like this one in Baltimore--
health care that involves home visits that offer educational and
behavioral counseling to supplement visits to the clinics, and
addresses factors beyond the disease itself, such as reducing substance
abuse and obesity.
HEALTH OF MINORITY, INNER CITY NEWBORNS IMPROVED BY NURSE HOME VISITS
Another example of a health disparity is infant mortality, with
rates for African-Americans twice those of Caucasians. Researchers
tested a carefully designed intervention tailored to the risks of the
populations studied to help close this health disparity gap. Findings
after one year of the project indicate that the health outcomes of both
mother and infant were improved, and costly health care was avoided.
The intervention involved focusing on low-income, pregnant African-
American and Mexican-American mothers from the inner city, who received
a program of planned prenatal care and post-natal monitoring with
teaching and counseling at each encounter. Home visits made by a team
of trained community residents and led by a nurse were an important
feature, and the mothers received monthly phone calls for a year after
their babies were delivered. The effects of the program varied by race
and ethnicity. For African-Americans, findings indicated that mothers
had more realistic expectations of their parenting role and were able
to document the immunization of their infants. Their infants' mental
development scores were higher than the control group. Mexican-American
mothers showed improved skills in dealing with everyday life and in
playing with their infants. This research and previous studies indicate
that home visits by a nurse-health advocate team are among the most
successful interventions in improving maternal and infant health--even
for-inner city, low-income minority families. The key is to implement
culturally sensitive interventions that are intensive and adequately
staffed and funded.
WOMEN'S EARLY WARNING SIGNS OF HEART ATTACK
Although heart disease is the number one cause of death in both
genders, far less is known by physicians and by women themselves about
how women experience the disease. Research focusing on women's symptoms
prior to heart attack found that women have different early warnings of
heart attach than men have. Of note is that most clinicians consider
chest pain as the most significant symptom for both sexes. Yet in this
study the most prevalent symptom was reported to be unusual fatigue (70
percent), followed by sleep disturbance (48 percent), and shortness of
breath (42 percent). Fewer than a third of the women reported chest
pain or discomfort. Even during the heart attack, 43 percent did not
experience chest pain. Clearly, women's symptoms appear to be different
from men's. This underscores the importance of women and clinicians,
both, recognizing early warning signs of impending heart attack in
women, so that they can prevent it or ease its effects.
CHOLERA REDUCED BY LOW TECH WATER FILTRATION
A growing global problem faced by developing nations is the
availability of healthy drinking water, a most basic need for life and
health. Cholera is carried by untreated surface water and kills
thousands of people around the world by causing severe vomiting and
diarrhea. The World Health Organization reports that the number of
countries with cholera is increasing. In our own hemisphere, cholera
incidence is now increasing in 16 Latin American nations. Researchers
in Bangladesh have found a simple preventive technique that works and
may be transferable to other countries. Inexpensive and widely
available cotton sari cloth, when folded four to eight times, creates a
filter small enough to remove most plankton, where cholera bacteria
often live. In 65 villages with 133,000 inhabitants, the number of
cholera cases was almost cut in half when people filtered their water
with the sari cloth. Cultural barriers were not an issue, and about 90
percent of the rural study participants followed the filtering
procedure. When cholera did occur, those villagers had drunk unfiltered
water at villages not participating in the study. The sari filtering
technique could work just as well using other types of inexpensive
cloth filters if replicated in countries where cholera is widespread.
THE NINR ROLE IN THE NIH ROADMAP
Last year, NINR developed what we call Research Themes for the
Future, which represent NINR priorities over the next five plus years.
These themes blend well with the NIH Roadmap overall, especially in two
areas--Interdisciplinary Research Teams of the Future, and Re-
engineering the Clinical Research Enterprise. In the first area, NINR
has considerable experience carrying out interdisciplinary team
research projects. In fiscal year 2003, more than half of NINR
investigator publications appeared in non-nursing journals. This
underscores the promise of future successful interdisciplinary research
and practice collaborations. It also indicates that many other
disciplines value nursing research findings. In the area of improving
the clinical research enterprise, most of NINR's research is clinical
in nature and can bring research questions to the laboratory from the
clinical researcher's perspective. Investigators also translate
research findings into the clinical practice of healthcare providers
and develop partnerships with communities to speed new scientific
knowledge into mainstream health regimens. Late last year, NINR
supported a national conference to promote research-intensive
environments in clinical settings, including academic medical centers
and those that are nontraditional as far as research is concerned, such
as nursing homes and community-level health enterprises. The goal was
to create partnerships between academic researchers and potential
investigators in these settings to develop resources and ease barriers
to innovative research.
To make the Roadmap a reality for nurse researchers, since the
Roadmap will not be business as usual, but business as usual plus, NINR
recently convened an implementation meeting with interdisciplinary
experts from across the country. The meeting addressed ways to
intersect NINR's themes and priorities with those of the Roadmap, as
well as suggestions for new Roadmap directions that reflect the
expertise of nursing research. Since NINR has always stressed
interdisciplinary research, we look forward to increased participation
in the Roadmap.
INITIATIVES
Looking ahead to our fiscal year 2005 initiatives, reduction of
obesity, a major public health issue, is certainly on the NINR agenda.
Pediatric and adolescent obesity is particularly disturbing in and of
itself, because it forewarns of future poor health. We plan to target
minority populations at risk for obesity and children who are
underserved--for example, those in rural areas. Research will address
biological, behavioral and social science factors leading to or
perpetuating obesity.
Our genetics initiative is novel for NINR, since it involves
incorporating behavioral, biological and molecular science into nursing
research. Our focus will be on the interactions between genes,
environment and behavior, including health promotion behavior. We will
also assess the results of genetic education and counseling, and the
effects of genetic testing on health, including lifestyle changes and
the reduction of risks for disease.
Increased attention is required to build the knowledge base for
effective end of life care. NINR is the lead Institute at NIH for end-
of-life research. The research agenda we have identified for better
healthcare management at this final stage of people's lives includes
improved methodology, instruments, communication, and interventions
that helped making choices. Previously published NINR-funded research
findings on symptom management are already being integrated into
standards of care. Further study is taking place to develop new
behavioral approaches to improve the lives of patients and their
caregivers and to devise new techniques to improve management of pain.
Self-management has become the most basic way people can improve
their lives when they are living with long-lasting, incurable chronic
illness. Successful self-management interventions tested in mainstream
populations, such as how to improve coping skills and how to maintain
and improve cognitive functioning, will be tested in populations with
special needs: the unemployed, homeless, very old, impoverished,
disabled, or geographically isolated.
Another initiative involves symptom management. Traditionally,
clinical practice treats symptoms one symptom at a time. Yet symptoms
rarely occur alone they occur in clusters. NINR plans to support
research that will identify and describe groups of symptoms in HIV/AIDS
and cancer patients by determining these clusters' effects on the
patient, and developing interventions to manage the multiple symptoms.
In addition to assisting how one symptom impacts the others in a
cluster, we will consider the effects of age, treatment, gender, and
type and stage of disease.
NINR will expand on past and current research initiatives that
focus on minority and underserved women's health, such as health
disparities and reduction of low birth weight among minority women. The
new initiative will focus on other aspects of women's health outside of
reproduction, which in the past was frequently the central focus of
women's health research by investigators of many disciplines.
INCREASING THE NUMBER OF NURSE INVESTIGATORS
The well documented and current shortage of nurses was preceded by
a significant shortage of nurse researchers. The shortage of nurse
researchers also means fewer nursing faculty to train future nurses and
to conduct research that provides the scientific base for healthcare
practice. In confronting this issue, NINR continues to collaborate with
universities nationwide to rapidly develop baccalaureate-to-doctoral
fast-track programs. This is in response to one of the recommendations
of the National Research Council four years ago, which urged
preparation of more nurse researchers more quickly. NINR revised the
predoctoral training mechanism to enable nurses to enroll in the many
fast-track doctoral programs in nursing which accept baccalaureate-to-
doctoral students. NINR has been responsive to the National Research
Council's recommendation, and the nursing community has also responded
by rapidly developing these baccalaureate-to-doctoral programs all over
the nation.
NINR supports Developmental and Core Centers to stimulate research
and research training opportunities. Creating partnerships and
leveraging funds is a hallmark of those Centers. We also initiated 17
Nursing Partnership Centers to Reduce Health Disparities, in
collaboration with the National Center on Minority Health and Health
Disparities. These Centers partner eight research-intensive
universities with nine minority-serving institutions. As a result of
this program, we expect health disparities research to expand and the
number of minority nurse investigators to increase.
NINR will continue to offer career development awards, and we will
make a special effort to train minority investigators through mentored
research scientist awards and research supplemental awards. NINR's
small but growing intramural research program is initiating a graduate
partnership program with universities across the country this year and
continues to support postdoctoral training opportunities on the NIH
campus.
In closing, the upcoming year contains new opportunities to
configure scientific research in new ways. NINR and the nursing
research community look forward to participation in the NIH Roadmap
initiative and in other research that directly impacts the improvement
of people's health.
Thank you, Mr. Chairman. I will be pleased to answer any questions
the Committee might have.
______
Prepared Statement of Dr. Barbara Alving
I am pleased to present testimony before this Committee on behalf
of the National Heart, Lung, and Blood Institute (NHLBI).
The NHLBI leads a national program directed at alleviating the
burdens of diseases of the heart, blood vessels, lungs, and blood. The
Institute also is responsible for research on the clinical uses of
blood and its products and the management of blood resources. For more
than a decade, the National Center on Sleep Disorders Research has been
part of the NHLBI and, since fiscal year 1998, the NIH Women's Health
Initiative has been administered by the Institute. Our diseases and the
burdens associated with them touch the lives of all Americans.
BASIC AND CLINICAL RESEARCH APPROACHES
The ultimate goal of the NHLBI is to improve the public health
through discovery of effective methods to prevent and treat disease.
Progress toward this goal depends on the existence of a coordinated
program that focuses on clinical investigation as the culmination of
basic research to unravel the fundamental processes that govern health
and disease. The Institute has fostered and sustained a longstanding
commitment to laboratory investigations of relevance to its mandate.
Moreover, in recent years it has allocated a significant share of the
generous budget increases provided to it to aggressive pursuit of
promising, cutting-edge opportunities in such disciplines as genomics,
proteomics, and nanotechnology. Advances in these areas promise to
enable, among other things, more specific approaches to health
promotion based on detailed assessment of individual characteristics
rather than on general observations about what does or does not foster
good health. Our optimism about the probable yield of these new
endeavors cannot be overstated.
However, the health-related outcomes of these basic science
endeavors depend greatly on the extent to which laboratory discoveries
are translated into approaches applicable to ``real-life'' health
problems. And that, in turn, depends on clinical research. Being a
disease-oriented agency, the NHLBI has for many years placed strong
emphasis on developing and maintaining a robust clinical research
portfolio. Particularly with regard to clinical trials, the Institute
has worked to design efficient, less costly research approaches to
evaluating therapeutic and preventive strategies. As part of this
effort, the NHLBI has developed and refined the ``clinical research
network'' concept and successfully applied it to evaluate new
therapeutic approaches to conditions such as pediatric cardiovascular
disease, asthma, acute respiratory distress syndrome, and Cooley's
anemia. The networks provide an infrastructure that enables rapid and
cost-effective testing of new therapies as they come to light.
THE NIH ROADMAP--CLINICAL RESEARCH
It naturally follows that the NHLBI is an enthusiastic participant
in the NIH Roadmap initiative titled Re-Engineering the Clinical
Research Enterprise: Feasibility of Integrating and Expanding Clinical
Research Networks. This new solicitation seeks to identify ways in
which clinical research networks can collaborate to conduct clinical
trials and other multicenter clinical research studies more efficiently
than the current system allows. We at the NHLBI believe that
application of lessons learned from this Roadmap initiative will better
position the Institute to accelerate the pace of research and to reduce
barriers that prevent research advances from becoming incorporated into
clinical practice.
POSTMENOPAUSAL HORMONE THERAPY
Major unexpected findings from the NIH Women's Health Initiative
(WHI) illustrate the critical importance of the randomized, controlled
clinical trial in determining the risks and benefits of preventive
strategies. The study, which assessed the role of estrogen therapy,
with or without added progestin, in preventing major causes of death
and disability among postmenopausal women, was predicated on strongly
suggestive evidence from basic research, observational studies, and
smaller clinical trials that often measured so-called surrogate end
points (e.g., changes in heart disease risk factors or subclinical
manifestations), rather than events such as heart attacks or deaths
from coronary disease. Indeed, at the outset of the WHI, much doubt
existed regarding the feasibility and ethics of conducting the trial,
because ``everybody'' already ``knew'' that hormone therapy helped
women remain youthful and ``feminine forever,'' by not only relieving
troublesome menopausal symptoms but also improving general health. Much
to the surprise of researchers, practicing physicians, and women
themselves, the trial of estrogen plus progestin last year was halted
when it found increased risks of heart attack, stroke, invasive breast
cancer, and blood clots among women assigned to take hormones. And
quite recently, the estrogen-alone part of the study was discontinued
because the hormone did not appear to have the hoped-for beneficial
effect on heart disease (or, on the other hand, the feared unfavorable
effect on breast cancer), but it did increase risk of stroke. These
findings have major public health significance: the conclusion is that
postmenopausal hormones, once ranking among the most-prescribed
preparations in the United States, should generally be used only for
short-term alleviation of menopausal symptoms.
LUNG-VOLUME-REDUCTION SURGERY (LVRS)
Another trial of great practical importance was a rigorous
assessment of LVRS, a procedure that was first used to treat emphysema
during the 1950s. Although some patients seemed to benefit from this
radical and invasive procedure, high mortality and morbidity
discouraged its widespread use until the early 1990s, when some
surgeons began performing LVRS again and insurance reimbursement became
one of several issues demanding resolution. The National Emphysema
Treatment Trial (NETT) clarified the short-and long-term risks and
benefits of LVRS and identified the characteristics of patients who may
be most likely to benefit from LVRS, as well as those who are at
greater risk of death and complications from the procedure. The NETT
reflects a unique relationship in which the NIH funded and administered
the study and the Centers for Medicare and Medicaid Services (CMS),
which sought evidence regarding the advisability of providing Medicare
reimbursement for LVRS, supported participants' care costs.
Additionally, the Agency for Healthcare Research and Quality
contributed support for analysis of the cost-effectiveness of LVRS. The
study results have provided a scientific basis for reassessment of
Medicare coverage for LVRS.
TRIALS OF HYPERTENSION CONTROL AND PREVENTION
Last year, we reported results from the ALLHAT (Antihypertensive
and Lipid-Lowering Treatment to Prevent Heart Attack Trial), which
found persuasive evidence that traditional diuretics should be the
initial treatment of choice for lowering high blood pressure. This is a
study that only the NIH would likely have undertaken, as the comparison
drugs--a calcium channel blocker and an ACE (angiotensin-converting
enzyme) inhibitor--were already established as blood-pressure-lowering
agents; it further illustrates the unique role played by the NIH in
addressing issues of public health importance. Of additional interest
is the observation that blood pressure control rates among ALLHAT
participants increased from 25 percent at the beginning of the ALLHAT
to 66 percent after five years of followup. These gains were achieved
in a variety of clinical practice settings and in subgroups of people
known to experience difficulty with blood-pressure control, such as
blacks, the elderly, and diabetic patients. These results offer
encouragement that blood pressure control is obtainable, and they
challenge us to pursue this goal vigorously.
The ALLHAT findings, in combination with evidence from other
research studies, prompted issuance of an updated set of guidelines for
hypertension management--the so-called JNC 7, or Seventh Report of the
Joint National Committee on Prevention, Detection, Evaluation, and
Treatment, of High Blood Pressure. An important feature of the
guidelines is a reclassification of blood pressure levels that includes
the new category ``prehypertension'' (120 to 139 mm Hg systolic and/or
80 to 89 mm Hg diastolic blood pressure). Individuals with
prehypertension are strongly encouraged to pursue lifestyle changes--
losing excess weight, eating a heart-healthy diet, increasing physical
activity, quitting smoking--to forestall development of overt
hypertension. To date, most behavioral interventions have focused on
only one or two lifestyle changes at a time. However, findings from a
recent clinical trial indicate that an all-in-one approach to lifestyle
changes is feasible and effective in lowering blood pressure. Trial
participants who addressed many elements of a healthy lifestyle
simultaneously also significantly reduced their weight and became more
fit providing even more incentive to undertake such changes.
HYDROXYUREA THERAPY FOR SICKLE CELL DISEASE
A breakthrough for patients occurred in 1995 when the NHLBI
announced the results of a major trial of the first treatment for
adults with sickle cell disease. The study found that use of the drug
hydroxyurea slashed rates of painful crises and acute chest syndrome,
and sharply reduced the need for blood transfusions and
hospitalizations. A followup study of the trial participants recently
reported that hydroxyurea not only protects patients from episodes of
severe illness associated with their disease, but also prolongs their
lives. Even the sickest patients--those who suffered three or more
painful crises a year--benefitted. These results have important
implications both for improving patient care and for decreasing health
care costs associated with sickle cell disease.
IMPROVING SURVIVAL FOR VICTIMS OF CARDIAC ARREST
Cardiac arrest--in which the heart stops beating effectively, blood
does not circulate, no pulse can be felt, and the victim collapses into
unconsciousness--is a frequent occurrence in this country. Despite
several decades of efforts to train members of the public to perform
CPR (cardiopulmonary resuscitation), few victims of out-of-hospital
cardiac arrest survive the experience. The NHLBI Public Access
Defibrillation trial trained volunteer rescuers to use an automated
external defibrillator, a device that shocks the heart back into normal
rhythm. It found that use of CPR plus the defibrillator, compared with
use of CPR alone, markedly increased survival of people who suffered
cardiac arrest in various community settings, and caused no major
injuries or serious safety problems. An important next step, currently
under way with NHLBI support, is to determine the safety and
effectiveness of providing defibrillators to families of heart attack
patients for use when a cardiac arrest occurs at home. In addition, the
Institute is establishing a research consortium of investigators,
hospitals, emergency medical services, and local communities to
investigate promising experimental strategies to resuscitate patients
who experience out-of-hospital cardiac arrest.
COMBATING THE OBESITY EPIDEMIC
Obesity is a problem of great concern to the NHLBI, as it strongly
influences the risk for developing diseases and conditions such as
coronary heart disease, hypertension, and diabetes. Thus, the Institute
is strongly involved in the overall NIH effort to reverse the U.S
obesity epidemic, and I have been especially pleased to serve as
cochair of the NIH Obesity Research Task Force.
The NHLBI recently launched a major study that addresses one of the
most challenging aspects of weight control--keeping lost pounds off.
The Weight Loss Maintenance Trial will initially assist overweight or
obese adults participants in making lifestyle changes to reduce their
weight and, subsequently, it will test various strategies to help the
participants maintain their weight loss over the next several years.
The trial focuses on persons who are being treated for high blood
pressure or high blood cholesterol and, consequently, have particularly
strong reasons to achieve and maintain a healthy weight.
Another new initiative will assess the effectiveness of worksite
interventions for preventing or controlling overweight and obesity in
adults. Strategies to be considered include implementing environmental
and policy changes to increase employees' physical activity (e.g.,
flextime or fitness-center discounts), offering healthful food choices
in cafeterias and vending machines, providing information about
nutrient and calorie content of foods at the point of purchase, and
enhancing social support from fellow workers to encourage improved diet
and physical activity.
A third NHLBI initiative will explore the potential use of
bioengineering approaches to address problems of obesity. For example,
new methods for imaging body fat content may enable more specific
identification of who needs to lose weight and their success in doing
so. Bioengineering techniques may also offer a solution to the
difficult technical challenge of obtaining precise measurements of
energy intake and expenditure. One can envision development of a
wristwatch-like gadget from which the wearer could easily determine
whether an energy intake goal has been exceeded or an energy
expenditure has been met. New approaches might provide accurate,
convenient, easily understood, and inexpensive devices that would
foster research, improve clinical management of adults and children,
and help the public eat less and exercise more.
CONCLUSION
These examples illustrate the extraordinary potential of clinical
research, and particularly clinical trials, to address issues of major
importance to the public health. The NHLBI will continue its commitment
to stimulate and support clinical research, and to ensure that the
knowledge thereby gained is rapidly, efficiently, and fully applied to
disease treatment and prevention.
BUDGET STATEMENT
The fiscal year 2005 budget includes $2,963.9 million, an increase
of $172.1 million over the fiscal year 2004 enacted level of $2,791.8
million.
I would be pleased to answer any questions that the Committee may
have.
______
Prepared Statement of Dr. James F. Battey, Jr.
Mr. Chairman and Members of the Committee, I am pleased to present
the President's budget request for the National Institute on Deafness
and Other Communication Disorders (NIDCD). The fiscal year 2005 budget
includes $393,507,000 which reflects an increase of $11,561,000 and a 3
percent increase over the fiscal year 2004 final conference level.
Disorders of human communication exact a significant economic, social,
and personal cost for many individuals. The NIDCD supports research and
research training in the normal and disordered processes of hearing,
balance, smell, taste, voice, speech, and language. NIDCD's mission
includes the support of research to create assistive devices which
substitute for lost and impaired sensory and communication function.
Equally important to the NIDCD mission has been the discovery of
genetic mutations that affect communication disorders. This work would
not have been possible without the completion of the Human Genome
project, supported in part by the National Institutes of Health.
Enabled by this landmark accomplishment, scientists supported by the
NIDCD have been studying the genes responsible for non-syndromic (not
associated with any other problem) hereditary hearing impairment.
Within the last 8 years, 54 genes have been identified, largely due to
the contributions of NIDCD. Scientists are now focusing their efforts
on identifying more genes, learning what role the genes have in
deafness, and determining which genes affect certain populations of
individuals. For example, recent studies have demonstrated that
particular ethnic groups carry specific genetic mutations. Studying the
genes that cause non-syndromic hereditary deafness will also permit
early and more accurate genetic testing and foster the development of
innovative intervention and prevention strategies, and more effective
treatment methods for individuals with deafness and other communication
disorders. My testimony today will primarily focus on the many genetic
discoveries that have allowed NIDCD-supported scientists to learn more
about the causes of communication disorders, a first step in prevention
and treatment.
NEW WAY TO IDENTIFY USHER SYNDROME IN CHILDREN
Usher syndrome Type 1 is an inherited disorder. Children born with
this disorder are deaf, suffer balance problems, and gradually lose
their vision. Although Usher syndrome affects individuals of other
racial and ethnic backgrounds, scientists have recently identified a
clear pattern of its inheritance in Ashkenazi Jews, who are descendants
of Jews from Germany, Austria and Eastern Europe. In 2003, a NIDCD-
supported scientist identified a mutation within the gene known to be
responsible for Usher syndrome. The particular mutation seems to be
responsible for most of the Usher syndrome seen in Ashkenazi Jews.
Because scientists now know which mutation is responsible for this type
of Usher syndrome, they can develop genetic tests to detect the
mutation in Ashkenazi Jewish children who are born deaf. By identifying
children destined to lose their sight, parents and doctors can help
them learn to communicate and prepare them for blindness. Some of these
children will be appropriate candidates to receive a cochlear implant.
Cochlear implants are small electronic devices that enable individuals
who are deaf or have severe hearing loss to detect sound. This research
will now enable doctors to provide important quality of life
improvements for children with Usher syndrome.
GENE REPLACEMENT THERAPY CAN GENERATE NEW HAIR CELLS
The sensory hair cells of the inner ear play an important role in
detecting sound. People who lose hair cells due to excess noise,
infections, or accidents often lose some or all of their ability to
hear. Scientists have determined that many forms of inherited deafness
are also due to problems with hair cells. The hair cells of the inner
ear act like miniature amplifiers. Sound waves that enter the inner ear
are converted into a series of chemical and electrical signals within
the cells. These signals are ultimately transmitted to the brain via
the auditory nerve and interpreted as sound. In the past, only birds or
reptiles were thought to be capable of generating new hair cells. Now,
NIDCD-supported scientists have discovered a way to use gene therapy to
generate new hair cells in the ears of adult mammals. Scientists used a
virus to transfer a gene called Math1 into the ears of guinea pigs.
Math1 is expressed in developing hair cells, and its expression is
thought to cause the cells to become hair cells, rather than becoming
another cell type within the ear. The virus infects cells of the ear
and causes them to produce the Math1 protein. Early experiments suggest
that when the virus infects cells that do not normally express Math1,
some of these cells become hair cells. In addition, the new hair cells
also attract fibers of the auditory nerve, suggesting that the new
cells may also be able to establish a link to the part of the brain
that interprets sound--the auditory cortex. If this work can be
duplicated in human beings, it may be the first step towards enabling
scientists to use gene therapy to restore hearing to those who have
lost it, or to enable deaf individuals to hear.
NEW SHORT ELECTRODE WILL ALLOW GREATER BENEFIT FROM COCHLEAR IMPLANTS
Cochlear implants are commercially available miniature hearing
prostheses capable of assisting those who are profoundly deaf or
severely hearing impaired. Approximately 60,000 individuals all over
the world have received cochlear implants. The implant bypasses damaged
or missing hair cells to send electrical signals through an array of
electrodes within the cochlea (inner ear). Current cochlear implants
send sound information that covers the entire frequency range. In order
to send both high and low frequency information, the electrodes of the
cochlear implant are inserted as far into the cochlea as possible.
Unfortunately, inserting the electrodes into the cochlea compromises
any residual (remaining) hearing the individual may have had prior to
implantation. Consequently, scientists developed a new shorter
electrode to help an additional population of individuals with hearing
loss. These individuals have a considerable amount of residual hearing
and their primary hearing loss is in sounds in the high frequency
range. They are also experienced, yet unsuccessful, adult hearing aid
users with severe-to-profound hearing impairment who would not have
been conventional cochlear implant candidates. The short electrode is
inserted into the base (or bottom) of the cochlea to restore hearing at
high frequencies, while preserving low frequency hearing, or residual
hearing, in the apex (or top) of the implanted ear.
The preliminary data demonstrates residual hearing can be preserved
with this short electrode, and provides evidence that this is most
beneficial for understanding speech in a noisy background. Furthermore,
the innovative short electrode may be an ideal treatment for those with
presbycusis, which is the loss of hearing that gradually occurs in most
individuals as they grow older. This new electrode design allows many
more people with some degree of hearing loss to benefit from cochlear
implant technology.
IDENTIFYING GENES IMPORTANT FOR THE SENSE OF TASTE
The worldwide obesity epidemic is causing health professionals to
focus their attention on how people choose which foods to eat. Because
taste plays an important role in food choice, scientists are interested
in figuring out how taste buds tell the brain that they have tasted
something, and which taste genes are responsible for sensing different
food flavors. Vegetables such as broccoli, cauliflower, cabbage, and
brussels sprouts contain compounds related to phenylthiocarbamide
(PTC). For more than 50 years, scientists thought that the ability to
taste PTC and similar compounds was determined by a single gene. If an
individual inherited the PTC-tasting version of the gene, then they
detected its bitter taste. If the tasting version of the gene was not
inherited, the compound had no taste to that individual. Now NIDCD
scientists, in collaboration with scientists in California and Utah,
have identified a gene that regulates a person's sensitivity to the
bitter taste of PTC. This explains why people seem to demonstrate a
range of sensitivity to PTC's taste and may even influence whether or
not an individual likes to eat broccoli and other vegetables containing
PTC-like compounds. Because they determine an individual's sensitivity
to a particular taste, inherited genes probably influence food choices.
In the future, doctors may now be able to use this knowledge as part of
a strategy to prevent and treat obesity and to overcome poor nutrition
due to poor food choices. Increased knowledge about how taste cells
tell the brain that they have detected a particular flavor may also
help doctors restore the sense of taste to those who have lost it due
to injury, disease or aging.
VOCAL FOLD PARALYSIS
Vocal fold paralysis is a genetic disorder that can be inherited.
The vocal folds are two bands of smooth muscle tissue that lie opposite
each other and are located in the larynx or voice box. When at rest,
the vocal folds are open to allow an individual to breathe. Voice is
produced by vibration of the vocal folds. To produce voice, air from
the lungs passes through the folds, causing vibration and thus making
sound. The sound from this vibration then travels through the throat,
nose, and mouth (resonating cavities). The size and shape of these
cavities, along with the size and shape of the vocal folds, help to
determine voice quality. Paralysis of the vocal folds impacts voice
quality and inhibits an individual's ability to communicate. This
disorder can also cause life-threatening breathing difficulties in
affected newborn infants.
Intramural scientists at the NIDCD and the National Institute of
Neurological Disorders and Stroke are studying a family in which this
disorder occurs and have found that vocal fold paralysis is due to
degeneration of the nerves involved in movement. Weakness in the
muscles of the arms and legs can also accompany this disorder. In the
study, genetic analyses were used to locate the site of the causative
gene to a section on chromosome 2. Further studies revealed that
mutations in the dynactin gene, which resides at this location, are
responsible for this disorder. Dynactin is a molecule that helps
transport materials within nerve cells, and this research finding
suggests that dynactin transport is essential for health and
maintenance of at least some motor nerve cells.
This finding allows for a genetic tool for diagnosing vocal fold
paralysis, which can aid in the clinical and neonatal management of
this disorder. In addition, these findings provide better understanding
of motor nerve cells and the molecular mechanisms that cause motor
nerve degeneration.
NIH ROADMAP
The NIH Roadmap initiative to support interdisciplinary research
and research training will advance the NIDCD mission because it
encourages collaboration of scientists from seemingly unrelated
disciplines. Interdisciplinary collaborations from a variety of
scientific disciplines are necessary for developing assistive
communications devices such as hearing aids and cochlear implants. The
success of the development of the cochlear implant is a good example of
successful interdisciplinary research as it involved the effort of
physicists, chemists, material scientists, psychologists
otolaryngologists, audiologists, speech-language pathologists,
electrical engineers, and biomedical engineers We look forward to
expanding upon that type of research in the coming years.
Finally Mr. Chairman, I would like to thank you and Members of this
Committee for giving me the opportunity today to speak to you about the
exciting recent discoveries from the NIDCD. I am pleased to answer any
questions that you have.
______
Prepared Statement of Dr. Donald A.B. Lindberg
Mr. Chairman and Members of the Committee: I am pleased to present
the President's budget request for the National Library of Medicine
(NLM) for fiscal year 2005, a sum of $325,147,000, which reflects an
increase of $16,671,000 over the comparable fiscal year 2004
appropriation.
The National Library of Medicine continues to be the premier source
of science-based medical information. Just 10 years ago the Library
introduced its Web site one of the very first in the federal government
and so began a decade of amazing growth in the amount and variety of
medical information it made available. Today the Library's Web service
not only provides free access to Medline/PubMed, the largest and most
reliable database of scientific medical information in the world, but
NLM has created information products designed specifically for
patients, families, and the public.
Despite its recent successes, NLM believes that the surface has
barely been scratched and that the future holds the promise of many
more valuable information products for the professions and the public.
The Library's communications experts are at the cutting edge of new
technology and, as more and more users have access to ever more
powerful networks, the Library will put in place sophisticated yet easy
to use information services that allow users free access to the world's
burgeoning base of science-based health information. For scientists
this means access not only to the growing published journal literature,
but also electronically to scientific monographs and textbooks and to a
variety of genomic information resources through NLM's National Center
for Biotechnology Information (NCBI). For the general public, this
means making even more consumer health information--from the National
Institutes of Health and other reliable sources--available from the
NLM's Web site.
The new NIH Roadmap Initiative has the potential to have a profound
and positive impact on how American medical research is conducted. The
NLM sees itself has having an important role in the Initiative in three
areas. Because the Roadmap recognizes that one of the most powerful and
unifying concepts of 21st century biology is that of bioinformatics,
the computerized bioinformatics databases and analysis tools of the
NCBI will become even more central to the research enterprise. Second
is the Roadmap's requirement to ``re-engineer the national clinical
research enterprise.'' NLM's leadership role in working with biomedical
vocabularies the Unified Medical Language System, the recently
announced arrangement with the SNOMED clinical vocabulary, and NLM's
expanding the NIH clinical trials database are all key aspects of
improving clinical research. Finally, the Roadmap articulates NIH's
responsibility to communicate research results to improve the quality
of life for all people. The Library has a central role in collecting
and communicating these results through Web-based information services
and online databases. These are described in what follows.
TOOLS FOR SCIENTISTS AND HEALTH PROFESSIONALS
The NLM's Medline/PubMed is the most-used database of peer-reviewed
medical information in the world. It contains more than 12 million
references and abstracts to the world's medical literature published
since the 1960s; an ancillary ``OldMedline'' extends the coverage back
to the early 1950s. Each year millions of scientists and health
professionals connect to Medline/PubMed (no registration or fee is
required) and search for information they can use in the research or
practice. More than a half billion such searches are done every year.
The newest system, introduced in 1997, is constantly being improved.
Several years ago NLM introduced links between Medline/PubMed
references and publisher websites so users could retrieve the full text
of articles. Today, more than 4,000 of the database's 4,600
publications have such links.
Another heavily used database is GenBank, the repository of all
publicly available DNA sequences sent to the NLM from laboratories
around the world. GenBank, and an increasing array of other valuable
data resources, is the responsibility of the National Center for
Biotechnology Information. The Center, which was created by the
Congress in 1988 with the mandate to manage and disseminate genetic
data, coordinates closely with the NIH Human Genome Project. GenBank
today contains more than 27 million sequence entries totaling 33
billion base pairs from over 130,000 species. NLM, through the Web
operations of the NCBI, receives more than a quarter million visitors a
day seeking molecular biology information ranging from DNA sequences
and protein structures to the related research literature.
A repository for chemical structure and assay data has been
suggested as one aspect of NLM's involvement with the NIH Roadmap
Initiative on ``small molecules'' to enhance research and develop new
therapies. The NCBI is working on such a repository--called PubChem--
which will integrate into one open database, information from existing
chemical structure databases at various NIH institutes as well as data
supplied from industry and academic centers. By providing chemical
structure validation and structure-structure matching and by linking to
descriptions of the compounds in journal articles, PubChem will play an
invaluable role in making this information useful to scientists.
PubMedCentral, a digital archive, is an important component of the
infrastructure needed to enhance access to the life sciences
literature. Publishers electronically submit peer-reviewed research
articles, essays, and editorials. NLM guarantees free access to the
material; copyright remains with the publisher or the author. Access to
PubMedCentral is free and unrestricted. The full text of more than 100
life science journals, some going back decades, is now available, and
more are added as they sign on to the system. Digitally archiving the
scientific literature and guaranteeing access for future generations is
an important NLM responsibility.
INFORMATION SERVICES FOR THE PUBLIC
The National Library of Medicine has become a favorite destination
of seekers of health-related information on the Web--people looking for
answers to questions about their health or the health of their loved
ones. MedlinePlus, the largest of NLM's Web offerings for the general
public, now receives about 4 million unique visitors a month.
Increasingly, they also find their way on the NLM Web site to other
services created specifically for them--NIHSeniorHealth.gov,
ClinicalTrials.gov, Genetics Home Reference, Household Products
Database, and Tox Town are all recent examples. These Web sites contain
or point to information created by NIH components and other reliable
noncommercial sources. They require NLM librarians and information
specialists to work closely with a wide variety of outside
organizations. MedlinePlus, launched in November 1998, today is one of
the most heavily trafficked Web sites containing health information for
the public. It has more than 650 ``health topics,'' containing, for
example, overview information, pertinent clinical trials, alternative
medicine, prevention, management, therapies, the latest research, and
the latest news from the print media. There are even links to the
scientific literature through Medline/PubMed. In addition to the 650
health topics, there are medical dictionaries, encyclopedias,
directories of hospitals and providers, and interactive ``tutorials''
with images and sound. MedlinePlus en espanol was introduced in 2002
and has grown to virtual parity with the English version. Both scored
the highest marks of any Federal Web site in a recent outside
evaluation. A new aspect of MedlinePlus is its plan to ``Go Local,''
that is, to link users with community helping services near them. North
Carolina is the first MedlinePlus partner to go local.
The National Library of Medicine is collaborating with the American
College of Physicians in a unique ``Information Rx'' project that seeks
to encourage practicing physicians who are members of the College to
``prescribe'' MedlinePlus to their patients who need further
information on a medical subject. After test runs in Georgia, Iowa,
Virginia, and Florida, the Information Rx program will go nationwide
later in 2004.
MedlinePlus is not the only NLM information service directed at the
consumer. Another very popular resource is ClinicalTrials.gov, which
integrates previously fragmented information on human studies for
different conditions into a single, coherent system, providing the
public with an easy-to-use and convenient ``one-stop'' site for
comprehensive information on clinical trials. The site, which is used
not only by the public but by their health care providers, currently
includes information on approximately 8,800 trials for hundreds of
diseases and conditions conducted in about 90 countries.
ClinicalTrials.gov receives approximately 16,000 visitors daily and
over 3 million page views monthly.
Late in 2003 another service for the public was launched:
NIHSeniorHealth.gov. This site contains information in a format that is
especially usable by seniors. For example, the site features large
print and easy-to-read segments of information repeated in a variety of
formats--such as open-captioned videos and short quizzes to increase
the likelihood it will be remembered. NIHSeniorHealth.gov has a
``talking'' function, which allows users the option of reading the text
or listening to it as it is read to them. Another new NLM consumer
service is the Household Products Database. This is a guide that
provides easy-to-understand information on the potential health effects
of more than 2,000 ingredients contained in more than 4,000 common
household products. The database provides information on many of these
substances and their potential health effects, in consumer-friendly
language. For more technical information, users can launch a search for
a product or ingredient from the product's page into NLM's TOXNET, a
cluster of databases on toxicology, hazardous chemicals, and related
areas.
Another consumer health information resource introduced in 2003 is
the Genetics Home Reference. Genetics is a complex subject, and much of
the primary data and literature are difficult to understand without
formal training. The Genetics Home Reference Website augments
MedlinePlus with summaries of genetics information and an overview of
the fundamentals of genetic science. The user can browse by a specific
disease/condition or by gene. It also has a geographic list of genetic
counselors and information for care-givers. The database has more than
100 condition summaries and 80 gene summaries and new content is being
added continuously.
The Library launched Tox Town late in 2002. Tox Town looks at an
ordinary town and points out many environmental hazards that might
exist there. Users can click on a town location, like the school, and
see a colorful dollhouse-style cutaway view of that building. Toxic
chemicals that might be found in the school are listed, along with
links to selected Internet resources about school environments. There
are similar cutaways for offices, factories, parks, and other
locations. NLM has plans to add new scenes, such as an urban community
and a farming region.
SERVING SPECIAL COMMUNITIES
With all these unique information resources, it becomes more and
more important for the Library to engage in outreach to let citizens
know what is available. The 5,100-member National Network of Libraries
of Medicine is an important partner in these outreach endeavors. Many
of the programs are directed at minority populations. For example,
there are programs to assist in remedying the disparity in health
opportunities experienced by African Americans, Latinos, Native
Americans, senior citizens, and rural populations. A new NLM database
introduced in 2003 has health information aimed at Asian Americans;
2004 will see a similar database with information about the health
concerns of Native Americans.
Under a program with the Historically Black Colleges and
Universities (HBCUs), NLM is helping to train people to use information
resources in dealing with environmental and chemical hazards. The
latest aspect of this outreach effort is NLM's collaboration with the
United Negro College Fund Special Programs Corporation to work with the
HBCUs in the area of consumer health to encourage the use of reliable
electronic health information (such as that provided by the NLM) by the
public.
NLM also has been instrumental in reaching out to other countries
around the world to help improve their access to scientific medical
information. The oldest such program is that involving formal
partnerships with major institutions in 20 countries. The NLM helps
them obtain computerized access to the literature; the countries in
turn help NLM receive the medical literature from that part of the
world. The Library is also a key player in the Multilateral Initiative
on Malaria, the multiagency effort to improve malaria research in
African nations. NLM's role is to establish and maintain the first
malaria research communications network, MIMCOM. There are now 19
research sites in 9 countries participating, with full access to the
Internet.
SCIENCE ADVANCES
Many scientists believe that molecular biology is the primary
driver of medical advances in the 21st century. The rapidly increasing
volume of molecular data and the need to decipher its cryptic and
subtle patterns has created demanding requirements for computerized
databases and analysis tools, special curatorial expertise, and unique
physical facilities. The National Center for Biotechnology Information
is a key player in ensuring that the outpouring of data from molecular
biology laboratories around the world is turned to life-enhancing
purposes. GenBank, as noted above, is growing rapidly with
contributions received from scientists around the world. Scientists
also avail themselves of sophisticated computational tools, such as the
BLAST suite of programs, which lets scientists search enormous
quantities of data for sequence similarities that will identify genes
and genetic features. Another tool, Entrez, allows users to search DNA
sequences and literature information with techniques that are fast and
easy to use. The newest tool is the ``Reference Sequence Collection,''
which provides a centralized, integrated, non-redundant set of
sequences that is integrated with other information for all major
research organisms. Using the Reference Sequence Collection, time once
spent on having to identify, gather, and analyze data can now be spent
effectively on research.
The Center is now also conducting research using the human genome
sequence to begin exploring the history of human populations. NCBI
researchers, working with other collaborators, first assembled a set of
500,000 high-confidence variations and then compared the distribution
of these variations on the genome to that predicted by several models
of population history. They found that the data best fit a model in
which the human population shrank dramatically about 40,000 years ago,
a time when modern humans first appeared in Europe. The model suggests
that the population subsequently grew about 30,000 years ago,
consistent with archaeological evidence of a population expansion
during that period. The results indicate that databases of genetic
variation constructed alongside the human genome project can provide a
unique insight into the history of human populations. This insight may
also explain how these populations may respond differently to selective
pressures such as infectious diseases.
NLM's Lister Hill National Center for Biomedical Communications
sponsors high-technology communications research projects in such areas
as high quality imagery, medical language processing, high-speed access
to biomedical information, developing intelligent database systems,
multimedia visualization, data mining, and machine-assisted indexing.
One prominent area of research has been the Visible Human Project. The
project consists of two enormous (50 gigabytes) data sets, one male and
one female, of anatomical MRI, CT, and photographic cryosection images.
These data sets are available through a free license agreement to 1,800
individuals and institutions in 47 countries where they are being used
in a wide range of educational, diagnostic, treatment planning, virtual
reality, artistic, and industrial applications. An ``Insight Toolkit''
has been developed and makes available a variety of open source image
processing algorithms for computing segmentation and registration of
medical data. The Visible Human Web site is one of the most popular of
all NLM's Web offerings.
NLM's Extramural Programs for more than 20 years has supported the
training of medical informaticians at universities across the nation.
In the early years the program focused on training of informaticians
for clinical care. Today the training programs have added opportunities
for training in bioinformatics, the field of biomedical computing for
the large datasets characteristic of modern research. At present, NLM
provides 18 grants to biomedical informatics training at 26
universities, supporting 250 trainees. NLM also participates in the NIH
Roadmap activities, almost all of which have major emphasis on
biomedical computing. For example, training is an important requirement
of the National Centers for Biomedical Computing, an initiative for
which NLM is one of the key leaders. Training as embedded in Roadmap
activities is expected to become a significant complement to NLM's
traditional support of informatics training.
THE FUTURE
In its role as the world's largest medical library, the NLM will
continue to provide free access to the enormous literature of the
health sciences, including even priceless historical treasures dating
to the 11th century. As to the 21st century, the Library is making
major contributions to the NIH Roadmap and is also applying its
unparalleled collections and talents to ``BIOSHIELD,'' the Department
of Health and Human Services' effort to combat bioterrorism. The
ability to apply medical knowledge to make our citizens healthy and
safe is to repay the investment of the nation in medical research. In
this, the National Library of Medicine can be of great help.
______
Prepared Statement of Dr. Ting-Kai Li
I am pleased to present the President's budget request for the
National Institute on Alcohol Abuse and Alcoholism (NIAAA) for fiscal
year 2005, a sum of $441,911,000, which reflects an increase of
$13,486,000 over the comparable fiscal year 2004 appropriation.
As the recent NIAAA National Epidemiologic Survey on Alcohol and
Related Conditions (NESARC) has shown, most cases of alcoholism are
established by age 25, beginning as early as age 18.\1\ These new
results, which are corroborated by studies not yet published, call for
a major refocusing of research on youth as the most important target
for preventing alcohol abuse and alcoholism on a public-health scale.
We now know that youth and adolescence are the critical window of
opportunity. The earlier one drinks in adolescence, the greater the
likelihood that he or she will develop alcoholism.
---------------------------------------------------------------------------
\1\ NIAAA National Epidemiologic Survey on Alcohol and Related
Conditions, 2003, and unpublished data from the Collaborative Studies
on the Genetics of Alcoholism.
---------------------------------------------------------------------------
The public-health implications of preventing alcoholism before it
becomes established in youth are large, given the magnitude of alcohol
misuse and its consequences. The 2002 report of the World Health
Organization ranks alcohol third as a preventable risk factor for
premature death in developed nations. Only tobacco and cholesterol are
greater risk factors.
In the United States, almost 18 million American adults met the
clinical diagnostic criteria for alcohol abuse or alcohol dependence in
2002.\2\ Annual costs to U.S. society of the consequences of alcohol
misuse are about $185 billion.\3\
---------------------------------------------------------------------------
\2\ Grant BF, Dawson DA, Stinson FS, Chou SP, Dufour MC, Pickering
RP. The 12-month prevalence and trends in DSM-IV alcohol abuse and
dependence: United States, 1991-1992 and 2001-2002. Drug and Alcohol
Dependence, in press, 2004.
\3\ Harwood, H.; Fountain, D.; and Livermore, G. (2000). The
Economic Costs of Alcohol and Drug Abuse in the United States 1992
(updated for 1998). Report prepared for the National Institute on Drug
Abuse and the National Institute on Alcohol Abuse and Alcoholism,
National Institutes of Health, Department of Health and Human Services.
NIH Publication No. 98-4327. Rockville, MD: National Institutes of
Health.
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Heavy alcohol use in the American military is on the rise, with
more than 19 percent of male personnel and more than 5 percent of
female personnel reporting heavy use.\4\ (The Department of Defense
defined heavy drinking as five or more drinks on one occasion, at least
once a week, in its survey). This pattern of drinking is hazardous to
the health and welfare of the individual, the family, and society. In
the general population of the United States, alcohol-related illness
and injury account for at least 8 percent of all emergency-room
visits.\5\
---------------------------------------------------------------------------
\4\ The 2002 Department of Defense Survey of Health Related
Behaviors Among Military Personnel.
\5\ McDonald III AJ, Wang N, Camargo Jr CA. U.S. Emergency
Department Visits for Alcohol-Related Diseases and Injuries Between
1992 and 2000, Archives of Internal Medicine, 2004;164:531-537.
---------------------------------------------------------------------------
ALCOHOL USE BY YOUTH
Alcohol is the primary psychoactive substance of abuse by American
children. As the NIAAA fiscal year 2005 Congressional Budget
Justification notes, 78 percent of 12th graders, 67 percent of 10th
graders, and 47 percent of 8th graders have used alcohol.
The same source of those statistics, the National Institute on Drug
Abuse's Monitoring the Future survey, also indicates that youth who
report having been drunk at least once include 62 percent of 12th
graders, 44 percent of 10th graders, and 21 percent of 8th graders.
Roughly half of those percentages say that they drank heavily five or
more drinks in a row in the past 2 weeks.
The NESARC data show that most cases of addiction, not only to
alcohol, but also to other drugs of abuse, first occur in youth, after
which new cases drop off sharply. The same research shows that, by
comparison, new cases of depression do not follow this trajectory,
instead continuing to rise after adulthood.
REFOCUSING THE RESEARCH
The new finding that youth is the stage of life during which
alcoholism is most likely to begin calls for a shift in the emphasis of
our research. By focusing even more strongly than we currently do on
developing strategies to prevent the onset of alcoholism in this
population, we have the potential to dramatically reduce, overall, the
occurrence of this common disease.
Likewise, shifting the focus of our medication development program
to the early stages of the disease stands to improve the effectiveness
of treatment. As with most diseases, early treatment for alcoholism
could prevent a host of problems, including the medical sequelae of
heavy alcohol use, which are estimated to cost $18.9 billion annually.
Studies show that a combination of factors underlie drinking
behaviors. Environmental factors--family and peers, for example--are
the dominating influences on whether or not an individual first uses
alcohol. Personality and temperament also influence the decision to
begin drinking. These factors have a profound effect on youth.
Whether or not drinking continues also is influenced by
differences, from individual to individual, in the pharmacological
effects (activities of genes, proteins, and metabolic products) that
come into play once drinking has begun. When drinking progresses to
alcoholism, alcohol's pharmacological effects will have become the
dominant influence on drinking behavior.
Identifying the pharmacological effects of alcohol is essential to
our ability to design effective prevention and treatment strategies for
youth. In childhood and adolescence, the pharmacological effects of
alcohol are occurring at a time of rapid structural and physiological
change in the brain. One of the major questions before us is how
alcohol's pharmacological effects work in ways that specifically
promote alcoholism during this vulnerable time of life. Two NIH Roadmap
initiatives will be particularly informative in this regard, as
follows.
The Roadmap Metabolomics Technology Development Initiative will
enhance our ability to identify metabolic processes that contribute to
alcohol dependence (and alcohol-related organ damage). People have
differences in the genes that regulate their cellular mechanisms,
including the enzymes responsible for alcohol metabolism. These
differences result in variations in how people respond to alcohol; for
example, the choice to drink and the amount of alcohol consumed.
Proteins, such as the receptors and transporters for
neurotransmitters, play roles in virtually every step of alcohol's
actions in the brain and other organs. Another Roadmap initiative, the
National Technology Centers for Networks and Pathways, will remove
barriers to defining how these proteins behave in the complex
biological systems in which they interact. Such proteins are potential
targets for medications, but efforts to alter the actions of proteins
with potential medication compounds have thus far met with limited
success in preventing and treating alcohol-use disorders in adults.
This Roadmap initiative will provide much-needed tools that will help
us track the interactions of specific proteins at specific points in
time and cellular space an ability that will enable us to develop more
precise targets for medications to treat the early stages of
alcoholism.
ACTIONS UNDERWAY
Our current research on drinking by youth includes studies of the
neurobiological mechanisms of adolescent alcohol abuse; an initiative
on preventing alcohol-related problems among college students; expanded
testing of preventive interventions, from rural children to children in
urban, diverse neighborhoods; and an initiative that is examining risk
factors and testing community-based, longitudinal prevention programs
among children in rural and small urban areas, in response to fiscal
year 2004 House Appropriations Report language.
Included in NIAAA's fiscal year 2005 Congressional Budget
Justification is an expansion of the latter initiative among youth in
rural and small urban communities, both of whom have high rates of
alcohol use. Both biological and environmental studies, as well as
studies of prevention strategies, will be included. The Substance Abuse
and Mental Health Services Administration, the National Institute on
Drug Abuse, the National Institute of Child Health and Human
Development, the National Institute of Mental Health, and other NIH
Institutes, as well as the Department of Education and other Federal
agencies, will be invited to collaborate in this initiative.
In addition to our research, we conduct outreach programs for
youth. The Leadership to Keep Children Alcohol-Free has recruited 33
Governors' spouses to spearhead a national prevention campaign. The
Task Force on College Drinking has brought together university
presidents and researchers, and is making headway in efforts to reduce
drinking by college students and in evaluating those efforts.
THE LARGER PICTURE
Alcohol abuse and alcoholism often result in behavioral outcomes
such as property damage, legal problems, disrupted family lives, and
derailed academic pursuits and professional careers. But its
consequences also include medical sequelae. With prolonged, heavy use,
it can act as a toxin, damaging virtually any organ in the body. For
example, alcohol is a leading cause of liver cirrhosis and contributes
to some kinds of cancer. Approximately 77 percent of the annual $185
billion cost of alcohol misuse is health-related, generated by medical
consequences and lost productivity associated with illness or death.
Research leading to effective strategies for preventing and
treating alcoholism early in life, when it is most likely to begin, can
help avert many other costly problems. While we will increase our
research on drinking by youth, we will continue our studies of the many
other facets of alcohol use, such as fetal alcohol syndrome, as well as
our research on the apparent protective effect of moderate drinking
against certain chronic diseases.
CONNECTION TO OBESITY
We will also conduct research on alcohol's role in the national
obesity epidemic. In addition to acting as a drug, alcohol is a food--a
highly caloric food. It has more calories per gram than do
carbohydrates or proteins.
In addition, alcohol acts on some of the same neurotransmitter
systems that regulate appetite. Some medications that work to reduce
appetite may also reduce alcohol intake. One of the highest priorities
that NIH lists in its Government Performance and Results Act goals is
human testing of the compound rimonabant for its potential to reduce
alcohol use.
Among the many neurotransmitter receptors that alcohol affects is
the one receptor to which the active ingredient in marijuana binds.
Stimulation of this receptor promotes appetite, and NIAAA animal
studies show that blocking the receptor with rimonabant has the
potential to reduce drinking in humans. NIAAA is preparing a human
trial of rimonabant for treatment of alcoholism. Rimonabant made news
in March of this year, when a French company announced the medication's
effectiveness in reducing both weight and smoking.
The anticonvulsant topiramate also is being tested for its
effectiveness in reducing both obesity and alcohol use, through actions
on another neurotransmitter system. The neurotransmitter gamma-
aminobutyric acid (GABA), among many others, is known to be an
important intermediary of alcohol's actions in the brain.
Obesity and alcohol are linked in yet another way, recent studies
show. The livers of obese rats undergo more cell death and sustain more
injury from heavy, periodic alcohol use than do those of their slimmer
counterparts. In humans, liver damage is one of the most prevalent
medical consequences of chronic drinking.\6\
---------------------------------------------------------------------------
\6\ Carmiel-Haggai M, Cederbaum AI, Nieto N. Binge ethanol exposure
increases liver injury in obese rats. Gastroenterology, 125(6):1818-33.
Dec. 2003.
---------------------------------------------------------------------------
IMPLICATIONS
On a large scale, epidemiology tells scientists where the action
is. That is the case with our new findings on the stage of life when
alcoholism is most likely to develop; that is, by age 25. We are
beginning to take steps to greatly increase our focus on this period--
on how variations in genetic, biological, and environmental factors
unfold to promote establishment of alcoholism during development.
Meanwhile, the NIH Roadmap initiatives on metabolomics and proteomics
are developing tools that can significantly accelerate our research.
______
Prepared Statement of Dr. Lawrence A. Tabak
Mr. Chairman and Members of the Committee: I am pleased to present
the President's budget request for the National Institute of Dental and
Craniofacial Research (NIDCR) for fiscal year 2005. The fiscal year
2005 budget includes $394,080,000, an increase of $11,032,000 over the
fiscal year 2004 level of $383,048,000 comparable for transfers
proposed in the President's Request.
DELIVERING ON THE PROMISE OF BASIC RESEARCH
Although highly technical in nature, basic research provides the
detailed molecular clues that scientists and clinicians can use to
develop new strategies that more effectively prevent or treat disease.
This year, I would like to highlight how NIDCR's investment in the
basic sciences continues to yield important advances in oral and public
health. I also would like to mention how NIDCR stands to benefit from
the recently launched NIH Roadmap which has the potential to catalyze
virtually all areas of oral health research and, most importantly,
hasten the development of novel treatments that could greatly improve
American oral health.
GENE TRANSFER AND THE SALIVARY GLANDS
A prime example of basic research creating new clinical
opportunities is the transfer of replacement genes into the salivary
glands for therapeutic purposes. In the early 1990s, a team of NIDCR
scientists published their initial paper on the technical feasibility
of this approach. Thereafter, they began a unique long-term research
interest in transferring replacement genes into the salivary glands of
persons with Sjogren's syndrome and cancer patients whose salivary
glands were damaged during radiation treatment. The hope was that the
replacement genes would increase the production of saliva and eliminate
the chronic parched sensation that plagues people with dry mouth
conditions.
The NIDCR scientists also began to apply their gene transfer
studies to a third and seemingly less obvious therapeutic area: single-
protein disorders, such as type I diabetes, human growth hormone
deficiency, and erythropoietin-responsive deficiencies. Frequently
overlooked in the medical literature, salivary glands not only release
saliva into the mouth, they routinely secrete digestive enzymes and
other proteins into the circulatory system. As the scientists later
would demonstrate, the salivary glands readily accept gene-carrying
vehicles, or vectors. Thereafter, with minimal coaxing, the salivary
glands act as natural protein factories, dutifully manufacturing the
encoded replacement protein and pumping it at steady levels into the
circulation. The approach has some built in advantages over gene
therapy in other parts of the body, such as the liver. Salivary glands
are easily accessible and any potential adverse effects would be non-
life threatening. Moreover, salivary gland cells are encapsulated to
prevent leakage of the vector into the circulation and to other
tissues.
Recently, the group developed a new version of gene-carrying vector
that entered the salivary glands of mice and produced the human protein
erythropoietin for at least one year, a major step forward in the
research. Just as importantly, the vector--a stripped down,
bioengineered version of the harmless adeno-associated virus--did not
trigger a sustained immune response, a common setback in gene therapy
experiments.
Building on this strong basic research base, NIDCR has developed a
new initiative to evaluate the safety and efficacy of salivary gland
gene transfer techniques in people with systemic single-protein
deficiencies. The initiative will consist of three Phase I/II clinical
trials. The first clinical trial will involve a prototype systemic
single-protein deficiency disorder, adult growth hormone deficiency. As
currently proposed, 21 patients will be enrolled in the study, which
will be completed in four years. If successful, a second clinical trial
will be conducted to treat people with erythropoietin-responsive
deficiencies and ultimately a third clinical trial for those with
Sjogren's syndrome and/or cancer patients with dry mouth.
PERIODONTAL DISEASE AND PRETERM BIRTH
Another outstanding example of basic research creating new clinical
opportunities is in the area of preterm pregnancy. In the United
States, about one in eight babies is born prematurely,\1\ which is
defined as a birth that occurs three or more weeks earlier than the
expected due date. As all too many parents have tragically experienced,
extremely preterm babies can be so small and underdeveloped that they
must remain hospitalized for months and, if they survive, spend years
battling chronic health problems.
---------------------------------------------------------------------------
\1\ March of Dimes Defects Foundation. http://
peristats.modimes.org. Access on March 15, 2003.
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This serious and common problem has spurred scientists to identify
``risk factors'' associated with premature births. These risk factors--
which now include smoking, low-income status, hypertension, diabetes,
alcohol use, genitourinary tract infections--allow doctors to identify
women who are more likely to deliver prematurely and thereby tailor
their prenatal care to control or eliminate the risk factors.
However, the list of risk factors remains a work in progress. An
estimated one in four preterm births occur without any known
explanation, and that has left scientists searching for additional
susceptibility factors to help more mothers and reduce the estimated
$13.6 billion per year spent in the United States on hospital stays for
infants with a diagnosis of prematurity.\2\
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\2\ March of Dimes, PeriStats.
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In the mid 1980s, scientists began to suspect that periodontal
disease might be one of these elusive risk factors. These NIDCR
grantees and colleagues monitored women with more serious periodontal
disease and found they were more likely to deliver early than those
with mild or non-existent disease. They also have developed a plausible
biological explanation to explain the possible association. Based on
animal studies, the scientists hypothesized that certain bacteria from
severe periodontal infections, most notably Porphyroma gingivalis,
enter the bloodstream and eventually circulate to the womb. There, the
oral pathogens colonize and irritate the uterine wall. This causes
inflammation of the uterus and a rise in prostaglandins and other
infection-signaling chemicals, which can induce early contractions and
trigger premature labor.
Left unanswered is whether treating women for periodontal disease
during pregnancy will help them give birth to full term babies. The
NIDCR recently launched two large randomized clinical trials to answer
this important public health question. These national studies, which
merge the disciplines of dentistry and obstetrics, will involve over
2,600 women of various racial, ethnic, and economic backgrounds. What
is unique about these clinical trials is there will be a yes-or-no
outcome for each woman within 37 to 40 weeks, or the completion of the
pregnancy. Women will not need to be tracked at great expense for 10 or
20 years to get the final answer, as is often the case in clinical
research. Once all the data are compiled and analyzed, which could take
an estimated five years to assemble and analyze, researchers anticipate
that they will have sufficient clinical data to offer sound scientific
advice one way or the other on this critical public health issue.
PAIN RESEARCH
In another example of the potential payoff from basic research,
scientists are mapping in greater detail the multiple routes, or
pathways, that sensory signals travel en route to the spinal cord and
brain. This work has resulted in several new leads in how to more
effectively manage pain. One of the most promising new leads stems from
work conducted at the NIDCR. Our scientists found that an ultrapotent
compound selectively eliminated an entire class of pain-sensing neurons
from the peripheral nervous system of a living organism. The compound,
called resiniferatoxin (RTX), killed the neurons, blocking inflammatory
pain, thermal pain sensation, and reducing hypersensitivity to pain.
Importantly, the animals maintained their ability to sense pain, in
this case from a pinch, and they remained well coordinated, an
indication that RTX did not affect sensory nerves in the muscles and
joints. Since these initial reports, the investigators have assembled
additional preclinical data and are moving rapidly toward evaluating
RTX in human clinical trials.
In order to seed additional discoveries in pain research and to
help more Americans effectively manage pain, the NIDCR will begin an
initiative to define the proteins and protein networks involved in
processing pain-signal information in the orofacial region. This
initiative encourages interdisciplinary studies that employ genomic and
proteomic approaches, imaging technology, and computational biology to
clarify the molecular events involved in chronic orofacial pain
disorders.
PUTTING RESEARCH INTO PRACTICE
To achieve our goal of improved oral health for all people, NIDCR
must ensure that research advances are translated and adopted into
clinical practice. Many of the unique questions faced by dental health
professionals on a daily basis are most appropriately addressed in
dental practice settings, among unselected patient populations.
Practice-based research networks can generate important and timely
information to guide the delivery of health care and improve patient
outcomes. The NIDCR will launch an initiative to create dental
Practice-Based Research Networks (PBRNs) to conduct clinical research.
In time, linking the oral health practice-based research networks with
existing medical networks will provide additional patients,
professional expertise, and integration of resources for conducting
research across a broad spectrum of health care specialties. By
connecting practitioners with experienced clinical investigators, PBRNs
will enhance clinical research supported by the NIDCR and produce
findings that are immediately relevant to practitioners and their
patients. The networks can support a variety of clinical studies with
clear and easily defined outcome measures, and they typically draw on
the experience and insight of practicing clinicians to help identify
and frame the questions. Because research is conducted in the real-
world environment of dental practice, the results are more likely to be
readily adopted by practitioners.
NIH ROADMAP
The NIH Roadmap provides several additional opportunities to the
oral-health research community. For example the goals of the initiative
Building Blocks, Biological Pathways and Networks--are closely linked
to NIDCR's molecular anatomy efforts to identify the full complement of
genes, proteins and protein networks that are expressed in both oral
cancer and periodontal disease. Advances in proteomic analysis
platforms will be crucial for NIDCR to achieve its goal of defining the
salivary proteome--a critical step in the Institute's long-term goal to
exploit the salivary secretions for diagnostic purposes. The Molecular
Libraries and Molecular Imaging initiative holds great promise for
accelerating NIDCR's progress in defining the molecular pathways of
pain reception and in elucidating new therapeutic targets to manage
chronic pain. In addition, the initiative Research Teams of the Future
will enable NIDCR's ongoing inter- and multi-disciplinary efforts to
further expand and develop new ways to approach research questions.
Finally, the integration of dentists into the new clinical research
infrastructure that will be created by the Roadmap is key given that
overall health and oral health are interrelated and that certain
systemic conditions such as diabetes, Sjogren's syndrome, HIV/AIDS and
osteoporosis have important oral symptoms, manifestations or
complications.
NIDCR envisions a clear path ahead for oral and craniofacial
research. Many exciting new leads that have been reported in recent
years makes it easy to imagine that the next wave of research advances
will have a more profound and far reaching effect on oral health than
ever before.
Senator Specter. Thank you very much, Dr. Zerhouni.
We have been joined by two members of the Appropriations
Committee. Let me turn first to the distinguished chairman of
the full committee, Senator Stevens.
Senator Stevens. Well, Mr. Chairman, I am late. So I will
just ask to put my statement in the record. I do greet our
friends at the table and look forward to the comments and
questions.
Senator Specter. Without objection, the statement will be
made a part of the record.
[The statement follows:]
Prepared Statement of Senator Ted Stevens
Thank you Mr. Chairman. It's a pleasure to welcome Dr. Zerhouni and
his distinguished colleagues who head up the Institutes at NIH here
today.
I'd also like to thank Dr. Andy von Eschenbach. Andy, I understand
from my good friend Dr. Mike Phelps that you gave an excellent speech
this past Sunday to the Academy of Molecular Imaging meeting in
Orlando. As you know, PET and Molecular Imaging are special interests
of mine.
I must be brief since I have three other hearings where I must make
an appearance. However, I want to commend Dr. Zerhouni for his efforts
to develop the ``Roadmap'' initiative.
That initiative aims to focus NIH's resources on several broad
categories of medical research and to bring together different
disciplines to make real, rapid and visible progress to determine the
true basis of many diseases and then to treat them. The Roadmap, with
its focus in the Director's office is important because no single NIH
Institute can address these problems alone.
I'm particularly pleased that you have chosen to focus early
efforts of the Roadmap on the integration of nanotechnology, systems
biology, and molecular imaging. By combining these three disciplines we
hope to discover the molecular basis of diseases like cancers and then
to develop targeted molecular therapies to arrest the progress of the
disease and cure it.
In the fiscal year 2004 appropriations legislation I sponsored an
amendment to give the Director of NIH new authority to put together
innovative collaborative approaches to medical research to help speed
up the process. I hope that you, Dr. Zerhouni, will use that authority
to take bold and visionary steps to help us find these cures.
I've been a longtime supporter of large increases in funding for
medical research. I continue that support, but I must warn you that it
will be more and more difficult to sustain increases for medical
research unless you do pursue bold new approaches such as nanosystems
biology that have the potential to show real results that the American
taxpayer can see. We must begin to show a return on our investment in
order to continue it.
Once again, I commend Dr. Zerhouni and the directors of the NIH
Institutes for their leadership and efforts on behalf of all people.
Senator Specter. Senator Cochran, do you have an opening
statement?
OPENING STATEMENT OF SENATOR THAD COCHRAN
Senator Cochran. Mr. Chairman, thank you very much. I have
submitted a statement as well and hope it will be included in
the record.
I want to commend the Director and his associates who are
here today for the fine work that you are doing. I am
particularly impressed with the work in health disparities and
some of the research that is being undertaken now and funded by
the National Institutes of Health.
PREPARED STATEMENT
I notice an increase in the budget request for the National
Center for Minority Health and Health Disparities. I think that
is the entity that is supporting the Jackson Heart Study in my
State where very meaningful work is being done in conjunction
with the University of Mississippi Medical Center and Jackson
State University and other educational institutions in our
State to try to get at the bottom of some of the questions of
why there is such a disparity in some kinds of heart diseases.
This is being done in conjunction with the National Heart,
Lung, and Blood Institute as well. But I think the need for
more research, conducted in the places where we are
experiencing health disparities or high incidences of chronic
diseases, is something that is overdue, and I congratulate you
for taking this initiative.
[The statement follows:]
Prepared Statement of Senator Thad Cochran
Dr. Zerhouni, thank you for joining us today to discuss the budget
for the National Institutes of Health. We have had great success in
increasing NIH funding. It is my hope that we continue to support high
quality research, and focus this research on the most pressing health
issues of our country. Our goal should be to make sure NIH research
benefits all Americans.
I know you are familiar with the Jackson Heart Study, which looks
at the reasons why African-Americans suffer disproportionately from
heart disease. I hope the NIH will continue to take an active role in
making sure research like this reaches underserved areas of our
country. This relatively small investment has made a tremendous impact
on my state. I am encouraged by the progress made by institutes, like
the National Center for Minority Health and Health Disparities. I am
pleased to support NIH in these efforts.
Senator Specter. Thank you, Senator Cochran.
We will now proceed with 5-minute rounds of questioning, as
is the custom of the subcommittee.
FISCAL YEAR 2005 BUDGET REQUEST
Dr. Zerhouni, your proposed budget will permit grant
increases by only 1.3 percent instead of the inflationary
increase of 3.5 percent. If NIH applied its usual policy of
providing an average grant increase equal to the rate of
inflation, it is my understanding that about 640 fewer
competing grants would be funded than in 2004.
First of all, is that accurate?
Dr. Zerhouni. That is accurate, Senator.
Senator Specter. After the increases which we have provided
over the last 5 years, do you think the proposed budget is
sufficient to maintain the momentum and bring discoveries from
the laboratory to the doctor's office?
A subset of that is, how much additional funding would be
required to restore the usual NIH average cost policy, assuming
the same number of grants which are now in the budget?
Dr. Zerhouni. Ideally, Mr. Chairman, you would like to be
sure not to fall behind inflation. However, this year, because
of the very difficult budget environment, we had to make some
difficult choices. We elected to maintain the number of grants
to be able to provide as many scientists the opportunity to
succeed in applying and made some sacrifices on the cost
increases.
If we had $220 million more--the number is $220 million--we
could satisfy both conditions: have enough grants and
inflationary increases.
Senator Specter. If the Congress is willing to appropriate
the additional $1.3 billion, what new research initiatives
would NIH be able to conduct with these additional funds?
Dr. Zerhouni. As you know, because of the doubling and the
opportunities offered by the doubling, many of our institutes,
if not all of them, have opportunities in translation in
clinical research. This is the area of research generally that
is difficult to undertake in a budget that is the budget that
we are requesting.
So when you look at the priorities that we would have to
fulfill, if we had more resources, the first one would be to
keep up with inflation. The second would be to continue our
analysis and the framework for the Roadmap for medical
research, accelerate that. We have some programs like the
extramural construction programs, the IDeA program, that we
would like to enhance over time, including training stipends.
But the most important report from all the institutes is that
there are some clinical trials in translational research that
will have to be slowed down.
Senator Specter. Well, I would like to have a more detailed
answer for the record on what the impact will be on the
administration's request contrasted with what the impact would
be on an additional $1.3 billion. So we have specific
information as to how many grants there would be, what will
happen to the clinical programs.
Let me turn now to the issue of stem cell research. You and
I have discussed this at some length and the President made his
famous statement back on August 9th of 2001 about certain stem
cell lines being added. Some of those stem cell lines are
contaminated with mouse feeder cells. Some of those stem cell
lines are owned other places. We see Harvard with a $100
million allocation, which is wonderful but nothing compared to
the $28 billion you have. We see South Korea taking the lead.
We see scientists leaving the United States because ideology is
conflicting with medical research.
[The information follows:]
Research That NIH Could Fund With an Additional $1.3 Billion
The fiscal year 2005 President's Budget requests an additional $764
million for NIH, a significant increase to the program level given the
competing priorities within the Federal budget. An additional $1.3
billion over the request would provide $30.057 billion, an increase of
7.2 percent over fiscal year 2004. With this additional funding, NIH
would fund a larger share of the great research ideas that scientists
submit to us. We would be able to fund about 700 more research project
grants, increasing chances of a scientist's application being funded
and increasing the currently expected ``success rate'' from the 27
percent in the President's Budget to 29 percent. Additional priorities
would include:
--Accelerating implementation of Roadmap initiatives;
--Implementing an interdisciplinary approach to neuroscience research
by completing the phase 2 of the Porter Neurosciences Building;
--Providing average cost increases equal to biomedical inflation and
finance the committed levels for competing continuation grants;
--Increasing support for research training awards; and
--Increasing the amounts NIH pays on career awards.
Examples of the new research initiatives and significant expansions
of ongoing programs that NIH would conduct with these additional funds
follow:
TRANSDISCIPLINARY RESEARCH ON ENERGETICS AND CANCER (TREC) (NCI)
--Novel initiative involving scientists from multiple disciplines and
encompassing projects spanning the biology and genetics of
energy balance to behavioral, sociocultural, and environmental
influences upon nutrition, physical activity, weight, energy
balance and energetics.
--The TREC Centers would foster collaboration among transdisciplinary
teams of scientists with the goal of accelerating progress
towards reducing cancer incidence, morbidity and mortality
associated with obesity, low levels of physical activity and
poor diet.
--Centers would also provide training opportunities for new and
established scientists who can carry out integrative research
on energetics, energy balance and its consequences.
CANCER BIOMEDICAL INFORMATICS GRID (CABIG) (NCI)
--Cancer research platform with common standards to expedite progress
by creating a network that links organizations, institutions,
and individuals to enable the sharing of cancer research
infrastructure, data, and tools.
--All cancer researchers would have access to a common research
infrastructure that creates a plethora of opportunities to not
only make important new findings but to do so more quickly and
efficiently than ever before.
--This new system would offer a library of tools and resources--from
clinical trial management systems to tissue bank and pathology
tools--that are all built to common standards and are
interoperable with other existing systems.
--Study population data would be far more robust and researchers will
be able to mine data in a way that simply isn't possible at the
moment.
--Joins the various fields of cancer research--from etiologic
research to prevention, early detection and treatment.
UNDERSTUDIED CANCERS OF HIGH LETHALITY (NCI)
--A key element to the elimination of death from cancer by 2015 would
be to focus on malignancies which are highly fatal, such as
pancreatic, esophageal, and liver cancers.
--When these cancers are found, relatively little prolonging of life
or quality of life follows.
--Understanding gene-environment interactions is important in
learning who is at elevated risk, and how that risk is
regulated.
--Discoveries in these areas would lead to more accurate and cost-
effective public health interventions aimed at eliminating
mortality.
PATIENT NAVIGATION RESEARCH PROGRAM: ELIMINATING BARRIERS TO TIMELY
DELIVERY OF CANCER DIAGNOSIS AND TREATMENT SERVICES (NCI)
--A major disconnect or gap exists between cancer Discovery and
Development research and Delivery for many Americans. Discovery
and Development research results in beneficial procedures for
cancer prevention, early detection, diagnosis, and treatment
that are intended for all Americans. Health disparities arise
when the Delivery system does not provide access to timely,
standard cancer care to everyone in the nation. NCI has
established the goal of eliminating suffering and death due to
cancer by 2015.
--The NCI is challenging principal investigators to develop effective
patient navigation interventions. These interventions would
address access barriers to quality, standard cancer care. The
purpose of the Patient Navigation Research Program (PNRP) would
be to develop interventions to reduce the time to delivery of
standard cancer care services after identifying a cancer-
related abnormal finding.
--The patient navigator could assist patients and their families
through the cancer care continuum.
--The research hypotheses are that navigated patients would: (1)
receive timelier, definitive diagnosis following screening and
abnormal finding; (2) receive more timely treatment following
positive diagnosis; (3) improve their satisfaction with the
health care system experience.
STUDY TO IDENTIFY RISK FACTORS FOR CORONARY HEART DISEASE (CHD) IN
HISPANIC POPULATIONS (NHLBI)
--The nation's largest minority group.
--Involve four community-based cohorts of adults, one each of
majority Cuban, Puerto Rican, Mexican American, and Central
American origin.
--Examine the role of acculturation in the development of risk
factors and determine if any play a uniquely harmful role in
the development of CHD in Hispanics.
--Include a closely integrated community and professional education
component to return the benefits of research results to the
participating communities.
FIVE-YEAR RANDOMIZED CLINICAL TRIAL OF CHRONIC OXYGEN USE IN MODERATE
TO SEVERE CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) PATIENTS (NHLBI)
--COPD is the fourth most common cause of death in the United States.
--Oxygen therapy is known to extend the life of patients with severe
COPD and hypoxemia.
--Billions of dollars are spent in the United States each year to
provide oxygen for patients with moderate or severe COPD
without good evidence as to who benefits.
--The trial would determine the effects of oxygen therapy on life
expectancy, hospitalization rates, independent living, and
quality of life.
MULTI-CENTER CLINICAL TRIAL TO EVALUATE NEW TREATMENT APPROACHES FOR
SARCOIDOSIS (NHLBI)
--Sacroidosis is a multisystem disease that usually affects the
lungs, and is more common in black Americans.
--Current treatment, which is based mainly on corticosteroids and
cytotoxic agents, is non-specific and has many dangerous side
effects.
--An NHLBI Sarcoidosis Research Working Group and several patient
advocacy groups recommended support for a trial to test new
agents for sarcoidosis.
IDENTIFY AND TEST APPROACHES TO REDUCING CARDIOVASCULAR DISEASE THAT
ARE SPECIFIC TO AMERICAN INDIAN AND ALASKA NATIVE POPULATIONS (NHLBI)
--Such an initiative would test approaches to reducing cardiovascular
disease (CVD) risk factors in American Indian/Alaska Native
(AI/AN) populations that can be incorporated into clinical
programs of community health care systems or delivered through
other public health approaches in native communities.
--Many AI/AN communities bear a heavy burden of CVD and modifiable
CVD risk factors.
--AI/AN communities are concerned that few intervention studies have
been launched to test possible solutions.
PRACTICE BASED RESEARCH NETWORKS OF DENTAL SPECIALISTS (NIDCR)
--NIDCR's Practice Based Research Networks (PBRN) initiative would
otherwise be limited to networks of general dental
practitioners.
--Networks provide an infrastructure for conducting multiple,
collaborative clinical trials and observational studies
relating to dental practice and oral health care.
--Linkage of the oral health PBRNs with existing medical PBRNs would
provide additional patients, professional expertise, and
integration of resources for conducting clinical research
across a broad spectrum of health care specialties.
REGENERATIVE DENTAL MEDICINE (NIDCR)
--Diseases and injuries that damage orofacial tissues have a serious
impact on quality of life.
--Human stem cells would be utilized in combination with new bio-
inspired materials to regenerate the complex structures of the
orofacial system.
--Researchers would develop and test a number of stem cells and
biomaterial structures that mimic the multi-dimensional
architecture/function of tooth structures.
PROSPECTIVE STUDIES ON CRANIOFACIAL PAIN & DYSFUNCTION (NIDCR)
--Participants enrolled in this study would be followed over time to
identify risk factors associated with or predictive of the
onset of craniofacial pain and dysfunction.
--Temporomandibular joint (TMJ) dysfunction is a condition of
particular interest.
CLINICAL RESEARCH TRAINING (NIDCR)
--In the ``post-genomic era,'' translational and clinical research
plays an important role in bringing laboratory observations
into the clinical setting.
--NIDCR's new program announcement would foster clinical research
training in multidisciplinary research settings for all members
of the clinical research team.
FULL-SCALE CLINICAL TRIAL OF PRIMARY INTERVENTIONS TO PREVENT OR DELAY
TYPE 2 DIABETES IN CHILDREN AND ADOLESCENTS (NIDDK)
--Cases of type 2 diabetes are increasing in the pediatric
population, especially among adolescents and in certain
minority groups.
--A school-based intervention approach may be an effective way to
prevent risk factors for type 2 diabetes in children and
adolescents.
--Pilot studies for a multi-site, multi-component, school-based
intervention trial employing both environmental and behavioral
changes are under way; could launch the trial in fiscal year
2005.
IMPROVE CLINICAL TRIALS FOR TREATMENT OF INFLAMMATORY BOWEL DISEASE
(IBD) (NIDDK)
--The conduct of new clinical trials in IBD is hampered by the
current need to rely on indirect diagnostic tests and
nonspecific clinical features.
--The conduct of clinical trials and development of safer, more
effective treatments would be accelerated by research in
proteomics, to discover new biomarkers, and in molecular
imaging, to discover new non-invasive diagnostic imaging tests.
STUDY THE ROLE OF THE INTRAUTERINE AND POSTNATAL ENVIRONMENTS IN THE
DEVELOPMENT OF OBESITY (NIDDK)
--A better understanding of aspects of the intrauterine environment
and a mother's medical status that contribute to future
overweight and obesity in offspring could lead to more
effective interventions before, during, or shortly after
pregnancy.
--Strategies to prevent or treat obesity could also greatly benefit
from research on the impact of diet and other environmental
factors on the early development of brain pathways regulating
calorie intake and energy expenditure, and the permanence of
these effects in adulthood.
--Tools are available to conduct these studies in appropriate animal
models, including primates.
EXPAND FEASIBILITY TRIAL OF DAILY DIALYSIS TO DETERMINE EFFECTS OF NEW,
MORE INTENSIVE DIALYSIS MODALITIES ON MORTALITY AND CARDIOVASCULAR
DISEASE (NIDDK)
--Clinical studies are needed to determine whether life expectancy of
persons with end-stage renal disease (ESRD), or chronic kidney
failure, can be improved by modifying standard dialysis
regimens.
--Clinical centers have been established to test the feasibility of a
randomized clinical trial of more frequent dialysis.
--The current frequent dialysis trial is limited by size and design
to measuring intermediate outcomes, such as blood pressure,
anemia, and quality-of-life.
--An expansion of the trial could enable assessment of the effect(s)
of any change in dialysis regimen on hospitalization rate and
mortality, and on cardiovascular events--e.g., stroke,
myocardial infarction and heart failure--which often complicate
ESRD.
INITIATE THE VERY LARGE PHASE III CLINICAL TRIALS FOR PARKINSON'S
DISEASE (NINDS)
--Necessary to adequately test one or more of the neuroprotective
drugs for Parkinson's disease (minocycline, creatine, coenzyme
Q10 and GPI-1485) that are being tested in pilot trials.
CONDUCT A PHASE III CLINICAL TRIAL OF CEPHALOSPORIN FOR THE TREATMENT
OF ALS (LOU GEHRIG'S DISEASE) (NINDS)
--A screen of 1,040 drugs for potential use against neurodegenerative
diseases revealed one that may be particularly helpful for
ALS--the antibiotic cephalosporin.
LAUNCH CHEMICAL COUNTERTERRORISM RESEARCH TO COMBAT NERVE AGENTS
(NINDS)
--A number of chemical agents and toxins that have served or could
serve as terrorist weapons that target the nervous system.
--Research initiatives would focus on ameliorating the acute
neurologic responses to these chemical weapons as well as
alleviating any chronic neurodegenerative effects.
EXPAND THE SPECIALIZED PROGRAMS OF TRANSLATIONAL RESEARCH IN ACUTE
STROKE (SPOTRIAS) (NINDS)
--From four to eight centers.
--Would accelerate translation of basic research findings into
clinical practice in acute ischemic and hemorrhagic stroke.
INITIATIVE FOR PANDEMIC INFLUENZA (NIAID)
--Accelerate the development of next generation influenza antiviral
drugs and the production and clinical testing of up to four
pilot lots of candidate vaccines by up to one year or more.
--Influenza routinely causes 36,000 deaths per year in the United
States; however, the ability of flu viruses to occasionally
jump from animals to humans poses an imminent threat of a
pandemic affecting millions of people--over 20 million people
worldwide is estimated to have died during the flu pandemic of
1918.
--Research would also expand surveillance of emerging flu strains in
Asian animals to support development of new vaccines against
influenza strains with pandemic potential.
CLINICAL TRIALS OF HIV/AIDS VACCINE CANDIDATES (NIAID)
--Expand clinical trials to accelerate by one or more years clinical
evaluation of six promising HIV vaccine candidates.
--Forty million people were estimated to have HIV/AIDS as of December
2003, with five million new infections occurring in 2003.
Another three million people died of the AIDS pandemic in 2003,
including 500,000 children, with a total of 70 million people
projected to die of the disease by 2020 if the current trends
continue.
--As with other pandemic infectious diseases, a key component to
preventing the spread of HIV/AIDS, and to mitigating the long-
range impact of the AIDS pandemic, is the development of an
effective HIV/AIDS vaccine. Critical challenges to developing
an effective vaccine include the need to clinically evaluate a
large number of promising HIV vaccine candidates in humans as
rapidly as possible to determine the toxicity and effectiveness
of the vaccine candidates. Factors contributing to the need to
clinically evaluate a large number of the most promising
vaccine candidates include the multitude of different HIV/AID
virus strains in existence and the frequency at which the virus
mutates and the fact that the virus infects and destroys the
immune system.
CLINICAL TRIALS IN ORGAN TRANSPLANTATION (NIAID)
--Expand and accelerate clinical trials to develop therapeutic
strategies to reduce the immune-mediated morbidity and
mortality of organ transplantation.
--Over 25,000 people receive organ transplants each year. Although
the one-year survival for single-organ transplantation has
improved over the last 15 years to a level approaching or
exceeding 90 percent, there has been little success in
reversing the decline in long-term graft-vs-host disease and
patient survival (13 percent to 55 percent at 10 years,
dependant upon organ).
--Studies would support both children and adults and will address the
barriers to short- and long-term success of transplant
procedures, including incompatibility between donor and
recipient, acute and chronic rejection, and complications of
long-term pharmacologic immune suppression.
CLINICAL TRIALS OF TOPICAL MICROBICIDES (NIAID)
--Expand existing support of clinical trials to accelerate the
clinical evaluation of four promising microbicide candidates
that have unique mechanisms of action to potentially protect
against sexually transmitted diseases (STD), including HIV/
AIDS.
--Topical microbicides are creams, gels or foams that can be applied
to the vagina or rectum and prevent STD-causing microbes,
including HIV, from invading the host. Pharmaceutical companies
have been reluctant to invest in research on microbicides
primarily because not enough data has been gathered through
large clinical studies in humans to provide a ``proof of
concept'' of any microbicide product.
--A partially effective microbicide could avert more than 2 million
HIV infections over a 3-year span; also, microbicides could
play a critical role in reducing STD transmission from mother
to infant during childbirth.
determine three-dimensional structures of proteins (nigms)
--Partner with other Institutes.
--Includes those related to cancer and emerging infectious diseases.
--Would be useful for the design of new antibiotics or anti-cancer
agents.
RESEARCH RELATED TO DETERMINING WHY DIFFERENT INDIVIDUALS RESPOND
DIFFERENTLY UPON TREATMENT WITH THE SAME DRUGS (NIGMS)
--Would help physicians customize treatment to individual patients
and may guide the development of new drugs that are more
predictively effective in most people.
development of tools for investigating model organisms (nigms)
--Model organisms such as fruit flies, mice, and roundworms have
provided great insights into fundamental biological mechanisms
and into human disease.
INNOVATIVE METHODS OF NEWBORN SCREENING (NICHD)
--While ensuring protection of privacy and providing ethical
safeguards, the NIH could proceed with efforts to identify, at
birth, hundreds of genetic defects associated with mental
retardation, primary immunodeficiency diseases, and other
potentially disabling and fatal conditions.
--Technologies generated by the Human Genome Project are available to
screen for hundreds of genetic diseases in newborns.
--A database in rare genetic diseases could be developed to enable
scientists to identify unrecognized genetic defects in
newborns, to study currently untreatable disorders, and to
develop new therapeutics.
--New screening techniques could allow clinical and preventive
interventions for currently treatable genetic disorders, such
as Severe Combined Immunodeficiency Disease (SCID), in time to
prevent or mitigate risks of early death or life-long
disability.
GENOMIC AND PROTEOMIC RESOURCES FOR PREMATURE BIRTH (NICHD)
--The NIH could establish a major consortium to create high-quality
data on human gene and protein expression, and to make this
information available on a publicly-accessible database that
will be dedicated to prematurity research. Investigators could
mine the database to advance their own research into the causes
of and ways to prevent premature birth.
--Premature birth causes almost 70 percent of neonatal deaths and
reducing prematurity would reduce wide racial disparities in
infant mortality.
--The depth and accessibility of the new genomic and proteomic
database could enable scientists to discover biomarkers for
premature birth and ultimately to develop early diagnostic and
effective treatment interventions.
RESEARCH BASE TO ASSESS EARLY CHILDHOOD LEARNING AND SCHOOL READINESS
(NICHD)
--The NIH could develop, refine, validate, and scale-up tests to
assess how well preschool programs help young children--
especially those at risk of school failure--to achieve ``school
readiness,'' cognitively, socially, and behaviorally.
--Significant academic, public, and political attention is focused on
the educational achievement of all children, beginning with
preschoolers, with certain federal funds tied to school
systems' performance.
--Preschool programs need scientifically-based tests to measure
accurately how well they prepare young children for later
school success. The programs especially need tests to measure
their performance with non-English speaking, ethnically
diverse, and educationally at-risk preschoolers. For the most
part, such tests do not exist, leaving preschool programs
unable to measure their performance for purposes of federal
funding.
--The NIH is the primary research agency with the basic and applied
scientific expertise to produce these tests, which are now
lacking.
THE NATIONAL CHILDREN'S STUDY (NICHD)
--The first two vanguard centers could be established for this
ground-breaking, congressionally-authorized, longitudinal study
of children's health and development. (There would be
significantly larger out-year costs.)
--Extensive planning and selected feasibility studies enable vanguard
centers, for this large and complex research effort, to
investigate how environmental factors, broadly defined, may
influence children's health and development.
--Primary care pediatric practices and other types of clinical sites
could become vanguard sites.
new interventions to improve pregnancy outcomes (nichd)
--The NIH could proceed with clinical trials and related studies to
prevent preterm births and improve neonatal outcomes.
--An NIH research network recently discovered the first effective
intervention--progesterone treatment of high-risk women during
pregnancy--to prevent recurrent preterm birth. The new
treatment cannot be approved by the FDA until researchers study
children of mothers who received the experimental treatment to
detect any later-emerging adverse effect in the children.
--A clinical trial is needed to affirm preliminary findings that a
nutritional supplement during pregnancy (an Omega-3 (n-3)
polyunsaturated fatty acid) is particularly efficacious in
preventing recurrent preterm birth in African American women,
for whom the experimental progesterone treatment was less
effective.
--A clinical trial is needed to affirm preliminary findings that a
single, simple injection of tin mesoporphyrin can successfully
prevent complications of hyperbilirubinemia that can result in
severe, life-long disabilities. If not diagnosed and treated,
hyperbilirubinemia can lead to jaundice, brain injury and
kernicterus (a condition of severe neural symptoms, associated
with high levels of bilirubin in the blood).
clinical trial for the treatment of inflammatory eye disease (nei)
--Would be able to begin a clinical trial to evaluate a treatment for
uveitis that will greatly enhance patients' quality of life.
--Uveitis is a group of ocular inflammatory disorders that represent
a major cause of vision loss and blindness in the United
States.
--This new monoclonal antibody therapy could mean fewer side effects
than current therapies that require systemic, immuno-
suppressive drugs, leading to an improved quality of life.
CLINICAL TRIALS NETWORK FOR THE TREATMENT OF AGE RELATED MACULAR
DEGENERATION (AMD) (NEI)
--Could launch a clinical trials network to test promising new
therapies for age-related macular degeneration.
--A clinical trials network is needed to test a variety of new
treatment approaches targeting the full range of disease forms
and levels of severity of age-related macular degeneration.
--Age-related macular degeneration is the leading cause of vision
loss among Americans over 65 years of age, the fastest growing
segment of the U.S. population.
ROBUST PROGRAM TO EVALUATE THE TOXICOLOGY OF NANOSCALE MATERIALS
(NIEHS)
--Nanoscale materials are already appearing in commerce as industrial
and consumer products and as novel drug delivery formulations.
Commercial applications and resultant opportunities for human
exposure may differ substantially for nanoscale vs. ``bulk''
materials.
--Currently there is very little research focus on the toxicology of
manufactured nanomaterials. There are indications in the
literature that manufactured nanomaterials may distribute in
the body in unpredictable ways and that certain nanoparticles
have been observed to preferentially accumulate in particular
organelles.
--The NTP/NIEHS research program would evaluate the toxicological
properties of major nanomaterials classes which represent a
cross-section of composition, size, surface coatings, and
physico-chemical properties, and use these as model systems to
investigate fundamental questions concerning if and how
nanomaterials can interact with biological systems.
USE OF METABOLOMICS TECHNOLOGIES FOR PREDICTING TOXICOLOGICAL RESPONSES
(NIEHS)
--Assessment of exposure and of risks from exposure could be greatly
improved by using metabolic indicators such as changes in gene,
protein or metabolite expression.
--Research supported by this initiative would focus on the
application of metabolomics technologies to identify predictive
markers of exposure, toxicity and disease in animal and human
populations; link metabolic profiles with biological pathways
and mechanisms of environmentally-related exposures and
diseases; and develop computational and modeling approaches for
assessment and integration of metabolomics data in predictive
toxicology research.
--This program would be a critically important application of the
basic methodology development work being undertaken as part of
the NIH Roadmap initiative on Metabolomics Technology
Development.
PREVENTION TRIALS TO ASSESS THE POTENTIAL ABILITY OF NON-STEROIDAL
ANTI-INFLAMMATORY DRUGS AND A COMBINATION OF ANTI-OXIDANT VITAMINS
(NIA)
--Prevent Alzheimer's disease and age-associated cognitive decline.
development of a clinical trials consortium (nia)
--Test testosterone therapy for older men with low testosterone
levels who experience weakness, frailty, or a specific
disability that may be related to low testosterone.
NEW INTERVENTIONS FOR PREVENTION AND CONTROL OF HEART FAILURE IN
PERSONS AGED 65 AND OLDER (NIA)
--Fully develop and validate new interventions through clinical
trials.
MULTIDISCIPLINARY IMAGING RESEARCH PARTNERSHIPS FOR ADDRESSING
IMPORTANT BIOLOGICAL OR MEDICAL RESEARCH PROBLEMS OF SKELETAL MUSCLE
AND ASSOCIATED SOFT TISSUE (NIAMS)
--Improved imaging techniques provide a non-invasive way to monitor
changes in muscle (including muscular dystrophy and other
muscle diseases) and soft tissue.
--Multidisciplinary imaging research partnerships would stimulate the
development of novel imaging technologies that will help us
understand the genetic and molecular bases of musculoskeletal
soft tissue function, disease, and injury processes.
--Improved visualization of skeletal muscle and associated soft
tissue would enable researchers to more accurately measure
change during treatment or recovery from injury.
PURSUE THE RESEARCH NEEDS AND OPPORTUNITIES IDENTIFIED AT THE RECENT
NIH CONSENSUS DEVELOPMENT CONFERENCE ON TOTAL KNEE REPLACEMENT (NIAMS)
--Approximately 300,000 total knee replacements are performed each
year in the United States for end-stage arthritis of the knee
joint, and the rate of total knee replacement procedures
increases each year.
--While these replacements have shown outstanding success,
controversies still exist regarding implant designs and
treatment. Research studies suggest that there are particular
challenges that must be addressed in patients with Parkinson's
disease, rheumatoid arthritis, and diabetes mellitus, as well
as total knee replacements in younger patients.
INCREASE SUPPORT FOR TRANSLATIONAL RESEARCH--MAXIMIZING THE RESULTS OF
BASIC RESEARCH TO IMPROVE PUBLIC HEALTH (NIAMS)
--To enhance and expand translational research, a new centers program
is currently being or would be created called centers of
research translation.
--These centers would pair basic and clinical projects in
investigator-initiated and directed research that is centered
around particular diseases. Different diseases might require
different translation mechanisms and strategies.
--The goal of the centers is the application of powerful tools and
knowledge from basic research to clinical research to improve
human health.
ADDITIONAL STUDIES ON INNOVATIVE THERAPIES FOR RHEUMATIC AND SKIN
DISEASES (NIAMS)
--Would expand a successful program that the NIAMS instituted in
fiscal year 1999.
--Would solicit investigator-initiated proposals for clinical trials
of innovative therapies or approaches for the treatment of
rheumatic and skin disease.
--The previous program has produced a number of ongoing clinical
trials that form the cornerstone of NIAMS-funded trials in
rheumatic diseases.
--It is anticipated that the trials may identify new therapies for
rheumatic and skin diseases.
OTITIS MEDIA (NIDCD)
--Would initiate Phase One trials of vaccine candidates.
initiate a definitive epidemiological study (nidcd)
--Would establish the role of prenatal exposure to cytomegalovirus in
progressive hearing loss during childhood.
COMMUNICATION DISORDERS (NIDCD)
--Would expand research to identify the hereditary basis.
hair cell degeneration and regeneration in the inner ear (nidcd)
--Would initiate new research to define the molecular basis.
ENHANCE CAPACITY FOR DISASTER/TERRORISM MENTAL HEALTH RESEARCH (NIMH)
--Could enlarge this currently small program to establish emergency
research protocols in conjunction with local public health
authorities and develop critically needed measures for use in
emergency/disaster research studies.
RESEARCH INITIATIVE ON PEDIATRIC BRAIN-BEHAVIOR DEVELOPMENT VITAL TO
DIAGNOSING AND TREATING CHILD MENTAL DISORDERS (NIMH)
--This initiative would result in the first-ever identification of
neuroimaging markers of specific child mental disorders which
will lead to improved diagnostics and potential for new
treatments in pediatric mental illnesses.
USE NIMH CLINICAL TRIAL NETWORKS TO LAUNCH TRIALS ON SIMULTANEOUS USE
OF MULTIPLE PSYCHIATRIC MEDICATIONS FOR THE SEVERELY MENTALLY ILL
(NIMH)
--Multiple medications is a widespread practice, but there is limited
scientific data about its health effects and implications.
ANOREXIA AND BULIMIA (NIMH)
--Would expand research on understanding eating disorders.
more research using brain imaging techniques (nida)
--Would study how exposure to drugs of abuse can affect the
developing human brain.
--Understanding precisely how brain changes relate to behavior,
especially during childhood and adolescence, is critical to
designing effective strategies for reducing drug use in the
United States.
--Better treatment strategies targeting children and adolescents
would be developed through these efforts.
COLLABORATIONS OF ESTABLISHED CLINICAL TRIALS NETWORK (CTN) WITH OTHER
ESTABLISHED NETWORKS AT NIH (NIDA)
--NIDA CTN staff and staff from NCI's Community Clinical Oncology
Program have discussed the possibility of jointly supporting a
smoking cessation study. This study would bring these two NIH
clinical research networks together in a synergistic
collaboration and test the networks' interoperability.
--CTN has also had discussions with NICHD to link the CTN to a
Network at NICHD that is studying adolescents and comorbidity.
ENHANCE OUR UNDERSTANDING OF THE GENETIC OR HERITABLE RISK FACTORS
ASSOCIATED WITH DRUG ABUSE USING THE CTN AS A VALUABLE RESOURCE (NIDA)
--The CTN could serve as a resource to acquire genetic information on
participants in clinical trials and to better characterize
different phenotypes associated with addiction.
--As gene variants are identified in association with drug addiction,
research could be conducted to determine how this genetic
information can be used to tailor medications to an
individual's genetic needs. This knowledge could be
incorporated into ongoing medications trials in the CTN.
EXPAND RESEARCH ON PREVENTING DRINKING BY YOUTH IN RURAL/SMALL URBAN
AREAS (NIAAA)
--Note: Partnerships have been formed with academic health centers,
abbreviated ``AHC,'' to conduct this research. AHC have in
place the disciplines required, as well as extensive service
networks in rural and small urban regions.
--Would expand the number of AHC sites that would conduct the
research.
--Would collect data on psychological and physical development, and
environmental/community circumstances, that are not routinely
collected in medical settings. A variety of biomedical,
psychosocial, and environmental factors act in concert to lead
to adverse outcomes, such as alcohol-related problems. We must
understand what all of these factors are and how they interact,
if we are to make real advances in preventing and treating
adverse outcomes of alcohol use among youth.
EXPAND RESEARCH AIMED AT DEVELOPING MEDICATIONS FOR ALCOHOLISM (NIAAA)
--Would develop animal models of response to alcohol that closely
predict efficacy of compounds to be tested in humans.
--Would create a clinical-trials network for early Phase II human
trials. These trials could yield relatively quick results and
can indicate which compounds are worth the resources required
for IND approval and Phase III trials. Partnerships would be
sought with pharmaceutical companies interested in compounds
found to be successful in NIAAA early Phase II human trials.
expand research on alcohol metabolism (niaaa)
--Alcohol metabolism plays a crucial role in alcohol dependence and
in alcohol-induced organ damage.
--Would form a bioinformatics data base, including data on gene
expression, proteomics, and metabolomics involved in alcohol
metabolism. This would be very important to our understanding
of which genes and proteins are involved in addictive behavior
and alcohol-induced organ damage, including cancer.
--In human clinical studies, use metabolomics and proteomics to
generate information on biomarkers of early/late tissue damage,
and identify targets for medication development.
--Using imaging technology, would determine if alcohol metabolism
occurs in the brain and, if so, determine what enzymes are
involved.
--Would identify all adducts (especially those that promote
autoimmune reactions) that result from alcohol metabolism, and
their roles in addictive behavior and organ damage.
--Would understand the interactions of alcohol metabolism with
comorbid conditions, such as obesity and diabetes.
TISSUE ENGINEERED HUMAN MODEL SYSTEMS (NIBIB)
--Would stimulate research and development in three-dimensional human
tissue model systems; engineered tissues for drug development;
and cell-based sensors for clinical diagnosis and treatment.
--Tissue engineering holds the promise to repair and/or replace
damaged organs.
--Tissue engineering strategies focusing on cell-based therapies, or
treatment modalities that rely on cells as the agents for the
treatment of diseases, have the potential to revolutionize
human therapeutics in the 21st century.
MINIMALLY-INVASIVE, IMAGE-GUIDED SURGERY (NIBIB)
--Would support research needed to rapidly develop computer-assisted,
image-guided microsurgery, which could replace traditional
surgery.
--Image-guided, minimally-invasive surgical procedures involve less
patient risk and pain and result in reduced hospital stays and
shorter recovery periods.
--Advances in surgical robots and microsurgical techniques could
enhance a surgeon's ability to perform complex tasks that
cannot be performed by hand.
--Could support: integration of existing technologies and development
of new technologies to navigate human anatomy, obtain
diagnostic tissues, localize and treat human disease and
injury, and monitor responses to surgical interventions.
chemistry of imaging agents and molecular probes (nibib)
--Could support exploratory projects for the synthesis, physical
characterization, and initial demonstration of feasibility for
clinical imaging agents for physiological, anatomical, and
molecular imaging.
--The ability to image molecular processes and cell function in vivo
provides an opportunity to understand biological processes as
they occur in their environment.
--Knowledge gained may be used to advance early-stage disease
detection and individually-tailored therapeutic interventions.
--The development of new clinical imaging agents requires focused
efforts by chemists and molecular biologists to discover new
compounds and materials suitable for in vivo imaging.
BRAIN-COMMUNICATION INTERFACE (NIBIB)
--Could develop technologies to create a more functional and
convenient system for restoring movement to paralyzed
individuals.
--Investigators have been successful in making Function Electrical
Stimulation (FES) a practical solution for restoring some
movement to paralyzed individuals.
--Current systems allow individuals with spinal cord injuries to
stand and breathe, and can restore functional hand grasp and
arm movement to some individuals with severe spinal cord
injuries.
--Recent developments in the technology of microelectrode design and
neurophysiological signal analysis open the possibility of
restoring greater control of motor function naturally--by
thinking about moving, a technique referred to as direct brain-
communication interface.
SUPPORT PLANNING GRANTS TO DEVELOP AND OPTIMIZE MODELS FOR DEPARTMENTS
OF CLINICAL RESEARCH WITHIN SCHOOLS OF MEDICINE (NCRR)
--Would provide tools to develop and test models.
RESTORE THE EXTRAMURAL RESEARCH FACILITIES IMPROVEMENT PROGRAM (RFIP)
FUNDS (NCRR)
--Would support construction and renovation projects at National
Primate Research Centers, animal research facilities and for
modem research laboratories at smaller institutions and
institutions within IDeA states.
ADDRESS THE SHORTAGE OF ADVANCED INSTRUMENTATION NEEDED TO PURSUE
CUTTING-EDGE BIOMEDICAL RESEARCH (NCRR)
--The High End Instrumentation program is the only NIH program that
provides support for research equipment that costs at least
$750,000; awards may be up to $2 million.
INTEGRATE TECHNOLOGY DEVELOPED THROUGH THE BIOMEDICAL INFORMATICS
RESEARCH NETWORK (BIRN) INTO CLINICAL RESEARCH AND OTHER NEW DOMAINS
OUTSIDE OF NEUROSCIENCE (NCRR)
--Some BIRN bioinformatics tools would be distributed and other tools
developed; hands-on workshops to inform investigators how to
use the tools for their research.
--Information technologies would be critical for scientific
discovery.
NCMHD COULD STRENGTHEN AND EXPAND ITS PROGRAMS (NCMHD)
--Loan Repayment Program
--Centers of Excellence Program
--Research Endowment Program
NCMHD COULD FULLY LAUNCH ITS COMMUNITY-BASED RESEARCH PROGRAM (NCMHD)
--Would fulfill this Congressional requirement.
TRAUMA AND INJURY (FIC)
--Would initiate a new program to support research training to
address the growing global burden of morbidity and mortality
due to trauma and injury related to road traffic accidents,
suicide and drowning, mental health consequences of war and
civil disorders, lack of emergency care and blood products and
other related conditions.
--Training supported by the new program would lead to prevention
strategies and interventions in wound healing, development of
synthetic blood products, development of low-cost imaging
technologies, mental health strategies, and epidemiology to
assess risk factors as well as other activities to reduce the
impact of trauma and injury to individuals, families and
communities.
--Would support the establishment of a global network of highly
meritorious research training centers to mitigate the impact of
trauma and injury.
BRAIN DISORDERS IN THE DEVELOPING WORLD: RESEARCH ACROSS THE LIFESPAN
(FIC)
--This program was begun through short term planning grants in fiscal
year 2003 with the intention to grow to full research project
grants in fiscal year 2005.
--The program supports collaborative research and capacity building
projects on brain disorders throughout life relevant to low-
and middle-income nations. Brain disorders represent a fast
growing proportion of the global burden of disease.
DEVELOP THE NEXT GENERATION OF INTERNATIONAL RESEACHERS (FIC)
--It is imperative that the U.S. scientific community be prepared to
tackle new threats while at the same time be positioned to work
in partnership with colleagues around the world on shared
problems.
--Would increase support to train U.S. medical students, graduate
students and post-doctoral students in methodologies needed to
tackle global health challenges.
--Would extend and intensify efforts in resource-limited nations to
provide clinically appropriate, cost-effective, and sustainable
care of direct health and economic benefits for the global
community and mitigate the threat of disease crossing borders
to affect the U.S. population.
COULD SIGNIFICANTLY EXPAND CAPABILITY TO ANALYZE, ANNOTATE, AND
CLASSIFY MASSIVE AMOUNTS OF RAW SEQUENCE AND PROTEIN DATA TO MAKE IT
READILY USABLE BY RESEARCHERS (NLM)
--Molecular biology is generating an unprecedented amount of genomic
data that have the potential to overwhelm researchers by sheer
volume.
--The protein classification project provides a valuable method to
deduce the function of newly discovered proteins, greatly
accelerating research in the molecular basis of disease and
therapy.
--The unique and comprehensive Reference Sequence Collection would
assist in studying the function of single genes and performing
large-scale comparative analyses of genes across multiple
organisms.
COULD ACCELERATE PROGRESS TOWARD DEVELOPMENT AND IMPLEMENTATION OF
CLINICAL VOCABULARY STANDARDS THAT ARE CRITICAL TO RE-ENGINEERING THE
CLINICAL RESEARCH ENTERPRISE (NLM)
--The inability to share clinical data across systems impedes
clinical research and is responsible for a significant number
of medical errors.
--An interlocking set of clinical vocabulary standards must be
developed that incorporate robust mappings between multiple
vocabularies used in clinical research and health care.
--Research, testing, and demonstration projects would help to
determine best practices for incorporating vocabulary standards
into clinical research, health care, and public health.
COULD WORK WITH OTHERS TO DEVELOP COMMON SOFTWARE PLATFORMS FOR
ADVANCED CLINICAL AND EDUCATIONAL APPLICATIONS OF THE VISIBLE HUMAN AND
OTHER IMAGE DATA SETS (NLM)
--Investments in building a Visible Human Functional Atlas of the
Head and Neck and associated public software tools establish a
strong foundation for developing applications software,
including simulation and modeling, useful in medical training
and treatment.
--Further research and testing would fully integrate the data,
software, and other technology in the teaching of embryology
and anatomy courses.
DEVELOP AND SUPPORT WOMEN'S HEALTH INTERDISCIPLINARY RESEARCH CENTERS
ESPECIALLY IN THE AREAS OF: (OD--OFFICE OF RESEARCH ON WOMEN'S HEALTH)
--Pharmacogenetic research that focuses on sex differences in drug
metabolism and biological pathways involved in the treatment of
diseases such as cancer, cardiovascular disease to provide the
much needed information to improve clinical outcomes, including
a better understanding of the impact of pregnancy or depression
on pharmacokinetics, pharmacodynamics, drug efficacy and
adverse effects of therapeutic agents.
DEVELOP AND SUPPORT A CLINICAL TRIAL TO TEST A PROMISING INNOVATIVE
TECHNIQUE THAT COULD REDUCE THE SIZE OF UTERINE FIBROIDS (OD--OFFICE OF
RESEARCH ON WOMEN'S HEALTH)
--Could result in less morbidity for the women who face potential
surgery or infertility as a result of this condition.
LAUNCH A TRANS-NIH INITIATIVE TO LEARN WHETHER EHEALTH TECHNOLOGIES ARE
EFFECTIVE IN ENHANCING HEALTH BEHAVIOR CHANGE AND CHRONIC DISEASE
MANAGEMENT (OD--OFFICE OF BEHAVIORAL AND SOCIAL SCIENCES RESEARCH)
--Consumers, patients and providers are increasingly using eHealth
applications for making health care decisions, and for
obtaining and dispensing services.
--These technologies offer a potentially low cost health delivery
system for underserved populations, as well as a means of
supporting provider adherence to evidence-based care.
Senator Specter. I want to finish this question before my
red light goes on to stay within the time limits. What is the
status and availability and adequacy of stem cell lines for
adequate stem cell research?
STEM CELL RESEARCH
Dr. Zerhouni. We have 17 cell lines now available. As you
know, we have worked aggressively in providing infrastructure
funding to all the sources that we knew were eligible for
Federal funding. NIH has done every effort to expand the
availability of lines. We have spent intramurally dollars to
create a characterization lab. We have gone from one laboratory
2 years ago to nine laboratories doing research. So we are also
realizing that training of scientists in these very difficult
methods is very important. So we are doing everything we can to
advance the field. So 17 lines are available to date, Senator.
Senator Specter. Well, I am going to violate the red light
for just one question. That is not enough, is it? Those are not
enough, are they? It is a leading question.
Are they?
Dr. Zerhouni. Well, we have a Stem Cell Task Force and Dr.
Battey really works very hard with the entire community to look
at what is the impact of what we need to do today of the number
of cell lines. The reports that we have is that we are learning
tremendously at a very high pace what are the advantages and
limitations. We are looking, for example, at these issues of
genetic stability and genetic diversity.
The Stem Cell Task Force at this point feels that we can do
a lot of research with what we have. Can we do all of the
research that will need to be done over the entire future of
stem cell research? No one can say that that would be the case.
Senator Specter. Well, I will pursue that with Dr. Battey.
I do not consider that an adequate answer, Dr. Zerhouni. It is
not often where I say your answer is not adequate, but I do not
believe that is an adequate answer.
We have been joined by the distinguished ranking member,
and I will yield to him at this time for 5 minutes for an
opening statement or questions or however he chooses to use his
time.
Senator Harkin. Mr. Chairman, thank you very much.
Senator Specter. We will have second rounds, but we have
Senator Stevens and Senator Cochran who are here.
STATEMENT OF SENATOR TOM HARKIN
Senator Harkin. Well, thank you very much, Mr. Chairman. I
apologize for being late. Some mornings you have to leave about
5:00 in the morning to get here because of the traffic.
It has been a privilege, Mr. Chairman, to work with you
over the last 14, almost 15 years, on behalf of supporting, as
you have said so many times, the crown jewel of our Federal
Government, which is the National Institutes of Health. I want
to thank you again for that working relationship, and I want to
thank you for your great leadership, Mr. Chairman, in doubling
the funding for NIH over that short period of time. It was a
pleasure to work with you to do that and to continue to work
with you on these crucial issues that impact the health and
welfare of all of our people.
Now, unfortunately, the budget we have submitted this year
is a far cry from the doubling years. I am concerned what it
means for the future health of NIH. We did not double the
funding for NIH to then fall off a cliff. But that is a real
possibility if we continue on with this kind of budget that we
have.
I want to welcome Dr. Zerhouni and the dozens of other NIH
leaders who have joined us. I do not always get the time to
hear from each of you, but I appreciate your being here and all
the work that you do.
All of you were involved in developing the NIH Roadmap. I
want to commend you for that effort. The initiative should help
break down the walls between the institutes and unite everybody
at NIH behind common goals. And, Dr. Zerhouni, I thank you for
your leadership in encouraging that and also for your
leadership in encouraging more risk-taking in the kind of
applications that NIH funds. We always have to be open to new
ideas. To the extent that I can, I hope to back you up. People
may say, well, why are you funding some of these far-out
things? Well, because sometimes we want to take a look at them.
And I really applaud you for doing that.
I just got here to hear a little bit about the stem cell
issue. We have discussed that many times before here. We know
that this research offers enormous potential to help ease the
suffering of people with Parkinson's and juvenile diabetes,
ALS, Alzheimer's.
I just had the occasion last evening to meet an old friend
of mine who I had not seen in several years. I found out that
he has Lou Gehrig's disease. It was just a startling thing for
me to see that last evening. His words to me were, you have got
to put more research into the stem cell research and find out
what is going on here. To see someone that you have known for a
long time and then you lost contact with him and then you see
him and you know they are not going to be around very much
longer and they are in middle stages of Lou Gehrig's disease,
it is a tough thing to see.
I am just concerned that the restrictive policies in this
research are delaying the day when these diseases could be
cured. Under the President's guidelines only those cell lines
generated before the arbitrary date of August 9, 2001 at 9
p.m.--not 9:30, not 8:45, but at 9 p.m., very arbitrary--can be
approved for federally approved research. The President said
then there were more than 60 eligible lines. Later we heard
there were 78. Now I just think I heard from you there were 17
that are available to researchers. Well, I will ask some
questions about this during my period of time.
These 17 were also grown on mouse feeder cells, all of
them, which raises questions whether or not they can ever be
used for any kind of human therapies.
Meanwhile, scientists in other countries are moving ahead,
but we cannot fund those. We cannot fund any of that kind of
research because those lines were developed after August 9,
2001 at 9 p.m. So again, I will get into that in my question
and answer period.
I thank you for letting me make my opening statement, and
whenever I can get a chance to ask questions, I will----
Senator Specter. Thank you, Senator Harkin. We will come
back to another round.
Senator Stevens.
Senator Stevens. Thank you very much.
Dr. Zerhouni, it is nice to see you here. I do not think we
have ever had an opportunity to put visuals on all of these
people that you have brought here with you today. So I want to
thank you for coming and apologize to them for taking their
time. I do not know of another group that is more important to
the future of our country than maybe now the intelligence
community might be that would have a similar impact in the long
range, but this long-range impact of you and your colleagues is
just staggering.
I heard the comments of my friend, Senator Harkin. Senator
Connie Mack came to me and urged me to support a concept of
doubling the NIH budget, and we have done that, Senator. So the
real question I think we have to do one of these days is
analyze what have we achieved with that money. I do think that
that is something that you and your assembled colleagues could
help us on. We are currently looking to increase other areas
now, the National Science Foundation for one and the
intelligence community for another. So the doubling of those
budgets in the next 5 years will take precedence I think
because of the circumstances that exist in the country.
PROSTATE CANCER
I am glad to see Dr. von Eschenbach here. My good friend,
Mike Phelps, reported you gave a tremendous speech at the
molecular imaging meeting in Orlando. Several of you know my
continuing interest in PET and its application to various areas
of your institutes. I do hope that we can be able to be very
aggressive in the use of that, the total molecular imaging
concepts, to Alzheimer's, which I believe is becoming a great
problem as the baby boom generation reaches retirement age.
But I have one specific question. Prostate cancer is also a
personal interest. I am a survivor now for 12 years. I would be
interested if Dr. von Eschenbach would comment upon finasteride
and what's going to happen to that clinical trial. I understand
the clinical trial was canceled and there were some problems.
Was the FDA a problem or was it that the high rate of tumor
growth in those taking the drug? What happened, Doctor?
Dr. von Eschenbach. Well, thank you, Senator, for that
important question because I think it really underscores and
points out not only the tremendous progress that we are making,
but also how the investment that you have been responsible for
in biomedical research is really now making it possible for us
to solve problems that before we did not even understand.
The issue with regard to the prevention trial of prostate
cancer using finasteride demonstrated that in fact the drug did
reduce the number of men who developed prostate cancer. So in
that regard, we stopped the trial because the endpoint had been
achieved. We in fact did get the answer and got the answer
earlier than we had hoped or anticipated and demonstrated the
protective effect of finasteride for a number of men who were
susceptible to prostate cancer.
What we also recognized in that trial was that although
fewer men developed prostate cancer on finasteride, the kind of
prostate cancer that they developed appeared to be more
virulent and more aggressive, and perhaps could even increase
their risk of progression or dying from prostate cancer.
So in addition to demonstrating the protective effect, what
we have now launched into is a subsequent set of studies to
understand the mechanisms of action and to determine the impact
on virulence. That is now an ongoing part of our research
investigation.
Senator Stevens. Thank you very much on that.
Mr. Chairman, I do have, unfortunately, on the schedule
several other subcommittees meeting. Again, I want to thank you
for bringing all of the directors of these institutes here. I
urge you to let them go quickly so they can go back to work.
Senator Specter. That concludes the hearing.
Senator Stevens. It concludes my time too. Thank you all
very much.
Senator Specter. Thank you very much, Senator Stevens.
I am going to step out for a moment down the hall to the
Judiciary Committee to see if I am needed for a quorum there. I
hope to return within the time allotted to Senator Cochran, but
if I do not, we will turn to Senator Harkin. Senator Cochran.
Senator Cochran. Mr. Chairman, thank you.
Dr. Zerhouni, we are very pleased with the fact that you
are exploring research possibilities in areas that have
previously been, I think, relegated to a fairly low priority.
Fundamental challenges such as understanding obesity, its
effect on health, what can be done to both treat those symptoms
and, more importantly, prevent that condition should be the
subject of research. I wonder what emphasis is placed in the
budget request with regard to research in this area.
OBESITY RESEARCH
Dr. Zerhouni. This is a very important topic to us.
Actually I would like to point out that NIH has been working on
obesity for over 10 years. I actually have a little graph here
that you could see whereby our investments started in 1996
because already at that time, NIH had predicted that the
obesity crisis will hit, and it became one of the top 10 topics
of research.
However, as you know, the rate of increase of obesity is
actually greater than what we expected, so we are increasing
our funding at the same level. In fiscal year 1996, we had $86
million. Next year we will have $440 million funding. Last year
I established a trans-NIH Obesity Task Force, led by Dr. Allen
Spiegel and Dr. Barbara Alving. They have come up with a new
strategic research plan for obesity, and despite the difficult
budget environment, we are going to increase our funding from
$400 million to $440 million in obesity research by $10
million. So we have almost quadrupled our investment in obesity
research while the rest of the NIH doubled to show you our
commitment to it and also our ability to see proactively where
research needs to be.
Senator Cochran. I hope you will take into account the
importance of concentrating some of this funding in areas that
suffer from this in a disproportionate way compared to the rest
of the country.
Dr. Zerhouni. Actually, Senator, this is one of the
priorities of the new plan. We are going to focus on childhood
obesity which affects rural areas and minority areas to a much
greater degree than other communities. So we will have an
implementation to be able to study that pattern early on in
life.
ROLE OF THE NATIONAL CENTER FOR COMPLEMENTARY AND ALTERNATIVE MEDICINE
Senator Cochran. One new phenomenon I know is the fact that
millions of Americans are using dietary supplements and herbal
products today. The National Center for Complementary and
Alternative Medicine is playing a role in understanding the
efficacy and the effects of these products. What are your plans
for research with respect to these products?
Dr. Zerhouni. If you allow me, I would like Dr. Stephen
Straus, who is the Director of the National Center for
Complementary and Alternative Medicine, to answer that. He has
very definite plans and great strategies for that.
Dr. Straus. Thank you. Mr. Cochran, our goal is to
characterize the complementary and alternative medicine (CAM)
products that Americans are using, understand why they have the
activities they do, and then prove whether they are safe and
effective. We are doing this in a multi-tiered approach, much
of which is conducted in partnership with the other NIH
Institutes and Centers because of their strong areas of
thematic expertise.
We are doing this with products that are used for
neurodegeneration such as ginko biloba. In that regard, we have
already enrolled, in partnership with the National Institute of
Aging, the National Heart, Lung and Blood Institute and the
National Institute of Neurological Disorders and Stroke, over
3,000 patients in the largest study ever mounted of an herbal
product, and at that time the largest preventative study
conducted for dementia. The goal is to prevent the onset of
Alzheimer's disease in otherwise healthy, aging Americans.
At the same time we are studying mechanism, and in your own
State, we have funded outstanding investigators at the
University of Southern Mississippi who are showing us several
different chemical constituents in ginko that prevent the death
of neuronal cells in the brain. These are our strategies.
Senator Cochran. Thank you very much.
THE NATIONAL INSTITUTE FOR BIOMEDICAL IMAGING AND BIOENGINEERING
I appreciate also the NIH's recognition of the role for new
technologies in the detection and treatment of disease. The
National Institute for Biomedical Imaging and Bioengineering
was created specifically to enhance research in this area. Has
this investment begun to show results, Dr. Zerhouni?
Dr. Zerhouni. I think so. One of the most important
meetings that the institute has had was actually organized at
the University of Mississippi. It was a national strategic
meeting to try to see where the direction of the field would
go. Dr. Pettigrew is really a great leader and I would like him
to comment, if you do not mind, Senator.
Senator Cochran. Thank you.
Dr. Pettigrew. Thank you, Senator, and I appreciate having
the opportunity to respond to that question.
There are many problems that physicians alone cannot solve.
There are problems that also require the input of quantitative
scientists. These would be scientists, which include not only
imagers and physicists but also mathematicians and computer
scientists.
We have been very successful, I am pleased to report, in
bringing physicians and quantitative scientists together to
translate the fundamental discoveries from the technologically-
based scientists into meaningful clinical applications for
patients. That is certainly our goal and we work very hard to
achieve that.
The progress to date has been quite remarkable given our
short history of only 2 years. I would like to tell you about
two examples in this area.
NIBIB'S PROGRESS
The first is the development of a new technology called
quantum dots. These are small nano crystals that are able to
identify specific cells of interest in the body, for example,
cancer cells in lymphnodes. Quantum dots could also be used to
identify the deposition of plaque in arteries.
We have also seen progress in an area that many people in
the audience might appreciate. No doubt people here have had
MRI scans. This is a marvelous technology, in fact, the subject
of the Nobel Prize in Medicine this year. But some of our
researchers have tackled one of the problems, which is the
speed with which these scans can be made. These researchers
have improved the speed of acquisition of images 10-fold.
Studies that used to take several minutes to acquire can now be
acquired in a matter of seconds. The value of this is not only
in improved patient comfort, but also in opening up additional
applications such as image-guided surgery where speed would be
very important.
These are examples of some of the technological innovations
that we have been pursuing and have begun to bring to fruition
for the benefit of us all.
Senator Cochran [presiding]. Thank you. Thank you very
much, Mr. Chairman.
Senator Harkin, do you have questions?
Senator Harkin. If you want to have a follow-up.
Senator Cochran. No. Go ahead. I am trying to carry out the
chairman's 5-minute rule here. No, go ahead, please proceed.
Senator Harkin. Okay, thanks.
STEM CELL LINES
I would like to get back to the stem cell issue, if I
could, and I would like to direct some questions to Dr. Battey.
I believe you are heading the Stem Cell Task Force.
Dr. Battey. That is correct.
Senator Harkin. Correct me if I am wrong, but I think you
have said that under the best case scenario, only 23 lines will
be available to federally funded scientists. Is it 23 or is it
17? I am a little confused there.
Be that as it may, even if it is 23, my question basically
is will 23 be enough to realize the full potential of stem cell
research?
Dr. Battey. Let me begin by addressing the numbers issue
that you have raised.
The number 17 refers to the number of cell lines that are
available today for Federal funding that can be widely
disseminated across the research community, cells that--if you
had a laboratory--you could order and get in your laboratory
for experiments. There are six additional derivations located
at institutions that hold NIH infrastructure awards for the
purpose of developing such cell lines, expanding them, getting
them ready to be distributed, going from a derivation to a
useful cell line that can be distributed. And we are hopeful
that all six of these will become distribution quality cell
lines. When you add 17 and 6, one arrives at the figure 23.
Now, there are 31 derivations located in five institutions
in Korea, India, and Sweden that are eligible for Federal
funding that are on the registry, but they have not sought an
NIH infrastructure award to develop such cell lines. So we do
not know the status of these derivations. They are privately
held and we are not privy to that information.
Senator Harkin. Let me get to my question there, Dr.
Battey. Will 23 or 17 be enough to realize the full potential
of stem cell research?
Dr. Battey. I do not know the answer to that question, but
there are reasons to be concerned. For example, there was a
published paper in December showing that when some of the cell
lines, some of the 17, are grown in some people's hands and
passaged for prolong periods of time, they develop karyotypic
abnormalities, chromosomal abnormalities. These abnormalities
are some of the same abnormalities that are seen on occasion in
teratocarcinomas, which are tumors of cells like embryonic stem
cells. That is an issue of great concern and will need to be
followed very carefully.
While I have to say I do not know whether or not we will be
able to do everything possible with either 17 or 23 or 46 or 98
or 321 cell lines, I do know that if there is additional
functional diversity it is difficult to imagine that more cell
lines would be detrimental to research progress.
MOUSE FEEDER CELL LINES
Senator Harkin. Could any of these 23 lines ever be used in
human therapy since they have all been developed on mouse
feeder cells?
Dr. Battey. We have discussed this issue at great length
with the Food and Drug Administration, who would be the
organization overseeing the safety and efficacy of any clinical
studies that were done with these cells, were these cells to
ever be returned to patients in transplantation in an effort to
treat some of these awful disorders like ALS that you have
spoken about. When we talk to the FDA about this, they say that
the mouse feeder cell layer is an issue and the issue of
whether or not a retrovirus or some other bad thing might have
been transferred from the feeder cell layer to the human
embryonic stem cells is an issue that must be explored.
It is not, however, a prohibitive issue. It is one of many
issues, including the history of the cells, where they have
been cultured, what kind of medium they have been cultured in,
if there have been any serum or other biological additives,
what the state and purity of those are. So there is no question
the feeder cell layer is a safety issue, but it is one of many
safety issues and I do not think should necessarily be drawn
out of that context.
Would it be preferable to have cells that were not growing
on mouse feeder cell layers? I think the answer to that
question is yes. Would it be preferable to have cells that were
grown in a medium that had nothing but completely defined
substances, purified additives? Absolutely. That would be
better. In fact, the NIH is funding investigators to try to
develop better culture conditions for human embryonic stem
cells with the goal of ultimately moving the cell lines into an
environment that poses less questions about biological safety.
ACCESS TO ADDITIONAL LINES
Senator Harkin. The other question I had was basically
would federally funded scientists benefit from having access to
additional lines. I think you basically answered that.
Obviously, the more you have and the more involved, I would
assume the better the research would be. You would have just
more lines out there to look at.
Dr. Battey. We will understand much better what the
significance of number of cell lines is when we have explored
to a greater degree what we can do with the cells that are
available and widely distributed for Federal funding. But as I
said before, it is difficult to argue that a greater number
with more potential functional diversity would be detrimental
to the research effort.
Senator Harkin. If they had access to additional lines--
lead me on. I just want to get a better understanding. How
would this be not detrimental if they had more?
Dr. Battey. Well, the problem here and the reason why I
cannot be more specific in answering this question is that we
are just at the beginning of exploring what we can do with the
cell lines that are eligible for Federal funding. We are just
beginning to learn the master switches that keep these cells in
a pluripotent state and allow them to replicate indefinitely in
the laboratory. We are just beginning to get our hands around
the growth factors and gene expression profiles that are
associated with differentiation towards a cell type that might
be interesting for a therapeutic application such as a
dopamine-producing neuron that might be lost in a patient with
Parkinson's disease or a motor neuron that will be lost by your
friend with ALS. We are only beginning to understand, and until
we know more about what we can do with the cells we have, what
their limitations are, what their possibilities are, it is hard
for me as a scientist in a fact-based manner to give you a
better answer than the one I have given, as much as I would
like to do that.
STEM CELL POLICY
Senator Harkin. Is it time to reevaluate the policy that
has been in effect since August 2001?
Dr. Battey. I think it is very important for there to be a
continued dialogue between scientists, the National Institutes
of Health, your subcommittee, and the administration about what
the state of the science is. The decision to evaluate a
presidential policy is a decision that is made at the level of
the White House. Our role in this process, as I understand it,
is to provide facts and information for the people who make
policy, and we have a regular dialogue with individuals in the
administration, as well as individuals on some of your staff
about the state of the science in human embryonic stem cells.
Just on a personal note, I am happy to come and talk to anybody
who has questions or wants to know more about the state of the
science in what I consider to be one of the most exciting areas
of science for the future of biomedical research.
Senator Harkin. Thank you very much, Dr. Battey.
Senator Specter [presiding]. Thank you, Senator Harkin.
Dr. Battey, the Congress also has a constitutional role in
setting national policy and that starts with this subcommittee.
Dr. Zerhouni and Dr. Battey, as the area of responsibility may
fall, we would like to have a comprehensive report on what has
happened to the original 60-some stem cell lines announced by
the President back in August of 2001 and what has happened to
them, how many are in private hands, how many of them are
tainted with mouse feeders, how many of them can be used, what
is happening at Harvard, what is happening in South Korea, what
is happening in other countries so we can make an evaluation as
to what the policy ought to be.
[The information follows:]
Stem Cell Research
Question. What is the status of human embryonic stem cell (hESC)
derivations listed on the NIH Stem Cell Registry? How many are in
private hands? How many have been grown on mouse feeder layers? How
many are viable?
Answer. All of the derivations listed on the NIH Human Embryonic
Stem Cell Registry are privately owned by 15 different companies or
academic institutions. The providers indicated by an asterisk (*) below
are recipients of the NIH Infrastructure award to develop, characterize
and distribute cell lines.
BresaGen, Inc., Athens, Georgia*
4 derivations
3 lines available
The cells in derivation BG04/hESBGN-04 failed to expand into
undifferentiated cell cultures.
Cell & Gene Therapy Research Institute (Pochon CHA University), Seoul
Korea
2 derivations
0 lines available
Cellartis (formerly Cell Therapeutics Scandinavia), Goteborg, Sweden*
3 derivations
2 lines available
Cell line SA03/Salgrenska 3 was withdrawn by donor.
CyThera, Inc., San Diego, California*
9 derivations
0 lines available
The cells failed to expand into undifferentiated cell cultures.
ES Cell International, Melbourne, Australia*
6 derivations
6 lines available
Geron Corporation, Menlo Park, California
7 derivations, all duplicates of Wisconsin Alumni Research Fdn.
derivations
Goteborg University, Goteborg, Sweden*
16 derivations, reported to have not been exposed to mouse feeder
layers
0 lines available
Karolinska Institute, Stockholm, Sweden*
6 derivations
0 lines available
The cells failed to expand into undifferentiated cell cultures.
Maria Biotech Co. Ltd.--Maria Infertility Hospital Medical Institute,
Seoul, Korea
3 derivations
0 lines available
MizMedi Hospital--Seoul National University, Seoul, Korea*
1 derivation
1 line available
National Centre for Biological Science/Tata Institute of Fundamental
Research, Bangalore, India
3 derivations
0 lines available
Reliance Life Sciences, Mumbai, India
7 derivations
0 lines available
Technion-Israel Institute of Technology, Haifa, Israel*
4 derivations
2 lines available
University of California, San Francisco, California*
2 derivations
2 lines available
Wisconsin Alumni Research Foundation, Madison, Wisconsin*
5 derivations
5 lines available
Of the 78 entries on the Registry, 71 are from independent embryos
and 7 are duplicates located at both WiCell (Wisconsin Alumni Research
Fdn.) and Geron. The Geron cell lines are not being widely distributed
to the research community.
Of the 71 independent derivations:
--16 have failed to expand into self renewing, pluripotent cell lines
(9 at CyThera, 1 at BresaGen, 6 at Karolinska), and 1 line was
withdrawn by the donor at Cellartis (formerly Cell Therapeutics
Scandinavia, CTS). NIH provided Infrastructure support in
failed attempts to expand these 16 derivations into
distribution-quality cell lines.
--Of the remaining 54 independent derivations, 21 are available for
shipment, after expansion and characterization using NIH
Infrastructure grant awards. The 21 that are currently
available are:
BresaGen, Inc.--BG01, BG02, BG03
Cellartis--SA01, SA02
ES Cell International--ES01, ES02, ES03, ES04, ES05, ES06
MizMedi Hospital--MI01
Technion-Israel--TE03, TE06
UCSF--UC01, UC06
WiCell--WA01, WA07, WA09, WA13, WA14
--Of the remaining 33 independent derivations, 2 more are at
institutions with NIH Infrastructure awards. If these 2 were
developed into distribution quality cell lines ready for
shipment, there would be 23 independent cell lines available to
the research community. The 2 cell lines under development are:
Technion-Israel--TE04, TE07
--The remaining 31 independent derivations are all at institutions
located outside of the United States that have not applied for
NIH Infrastructure awards to develop their cell lines. Any
plans to develop these derivations into cell lines that are
available to the research community are unclear at this time.
The 31 derivations at institutions that do not have
Infrastructure awards are:
Pochon CHA (Korea)--2 derivations
Goteborg Univ. (Sweden)--16 derivations
Maria Biotech (Korea)--3 derivations
National Centre for Biological Sciences (India)--3 derivations
Reliance Life Sciences (India)--7 derivations
As far as we know, all derivations have been exposed to mouse
feeder cells, with the exception of the 16 derivations at Goteborg
University (Sweden).
Information on the detailed characteristics of each of the
derivations is available on the NIH Human Embryonic Stem Cell Registry,
http://escr.nih.gov.
Question. What is Happening at Harvard University?
Answer. On March 25, 2004, Harvard University announced the
derivation of 17 hESC lines in an article published in the New England
Journal of Medicine. Funding for the derivations and distribution of
these lines is being provided by the Howard Hughes Medical Institute,
Juvenile Diabetes Research Foundation and Harvard University.
On April 23, Harvard University announced the establishment of the
Harvard Stem Cell Institute. According to Harvard, the Institute will
encourage adult and embryonic stem cell research using both animal and
human stem cells. The Institute has two co-directors: Harvard Medical
School Professor David Scadden, who also directs Massachusetts General
Hospital's Center for Regenerative Medicine and Technology, and Douglas
Melton, the Thomas Dudley Cabot Professor of the Natural Sciences and a
Howard Hughes Medical Institute investigator.
Research at the Institute will be focused on five areas of disease
for which stem cell therapy seems most promising. The diseases all
result from some sort of organ or tissue failure and include: diabetes,
neurodegenerative diseases, blood diseases, immune diseases,
cardiovascular disease, and musculoskeletal diseases.
Although research on the 17 new human embryonic stem cell (hESC)
derivations are not eligible for Federal funding, NIH is currently
supporting several scientists at Harvard University whose hESC research
use lines eligible for Federal funding. Dr. Doug Melton is working to
identify the genes involved in hESC self-renewal and differentiation.
Dr. George Daley is studying hematopoietic development from hESCs. Dr.
Howard Green is working to develop the culture conditions to coax hESCs
to become the keratinocytes that make up human skin(s epidermis. Dr.
Jeffrey Harper is analyzing the signals that control hESC division.
Question. What is Happening in South Korea? What is Happening in
Other Countries?
Answer. On February 12, 2004, South Korean researchers published
the first scientifically credible report of the creation of a cloned
human embryo in the laboratory by means of somatic cell nuclear
transfer (SCNT) (Science 303: 1669-1674.) These scientists, supported
by the South Korean government, then used these cloned embryos to
establish a human embryonic stem cell line. They combined the DNA of a
woman's ovary cell with her donated egg, from which the nucleus had
been removed, and then stimulated the newly combined cell to divide.
The resulting very early embryo was then allowed to develop to the
blastocyst stage (five to nine days), at which point it was
disaggregated and the highly potent stem cells of the inner cell mass
were removed. These stem cells were then treated to produce a stem cell
line to be used for various kinds of biomedical research. Subsequent to
the publication of the SCNT study, the South Korean government voted to
ban the creation of cloned human embryos, but might allow cloning for
biomedical research on a case-by-case for medical treatment subject to
approval by a National Bioethics Advisory Commission. Scientists will
be permitted to use spare frozen embryos, left over from infertility
treatments and kept in laboratories for at least five years, for
limited stem cell research into treatments for hard-to-cure diseases.
The regulations banning human cloning are expected to come into effect
after President Roh Moo-hyun signs the bill. The regulations on stem
cell research will go into effect in 2005.
OTHER INTERNATIONAL STEM CELL EFFORTS
International Society for Stem Cell Research (ISSCR).--The
International Society for Stem Cell Research is an independent,
nonprofit organization established to promote and foster the exchange
and dissemination of information and ideas relating to stem cells, to
encourage the general field of research involving stem cells and to
promote professional and public education in all areas of stem cell
research and application. Opinions on the legitimacy of experiments
using human embryos vary among members of the European Union (EU)
according to the different ethical, philosophical and religious
principles in which they are grounded. EU member states have taken very
different positions on the regulation of human embryonic stem cell
research and cloning for biomedical research. More information about
the regulations and policies of EU members can be found on the website
of the ISSCR at the following link: http://www.isscr.org/scientists/
legislative.htm.
The International Stem Cell Forum (ISCF).--The ISCF was founded in
January 2003 to encourage international collaboration and funding
support for stem cell research, with the overall aim of promoting
global good practice and accelerating progress in this vitally
important area of biomedical science. The Forum's long-term aim is to
help stem cell scientists achieve a range of revolutionary medical
advances that will benefit people throughout the world. The ISCF is led
by the United Kingdom's Medical Research Council and consists of 14
leading supporters of stem cell research from around the world. Member
organizations are based in the United States, Finland, Australia,
Canada, Germany, France, Israel, Netherlands, Japan, Singapore, Sweden,
Switzerland, and the United Kingdom. Within ISCF, the United States is
represented by the NIH. The Juvenile Diabetes Research Foundation
International (JDRF) is also a member of the ISCF. One short term goal
of the ISCF is to compare different stem cell lines from the member
organizations. As part of this goal, NIH's federally approved stem cell
lines will be compared to those of other member organizations.
Information about the stem cell research efforts of the member
organizations can be found on the website: http://mrc.live.tmg.co.uk/.
Senator Specter I have discussed it with the President and
he has a view on it. The facts are very important in
formulating all of our views. So let us proceed to bring all
the facts to this subcommittee.
Dr. Zerhouni. You have my commitment to do so, Senator.
BIODEFENSE AGENTS
Senator Specter. Thank you very much.
On the issue of biodefense, the concerns about another
attack are with us imminently as we sit here. We have seen an
acceleration of the venom and hatred from Wahabes and Islam
fundamentalism and we have a long chronology of attacks going
back to 1983 when 283 Marines were killed in Lebanon, what
happened in Mogadishu, what happened in Africa in August 1998,
what happened with the Cole, what happened on 9/11. We have to
be prepared.
Dr. Fauci, you and I have discussed this on other
occasions. This year's request includes $1.7 billion toward
biodefense research activities. What are the principal
bioweapons that we are working to defend against?
Dr. Fauci. The principal bioterror agents that we are
involved in pursuing from the standpoint of developing
countermeasures remain the category A agents that we have
discussed before this committee on several occasions. High
among those are still smallpox, anthrax, botulism toxin,
tularemia plague, and the hemorrhagic fevers including Ebola.
We are pleased to report, as Dr. Zerhouni mentioned in his
opening statement, that over the past year with the resources
that this committee has generously given us, we have made
extraordinary progress in having available, either already in
the stockpile or in contract on its way either in phase I/II or
purchase, countermeasures in the form of vaccines for smallpox,
anthrax, and soon Ebola.
Senator Specter. If there was to be an attack on anthrax,
how well prepared are we?
Dr. Fauci. We are extraordinarily better prepared today
than we were in the anthrax attacks in the fall of 2001 with
the following issues. A, the stockpile of antibiotics right now
to treat prophylactically for the entire 60-day period with
ciprofloxacin or doxycycline is now able to meet a substantial
attack, God forbid that were to occur. And also, we are now
well into the development of the second generation of a
recombinant protective antigen anthrax vaccine that could be
used to vaccinate people who would go in to clean up, the
hazmat people, health workers, and those who would be required
to have an extended period of antibiotics. So the anthrax
situation is dramatically different than it was in this
building a year and a half, 2 years ago.
Senator Specter. Adequate?
Dr. Fauci. I believe adequate. I think we still have a ways
to go on every issue, but the progress that is being made
particularly in the arena of anthrax is striking.
Senator Specter. My red light is about to go on. So I would
like you to supplement in writing the details as to the other
threats, what we have done, whether it is adequate, and what
more needs to be done.
Dr. Fauci. I would be happy to do that.
Senator Specter. This is something we have to address
forcefully and promptly.
Dr. Fauci. Will do.
[The information follows:]
Research in Medical Countermeasures Against Category A Biological
Agents
The accompanying table provides a summary on the status of research
and development of medical countermeasures for Category A biological
agents. These biological agents and the countermeasures that are
currently available for them are identified in the first two columns.
Recent NIAID accomplishments are identified in column three (complete
details of these and additional accomplishments can be found in the
NIAID Biodefense Research Agenda for CDC Category A Agents Progress
Report).\1\ Candidate countermeasures that are at an advanced research
stage where rapid development of the countermeasures is scientifically
feasible are identified in the fourth column. Finally, many of the
countermeasures that are the focus of early research efforts are
identified in the last column.
---------------------------------------------------------------------------
\1\ See http://www2.niaid.nih.gov/Newsroom/Releases/
biodefensereport2003.htm for a detailed report on research progress
made to date for CDC Category A Agents.
---------------------------------------------------------------------------
I would like to add that we continue to support a national,
comprehensive biodefense research and development program. It includes
the development of other biodefense countermeasures to combat
Categories B and C biological agents, as well as a broad range of basic
research activities.
Senator Specter. Senator Harkin.
Senator Harkin. Thank you, Mr. Chairman.
FUNDING OF RESEARCH GRANTS
Dr. Zerhouni, our staff has brought to our attention this
issue of the number of research grants that we are funding this
year. It is a question we always ask. What are we doing in
terms of the number of grants and the funding for these grants?
I have found--and you correct me if I am wrong on this--
that fiscal year 2004 marked the first time in 8 years that the
number of new competing grants went down. It dropped from
10,393 in fiscal year 2003 to 10,135 in fiscal year 2004. That
is the bad news. We might say, well, but the good news is the
President's 2005 budget calls for raising that number back to
the 2003 level of 10,393. So I said, okay. How do we do that?
As you know, when researchers get approved for NIH grants,
for the second, third, fourth years, there is an automatic 3
percent increase. Well, what I found out is that this
longstanding commitment by NIH to these researchers is
necessary so that they can pay their staff and give them their
annual salary increases or get new equipment and so forth in
the second, third, and fourth years. Now, that is 3 percent.
And this year's budget calls for an increase of 1.9 percent to
the second, third, and fourth year researchers. As a result,
the researchers will receive less money than what NIH committed
to providing them.
I am wondering about the effect this is going to have.
Could it force them to change the scope of their work in
midstream?
Now, again, I think that you and all of us are opposed to
breaking NIH's commitment to its grantees. Once you make a
commitment, you make a commitment. And I am concerned that this
budget is changing this policy, and I am wondering why are we
changing this policy. Why are we going to 1.9 percent rather
than 3 percent?
Dr. Zerhouni. These are very important questions and those
are the questions we have grappled with in a very difficult
budget environment and we had to make tough choices.
But let me address your first question which was that a
decrease between 2003 and 2004 and then recovery in 2005 in
numbers of grants. Fiscal year 2003 was the last year of the
doubling of the budget.
Senator Harkin. Right.
Dr. Zerhouni. We actually gave more grants in 2003 than we
planned to do so that is why the number in 2003 was higher. In
2004, we were planning on keeping that level or even go up a
little bit, but certain budgetary events occurred.
One, was the .59 percent cut across the board. That was in
conference.
Second was the reshifting of extramural construction, $119
million we had not requested. It was then put back into the
extramural construction.
Last but not least was what we call the planning and
evaluation tap, 2.2 percent of the NIH budget is used to fund
AHRQ, for example. So all of these elements decreased the funds
available for the grant pool in 2004.
Now we come to this year and we have a budget envelope of
2.6 percent. So we had to make tough choices.
I agree with your policy principle. This is something that
I have told all the Institute and center directors--that our
word is our bond. We should really commit to maintaining
research grants at least at an inflationary level so that they
do not lose the ability to purchase research, if you will.
SUCCESS RATES
But on the other hand, we also have a marked increase in
terms of applications and new scientists are coming to us
asking for grants. So we had to make a tough decision. I have
the information here to show you on the screen. If you looked
at our success rate at the beginning of the doubling, our
success rate was 32 percent here. The number of applications we
received in 2001 was 28,000. Senator, the number of
applications we are receiving is now 38,000. This year alone
our Center for Scientific Review will receive 66,000
applications for all types of grants for NIH as well as some
from CDC, AHRQ, FDA, and SAMHSA.
Senator Harkin. Excuse me, Dr. Zerhouni, but that 38,000
and the 37,000 and the 34,000 I see, are those the ones that
actually make it through the peer review process?
Dr. Zerhouni. Those are the ones that are applied for. They
are new and competing in that year. Only one-third of them will
get funded.
So, for example, if you go back to 2001, Senator, we had
28,000 grants. Thirty-two percent of those were funded. Then we
had 30,000 applicants. Thirty-one percent of those were funded.
And then in 2003, we had 34,700 applications.
So from my standpoint, as you look at the budget and you
look at the number of scientists out there who are coming up
with great ideas, we had to make a choice. Can we shave the
cost increases to allow more of these increasing numbers of
scientists to apply and be successful? So those are the
tensions, Senator, that I had to deal with in making the tough
decisions.
Senator Harkin. Well, I understand the dilemma you were
faced with. I guess under the budget we have got a choice,
either increase the number of new grants and cut back on the
increases for those that are already approved, or keep the
increases in and not have new grants.
Dr. Zerhouni. That's right.
Senator Harkin. That seems to be the dilemma.
Well, I do not know. Maybe we made the right decision, but
I just think we all ought to be aware, Mr. Chairman, of the
tradeoff that we have made with this budget. Now, I am
preaching to the choir here because this person right next to
me here keeps going on the floor trying to get our budget up
for NIH and I have backed him every time we have tried to do
that. But because of this budget, you have had to make almost a
devil's choice here in terms of the tradeoff. As you say, you
want to keep your word. You want to keep your commitment to
these researchers. But then the President's budget--it is his
budget--wants to have all these new starts, so then you have to
trade that off. I think that is why we need to actually get
this budget back up again so that that does not happen.
PROJECTING OUT-YEAR BUDGETS
Now, I am particularly concerned, as I said in my opening
statement, about the years ahead. According to OMB, NIH's
budget is expected to drop in actual dollars by 2 percent in
fiscal year 2006. If that goes through, do we have any idea
what that is going to mean in the number of grants and this
dilemma we are facing right now? What is that going to mean?
Dr. Zerhouni. At this point I heard the same thing that you
heard. So we queried and we asked are there decisions made in
our out-year budgets. To this moment, I am not told of any
formal decisions that were made by OMB that would imply those
cuts in the NIH budget.
Senator Harkin. I got it from OMB.
Dr. Zerhouni. I understand. There were projections, but
from the standpoint of our interactions with OMB, we are told
that those are projections and estimates that were made, not
policy decisions.
Senator Harkin. Well, I know they are projections. This is
what OMB is projecting. I have got the figures right here, a 2
percent cut in fiscal year 2006. That is next year. That is
what we are going to be confronting next year, and we are going
to be here next year.
So, again, I am just asking. We need some information. What
would this mean if OMB's projection goes through and we have
this 2 percent cut in fiscal year 2006 and we are confronting
that, what does it mean for grants, commitments to researchers,
size of grants? I mean, we need to know what the impact of that
is going to be.
Dr. Zerhouni. We definitely are willing to provide you with
those projections from the standpoint of the agency, and I will
provide that to you for the record.
Senator Harkin. I do not need them right now, but we are
going to need them sometime because we are going to start
getting into this sometime this year. But we should have some
handle on that as to what that might mean, so that we can at
least, as we have been saying here, get the facts out as to
what this would mean. Before the budget actually comes out is
what I am saying, we ought to have this out there so people
that are devising the budget know what it is going to mean.
Dr. Zerhouni. But again, we checked and those figures are
not decisional figures. They are not decisions made. They are
projections.
Senator Harkin. I understand that, but we have got to know
what those projections mean in real terms if in fact they
follow through on them.
Dr. Zerhouni. Definitely.
[The information follows:]
2 Percent Decrease in Fiscal Year 2006
As indicated, while there are mechanically calculated numbers in
the OMB computer system that reflect the Administration's overall
budget targets in the outyears, no specific funding decisions have been
made for NIH or most other domestic programs. In answer to your
question, if the NIH budget were to decrease by 2 percent in fiscal
year 2006 from the fiscal year 2005 Budget Request, the number of
competing research projects grants (RPGs) would decrease by an
estimated 2,000 to 2,500 depending on the average cost assumptions
used.
Senator Harkin. Thank you, Dr. Zerhouni. Thank you, Mr.
Chairman.
Senator Specter. Thank you, Senator Harkin.
OBESITY RESEARCH
Dr. Zerhouni, the issue of obesity is one of enormous
importance. In 15 years, obesity has increased by over 50
percent among adults; in 20 years, 100 percent among children
and adolescents. We would like a written response as to what
can be done by NIH, how this subcommittee might be effective on
diet or education. We have both Health and Human Services and
Education to try to confront this growing problem.
[The information follows:]
Obesity Research
The NIH Obesity Research Task Force, which was established in April
2003 to accelerate research on this escalating health problem, has
developed a Strategic Plan for NIH Obesity Research in broad
consultation with external scientific and lay experts. We believe that
implementation of this Plan is the best way that the NIH can contribute
to arresting the obesity epidemic. Combating obesity must be a broad
national effort to which the NIH can contribute new and important
scientific insights. As noted, the fiscal year 2005 President's Budget
request for the NIH reflects a 10 percent increase for obesity
research, which would bring total NIH funding for this area to $440
million. The proposed 10 percent increase includes additional new
funding to begin implementation of obesity research in specific areas
identified in the Strategic Plan because of their scientific
opportunity and public health challenge. With respect to your specific
reference to diet and education, the NIH has also recently created a
new obesity research website http://www.obesityresearch.nih.gov), which
contains links to science-based information generated by many of the
NIH Institutes and Centers for the public, patients, and providers. Two
helpful programs are the NIDDK's Weight Control Information Network and
the NHLBI's Obesity Education Initiative.
MEDICATION TO LOWER PLASMA LIPOPROTEIN (A) [LP(A)]
Senator Specter. Last year I asked Dr. Lenfant about
research on medication to lower Lp(a). Dr. Alving of the Heart,
Lung and Blood Institute, is there anything new that you can
inform the subcommittee about on the status of research toward
a medication to lower Lp(a)?
Dr. Alving. Yes. Thank you very much.
Since the past year, there has been no really new
information on Lp(a). It is still defined as an emerging risk
factor. But there has been certainly very new information on
the importance of lowering LDL, even below the guidelines of
less than 100 milligrams per deciliter.
Senator Specter. We see the LDL research all the time on
the front pages.
Dr. Alving. Yes.
Senator Specter. But how about Lp(a)? That has been
identified as a very problemsome factor. We have asked you
about it repeatedly. What efforts are you making to identify
what can be done about it?
Dr. Alving. The efforts to identify it have been in terms
of our ATP III Guidelines Committee, which has been reviewing
all of the literature and has been closely focused on the
latest guidelines and the latest research.
Senator Specter. Aside from reviewing literature, is there
active research being undertaken in the field?
Dr. Alving. There are R01 grants that include Lp(a), but it
has not really been able to be classified as a true risk
factor. But what I would like to do----
Senator Specter. How many grants?
Dr. Alving. What I would like to do is reply for the record
with an actual listing of the R01 grants so that I can give you
very specific information about all of our research.
Senator Specter. That would be fine. We would appreciate it
if you would specify the grants, what they are doing, what
their success has been, what more you need to do.
Dr. Alving. Yes. I will be happy to do that, Senator.
[The information follows:]
Research Activities on Lp(a)
The NHLBI supports a variety of grants and contracts related to the
cardiovascular disease (CVD) risks associated with elevated
concentrations of Lp(a), factors that influence Lp(a) levels,
mechanisms by which Lp(a) may affect CVD, and Lp(a) metabolism.
Beginning in 2005, the NHLBI will support measurement of Lp(a) in the
next four years of the National Health and Nutrition Examination
Survey.
The NHLBI supports the following R01 grants related to Lp(a):
--APEX: Adiposity Prevention by Exercise in Black Girls (Medical
College of Georgia).
--Biology of Proteolytic Derivatives of Lp(a) (University of
Chicago).
--Epidemiology of Coronary Artery Calcification (University of
Michigan at Ann Arbor).
--Genetic Determinants of Lp(a) Concentration (University of Texas
Southwestern Medical Center).
--Genetic Epidemiology of Blood Lipids and Obesity (University of
Pittsburgh).
--Lifestyle, Adiposity, and Cardiovascular Health in Youths (Medical
College of Georgia).
--Macronutrients and Cardiovascular Risk (Johns Hopkins).
--Regulation of Lp(a) Metabolism in Humans (University of California-
Davis).
The Institute also supports a K08 clinical investigator development
award for a project on Lp(a), Homocysteine, and Cardiovascular Risk in
End-Stage Renal Disease (Johns Hopkins).
Lp(a) is a subject in several epidemiologic studies supported
through NHLBI contracts:
--Atherosclerosis Risk in Communities Study (ARIC) (Baylor College of
Medicine, Johns Hopkins, Mississippi Medical Center, University
of Minnesota--Twin Cities, University of Texas Health Sciences
Center, University of North Carolina at Chapel Hill).
--Cardiovascular Health Study (CHS) (Johns Hopkins, University of
Washington, University of Vermont, University of Pittsburgh,
University of California--Davis, University of Wisconsin, Wake
Forest University).
--Coronary Artery Risk Development in Young Adults Study (CARDIA)
(Harbor-UCLA Research and Education Institute, Kaiser
Permanente Division of Research, Northwestern University,
University of Minnesota--Twin Cities, University of Alabama at
Birmingham, University of California--Irvine).
--Framingham Heart Study (Boston University Medical Center).
--Jackson Heart Study (Jackson State University, Mississippi Medical
Center, Tougaloo College).
Two NHLBI-supported cooperative agreements related to
cardiovascular disease risk factors in Alaska Natives and Native
Americans also include Lp(a) measurements:
--Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN)
(MedStar Research Institute).
--Strong Heart Study (MedStar Research Institute, Missouri Breaks
Research Inc., Southwest Foundation for Biomedical Research,
University of Oklahoma Health Sciences Center, Weill Medical
College of Cornell University).
In 1998, the NHLBI initiated a 4-year Lp(a) Standardization Program
to enable accurate and consistent measurement that may help to
reconcile various findings. Following completion of the program, a
workshop was held to present the new results, evaluate current
understanding of Lp(a) as a risk factor for CVD, and design future
studies. The workshop report was published in the journal Clinical
Chemistry in November 2003.
In summary, the following statements can be made with respect to
Lp(a).
--In general, research has found only a modest association between
Lp(a) levels and CVD risk.
--Compared with plasma LDL, Lp(a) concentrations are relatively
resistant to alteration by pharmacologic and lifestyle
interventions.
--Lp(a) is a complex and heterogeneous protein, and measurement
challenges have created difficulties in comparing data from
different sources or assessing the impact of findings on the
severity of disease.
--Measurement of Lp(a) is not currently recommended as part of CVD
risk assessment in patients.
Senator Specter. We are going to try to bring this hearing
to a close, following Senator Stevens' admonition. We are
keeping a lot of scientists away from their laboratories here
and there is a lot of work to be done.
SPINAL MUSCULAR ATROPHY
Dr. Landis, on the issue of spinal muscular atrophy
therapeutics, could you bring us up to date on when that will
be ready for clinical trials?
Dr. Landis. We are actually running three pilot clinical
trials right now based on previous data. This is a network that
is set up by Susan Iannaccone. In addition, the new project
looking at additional compounds is well underway. The advisory
committee has created a flow plan, and the first set of awards
to come up with an animal model that would be used for
preclinical studies will be awarded in the next week or 2.
In addition, two further solicitations have been put out,
one that would that would look for cell culture models again
being used to solicit better mechanisms to look at therapeutic
molecules, and the second to come up with a satisfactory way to
measure the protein that is missing. So I think, between what
pilot trials are ongoing and this new therapeutics initiative,
we are making significant progress.
Senator Specter. Would you supplement your answer with a
written report about how you project activities of NIH to
proceed in this line looking toward some ultimate answer?
Dr. Landis. I would absolutely be pleased to do so.
[The information follows:]
Spinal Muscular Atrophy
The NINDS has developed a new program, called the SMA Project, to
accelerate the development of therapies for this disease. The SMA
Project uses a performance-based, milestone driven, contract mechanism
to shorten the cycle time from recognition of a need or opportunity for
research to getting research underway on those issues and finding
answers. We awarded the primary contract in September 2003. This is an
extremely ambitious project in a very challenging area of medical
science, and scientific progress is not predictable. However, we have
explicitly designed the SMA Project to respond quickly to unanticipated
obstacles and to emerging opportunities, in the hopes of achieving our
goal of identifying a therapeutic candidate for SMA, and completing the
required preclinical research and development by late 2007.
One very important aspect of this program is that we are
coordinating the research centrally, calling for targeted research
projects to meet specific needs identified by an overall plan, and
carefully monitoring progress. The program is guided by a superb
Steering Committee, with scientists from academia, industry, the Food
and Drug Administration, and the intramural and extramural programs at
the NINDS. The Committee has already developed a plan and a sample
timeline showing all of the steps necessary to meet the goal of
bringing a candidate therapeutic to investigational new drug (IND)
status that is necessary for clinical trials, within four years. The
sample timeline and other detailed information about this program are
available to the public on a website at http://smaproject.org.
A crucial aspect of the SMA Project is the rapid turnaround from
identifying a research opportunity or need, to solicitation for
research proposals, to funding. The first targeted solicitation for
research subprojects, focused on mouse models for testing therapies,
was issued in December of 2003. These applications have been reviewed,
and expect awards to be issued by June 1, 2004. Two further
solicitations were issued in March, on cell culture models and on
measuring the crucial protein that is lacking in SMA. Full length
proposals are due in May, notification of subcontract awards is
scheduled for June and funding for July. These initial proposals have
been focused on generating the necessary research tools to identify a
candidate treatment that has the highest probability of success in the
clinic. Future solicitations will be aimed at stimulating new drug
identification; the development of gene therapy; and establishing
centralized testing facilities to conduct the activities required in
the flow plan, such as evaluating compounds in animal and cellular
models of SMA.
In addition to the contract-based SMA therapeutics development
project, we are currently supporting the short term, open label pilot
clinical trials, being conducted by Dr. Iannaccone, of three drugs that
have shown promise either in patients or in models of SMA. We will be
looking to see if these results warrant larger trials. We are also
planning a workshop on clinical trials for SMA to be held later this
year. This workshop is intended to ready the SMA clinical community to
test interventions that result from the SMA Project, by promoting
collaboration and high quality trial design. In preparation, we are
moving forward to work with the community on identifying and evaluating
drugs now available that may slow the progression of SMA and be ready
for testing in clinical trials.
So, we are exploiting the best existing opportunities in the short
term for slowing the disease, and at the same time we are developing
the best possible treatments for the future through the SMA Project.
Finally, I want to emphasize that the SMA Project is not replacing our
traditional investigator-initiated grant programs and our intramural
program on SMA; we are continuing to support this research as well. We
also have extensive research programs in cross-cutting areas such as
gene therapy, drug screening, and stem cells that may ultimately have
an impact on SMA.
Senator Specter. Thank you. Dr. Spiegel, in your field we
had a high visibility attention-getter when NBA basketball star
Alonzo Mourning was seeking a kidney transplant and was forced
to retire early on glomerular disease that damages filters in
the kidney that cleanse the blood. We were asked to hold a
separate hearing which was just too much to do. Could you give
us an update on where that stands?
Dr. Spiegel. Yes, Senator, I would be happy to do that.
The glomeruli are tiny units that cleanse the blood in the
kidney and they are comprised of kidney membranes and small
capillary blood vessels. There are really two types of injuries
that occur. One is glomerulonephritis, which is caused by the
immune system. Many institutes at NIH work together to direct
attention to preventing kidney failure from glomerulonephritis.
The form that you are referring to, focal segmental
glomerulosclerosis, affects children, and as you implied in the
case of Alonzo Mourning, can affect African Americans
disproportionately. We have intensive research efforts together
with patient advocacy groups such as the NephCure Foundation.
In fact, we have launched a clinical trial directed at new and
more effective therapies for this important disorder, and we
are hopeful that from that trial, new, safer, and more
effective medication will emerge. But at the same time, we are
also reinforcing our basic research to understand the basis for
the injury that occurs in glomerulosclerosis.
Senator Specter. Thank you very much.
AGE-RELATED MACULAR DEGENERATION (AMD)
Dr. Sieving, with respect to macular degeneration, how are
you moving ahead on the clinical trial networks for advancing
AMD research?
Dr. Sieving. AMD is a leading cause of vision loss and, in
fact, one of the leading causes of disability in the elderly.
It is a neurodegenerative disease. A part of the mission of the
institute is to form alliances, scientific alliances and
communication related to other neurodegenerations, including
Parkinson's and Alzheimer's disease, because there are some
common features that mutually these two multiple areas can
learn.
Now, the AMD network specifically is going to tackle the
opportunities presented by existing and new compounds to modify
the effects of and the course of AMD. One such opportunity--it
is not actually a network, but one recent success came from the
finding reported about a year ago that antioxidant nutrients
and zinc can decrease the risk of progressing to end-stage
vision loss. That is a very important finding in the aggregate
for the American population. Now it is our task to take that
bedside finding back to the bench to help understand on a
molecular and cell biological basis why this is happening.
Back on the AMD networks, we are proceeding with that.
Applications are coming in, will be reviewed, and we hope that
we will be able to successfully fund this venture.
AUTISM RESEARCH
Senator Specter. Dr. Insel, with respect to autism, could
you bring us up to date on the research activities of your
department and what success you have had and what your
projection is for the future?
Dr. Insel. I would be happy to, Senator.
We have in the past year launched a total of eight STAART
centers. These are interdisciplinary centers to bring both a
research effort and an intervention effort to autism. This is a
program that will go over the next 4 to 5 years. It involves
five of the institutes that are here today. It is, we think, a
great national effort that will, by coordinating efforts across
many different sites, lead to some very new insights into this
troubling and still very mysterious illness.
Senator Specter. We have quite a number of questions for
the record. We very much appreciate your coming. We appreciate
even more the outstanding work you are doing. We are committed
to doing our utmost to help you on the funding. When the other
research entities come forward with their requests, it
continues to be my view that it is a very, very solid capital
investment for the United States and we will continue to push
on all lines.
Anything further, Senator?
SPINAL MUSCULAR ATROPHY (SMA)
Senator Harkin. Yes, just one thing, Mr. Chairman.
Dr. Landis, on the SMA issue and what you are sending up to
us, I tried to listen to your answer, but would you also look
ahead as to how soon we might be going to clinical trials, and
what the--I hate to use the word ``Roadmap'' but what that time
line might be?
Dr. Landis. We would be pleased to do that. The projection
is 4 years for this new initiative to come to fruition with
optimally selected compounds, but I will certainly give you a
detailed answer.
Senator Harkin. I will take a look at that.
TRANS-NIH OBESITY TASK FORCE
Back on the issue of obesity, I met with Dr. Gerberding
last week at CDC. They have said that now it may be surpassing
tobacco usage as the biggest health menace that we face as
Americans. Again, I am wondering how, Dr. Zerhouni, you are
approaching this in terms of NIH's role in looking at obesity.
Again, it always seems to me that it is easier for people
who have never been obese to not be obese than it is for
someone who becomes obese to lose weight and hold it down. That
is just the facts.
So how do we prevent it in the first place? It seems to me
that one of the links in child health, Dr. Alexander, as kids
develop and as they learn and grow--it seems to me some
research ought to be done on that, what hkids eat and how they
develop. And there may be some genetic problems too. I do not
know. Dr. Collins could be involved in that.
I guess what I am getting at is this seems to lend itself
to some kind of an inter-institute kind of task force to look
at how we get to the prevention end of it, not just to the
cure, but what are some of the forces that might go into
preventing this in the first place.
Dr. Zerhouni. You are absolutely correct, Senator. As I
indicated to you in the past through this graph, NIH started
investing in obesity 10 years ago. But more importantly is the
relevancy of the question you are asking. Last year I asked
that we form a trans-NIH Obesity Task Force that is led by Dr.
Spiegel. This year we are going to increase funding in obesity
research by 10 percent. Here on the screen I can actually show
you what that 10 percent is going to be related to [see figure
3]: $3.5 million will be the prevention and treatment of
childhood obesity in primary care settings; $3.5 million will
be site-specific approaches to prevent and treat pediatric
obesity.
In a nutshell, we are going to focus on the aspects of
prevention and understanding the evidence that we need to, in
fact, stop the leading edge of the epidemic which is, we agree,
in childhood. The earlier we intervene, the more likely we are
to dampen the epidemic as we see it. So we are focusing those
efforts exactly on that. We are widening our portfolio. We have
quadrupled our investment on obesity research because we knew
already a while back that it would become a public health
problem.
In addition to that, the other part of the new plan, which
is on the web site, is receiving public comment, which is
related to exactly what you are asking, this trans-NIH view,
the other end of the spectrum is most of the diseases that are
developed because of obesity are what we call comorbidities,
diabetes, hypertension. Those are the ones that really hit the
patients hard. Those do not occur to the same degree at every
level of overweight. They occur disproportionately in the very
morbid, high obesity patient with a BMI index of 33, 34, 35. So
the other component of our strategy is to look at the front
end, children, and look at those who are very likely to develop
the co-morbidities and understand how you stop obesity from
giving diabetes to patients and what is the relationship there,
what is the relationship with hypertension, and so on.
Dr. Spiegel, who is leading the trans-NIH task force, will
be happy to provide you more detailed information. But we agree
with you. It is a multi-prong strategy that we need to
implement across all Federal Departments and NIH needs to
attack now the leading edge and the trailing edge of what we
know are the most important points of action that we should
take.
Senator Harkin. Well, I appreciate it. From my own
standpoint, it is the leading edge is where you ought to focus.
I hope what I am not hearing, Mr. Chairman, is that somehow or
other we are going to do research into finding out how you can
be obese, but we can have some kind of blockers to keep you
from getting diabetes. I think more research ought to be into
the front end to keep you from getting obese in the first
place. That is my unscientific statement on that.
Thank you.
Dr. Zerhouni. Thank you, Senator.
Senator Specter. Thank you, Senator Harkin. Thank you all
very much.
PREPARED STATEMENT RECEIVED
We have received the prepared statement of Senator Mary L.
Landrieu which will be placed in the record.
[The statement follows:]
Prepared Statement of Senator Mary L. Landrieu
Thank you, Mr. Chairman. Thank you, Dr. Zerhouni, for joining us
today to discuss the National Institutes of Health (NIH) and its 2005
budget, as proposed by the President. The National Institutes of Health
are an integral component to our nation's health and safety. Within the
twenty-seven Institutes and Centers at the National Institutes of
Health, research is being conducted and studies are beginning to show,
new and exciting ways to prevent, detect, diagnose, and treat the
diseases and disabilities which plague our country and the world.
Fostering communication and collaboration, the National Institutes of
Health provide grant and research opportunities to universities,
medical schools, hospitals, and other research institutes in addition
to conducting their own federal research. Through these collaborations,
the National Institutes of Health position themselves as the world's
foremost medical research center and the focal point for domestic
medical research.
The President's fiscal year 2005 budget request provides $28.8
billion for the National Institutes of Health. This number represents
an increase of $764 million, or 2.7 percent, over fiscal year 2004
levels. As a member of the Senate Appropriations Subcommittee on Labor,
Health, Human Services and Education, I was proud to lend my support to
doubling the National Institutes of Health budget in just five years.
By steadfastly keeping the National Institutes of Health funding on
track, my colleagues and I enabled the National Institutes of Health to
support far more promising research than it was ever able to before,
and to advance into new areas of science. While I am very proud of this
aggressive increase and commitment to funding, we must not fall back on
our commitment to medical research.
Research at the National Institutes of Health has a real and direct
impact on my state of Louisiana. The Centers for Disease Control and
Prevention (CDC) reports that 9,306 people have been affected by the
West Nile Virus in the United States this year. 240 of those infected
have died. Of those cases, the state of Louisiana has reported 123
cases and 8 deaths this year. Mosquito-borne diseases, such as the West
Nile Virus, represent one of the most serious and preventable public
health threats for many states. With the recent outbreak of the West
Nile Virus in the United States, the National Institute of Allergy and
Infectious Diseases at the National Institutes of Health have
accelerated their research efforts into the West Nile Virus, possible
vaccines, and treatment options. We have not yet developed a vaccine to
combat the West Nile Virus but with the proper funding, researchers at
NIH are committed to finding one.
In addition to West Nile, Louisianians also find themselves
battling another deadly epidemic, obesity. Currently in the United
States there are 127 million adults that are overweight, 60 million of
whom are obese, and 9 million who are severely obese. For children ages
6-11, 30.3 percent are overweight and 15.3 percent are obese. These
numbers have more than doubled in the last thirty years. This epidemic
threatens the health of our Nation and increases the incidence of type
2 diabetes, fatty liver disease, kidney failure, as well as many other
diseases. I am pleased to learn that the fiscal year 2005 budget for
the National Institutes of Health supports an expansion of $40 million
to its obesity research portfolio but this is not nearly enough to
reverse a trend of this magnitude. I hope that we can do more in the
near future to end this epidemic. It is imperative that we work to
understand the neurobiological, genetic, behavioral, and environmental
basis of obesity and develop strategies to maintain healthy weight in
adults and children.
In conclusion, I would like to speak briefly about the flu epidemic
that has recently taken a toll on our country and the global community.
The CDC estimates that 10-20 percent of Americans come down with the
flu each year. Of these numbers, more than 100,000 people are
hospitalized and approximately 36,000 Americans die from the flu and
its complications each year. While we have not experienced a flu
pandemic since 1968, each fall and winter brings with it a new strain
of the flu. Research institutions and health departments around the
world are cooperating to track flu outbreaks and to determine the many
different types, strains, and causes. The National Institute of Allergy
and Infectious Diseases (NIAID) at NIH currently supports research into
how the flu virus works and into developing better vaccines to prevent
and treat the infection. By supporting this research at NIH we can hope
to better track the development of flu strains and arm ourselves with
the proper vaccines and treatments that will prevent deadly outbreaks.
While these are but a few examples of the impact of NIH research on
the state of Louisiana, I think they make it clear that the research
being funded through the National Institutes of Health has a real and
immediate impact on the citizens of our country. By wisely investing in
medical research that advances the prevention and treatment of
diseases, we in fact are saving money that would otherwise have to be
used to diagnose and treat these diseases. I know that my colleagues
agree that funding a cure is perhaps the best use of government
resources there is. It is my hope that we will continue to increase the
National Institutes of Health budget so that our children and
grandchildren can truly benefit from the cures and medical advances
made every day at NIH.
ADDITIONAL COMMITTEE QUESTIONS
Senator Specter. There will be some additional questions
which will be submitted for your response in the record.
[The following questions were not asked at the hearing, but
were submitted to the Department for response subsequent to the
hearing:]
Questions Submitted by Senator Herb Kohl
obesity
Question. Dr. Crawford, both USDA and FDA have recently announced
new efforts to combat the increasing problem of obesity. FDA announced
the ``Calories Count'' program, and USDA has money in several programs,
including WIC, to help battle this problem. However, for all of the
government's efforts, all of the money being put into this effort pales
in comparison to the food industry's billions of dollars worth of
advertising. How can the government successfully get its message out
when, at first glance, its efforts appear to be dwarfed by the food
industry? How do your agencies compete with that?
Answer. In support of the President's Healthier U.S. initiative,
the DHHS established a complementary initiative, Steps to a Healthier
U.S., which emphasizes personal responsibility for the choices
Americans make for healthy behaviors. One aspect of this initiative
focuses on reducing the major health burden created by obesity and
other chronic diseases. Following DHHS' July 2003 Roundtable on Obesity
and Nutrition, on August 11, 2003, FDA established an Obesity Working
Group, or OWG, to prepare a report that outlines an action plan to
cover critical dimensions of the obesity problem from FDA's perspective
and authorities. This report was released on March 12, 2004.
There is no simple answer to the problem of obesity. Achieving
success in reducing and avoiding obesity will occur only as a result of
efforts over time by individuals as well as various sectors of our
society. It should be noted, however, that most associations, agencies,
and organizations believe that diet and physical activity should be
addressed together in the fight against overweight and obesity.
The OWG report provides a range of short and long-term
recommendations to address the obesity epidemic with a focus on a
``calories count'' emphasis for FDA actions. These recommendations are
based on sound science and address multiple facets of the obesity
problem under FDA's purview, including developing appropriate and
effective consumer messages to aid consumers in making wiser dietary
choices; establishing educational strategies and partnerships to
support appropriate messages and teach people, particularly children,
how to lead healthier lives through better nutrition; developing
initiatives to improve the labeling of packaged foods with respect to
caloric and other nutrition information; encouraging and enlisting
restaurants in efforts to combat obesity and provide nutrition
information to consumers, including information on calories, at the
point-of-sale; developing new therapeutics for the treatment of
obesity; designing and conducting effective research in the fight
against obesity; and continuing to involve stakeholders in the process.
Regarding food labeling, the OWG report contains several
recommendations based on sound science. I will provide these
recommendations for the record.
[The information follows:]
Publish an advance notice of proposed rulemaking, or ANPRM, to seek
comment on the following:
--How to give more prominence to calories on the food label, for
example, increasing the font size for calories, including a
column in the Nutrition Facts panel of food labels for percent
Daily Value for total calories, and eliminating the listing for
calories from fat;
--Whether to authorize health claims on certain foods that meet FDA's
definition of ``reduced'' or ``low'' calorie. An example of a
health claim for a ``reduced'' or ``low'' calorie food might
be: ``Diets low in calories may reduce the risk of obesity,
which is associated with type 2 diabetes, heart disease, and
certain cancers.''
--Whether to require additional columns on the Nutrition Facts panel
to list quantitative amounts and percent Daily Value of an
entire package on those products and package sizes that can
reasonably be consumed at one eating occasion--or declare
quantitative amounts and percent Daily Value of the whole
package as a single serving if it can reasonably be consumed at
a single eating occasion; and,
--Which, if any, reference amounts customarily consumed of food
categories appear to have changed the most over the past decade
and hence require updating.
In addition, FDA will file and respond in a timely way to petitions
the agency has received that ask FDA to define terms such as ``low,''
``reduced,'' and ``free'' carbohydrate; and provide guidance for the
use of the term ``net'' in relation to carbohydrate content of food--
these petitions were filed on March 11, 2004.
FDA will also encourage manufacturers to use dietary guidance
statements, an example of which would be, ``To manage your weight,
balance the calories you eat with your physical activity.'' In
addition, the Agency will encourage manufacturers to take advantage of
the flexibility in current regulations on serving sizes to label as a
single-serving those food packages where the entire contents of the
package can reasonably be consumed at a single eating occasion and
encourage manufacturers to use appropriate comparative labeling
statements that make it easier for consumers to make healthy
substitutions.
FDA believes that if the report's recommendations are implemented
they will make a worthy contribution to confronting the nation's
obesity epidemic and helping consumers' lead healthier lives through
better nutrition.
FDA also believes that the regulatory scheme for claims in food
labeling, whether health claims, nutrient content claims, or other
types of claims, are science based, and we continue to consider
modifications to our regulations to keep up with recent scientific
developments. A benefit of standardized, science-based terminology, as
with other terms that FDA has defined that consumers may use to make
health-based dietary choices--e.g., terminology concerning fat
content--is that it allows consumers to compare across products and it
encourages manufacturers to compete based on the nutritional value of
the food. However, FDA does not regulate television and other media
marketing of food products. Some of the modifications FDA is currently
considering are described above in the list of topics to be covered by
the ANPRM the agency intends to issue.
With respect to conveying the report's messages to the public, FDA
believes that all parties, including the packaged food industry,
restaurants, academia, and other private and public sector
organizations in addition to government agencies at all levels, have an
essential role to play. On April 22, 2004, FDA's Science Board focused
on specific recommendations from the OWG report. These recommendations
call on FDA to work through a third-party facilitator to engage all
involved stakeholders in a dialogue on how best to construct and convey
obesity messages in the restaurant setting and in the area of pediatric
obesity education.
This approach is one example of how the Agency intends, by means of
public and private partnerships, to leverage its ability to convey
appropriate messages on obesity to the public with the goal of changing
behavior and ultimately reversing obesity trends in the United States.
IMPORT INSPECTIONS
Question. Dr. Crawford, the FDA budget this year includes a $7
million increase to fund 97,000 food import examinations. This is a big
increase in inspections over any previous year--still, however, less
than one percent of all of the food imported into this country will be
inspected. How would you respond to charges that you still aren't
inspecting nearly enough imported food, especially in light of events
during the past year where bad food has gotten in and people have died?
How do we ensure consumers that their food is indeed safe?
Answer. FDA is appreciative of the additional funding we have
received for the inspection of domestic firms and for inspections of
imported foods. FDA believes it is more effective to focus our
resources in a risk-based manner than to focus simply on increasing the
percentage of imported food shipments that are physically inspected. It
is important to note that every shipment of FDA-regulated food which is
entered through Customs and Border Protection as a consumption entry is
electronically reviewed by FDA's Operational and Administrative System
for Import Support to determine if it meets identified criteria for
further evaluation by FDA reviewers and physical examination and/or
sampling and analysis or refusal. This electronic screening allows FDA
to concentrate its limited inspection resources on high-risk shipments
while allowing low-risk shipments to proceed into commerce.
Due to constantly changing environments of operation, e.g.,
counterterrorism and BSE, our domestic inspection and import strategy
cannot be defined in terms of a percentage of coverage through
inspections, physical examinations and sample analyses. It needs to be
a flexible blend of the use of people, technology, information and
partnerships to help protect Americans from unsafe imported products.
Accordingly, the Agency is developing and using strategies for
mitigating risks prior to importation through partnerships and
initiatives based on best practices and other science based factors
relevant to the import life cycle, i.e., from foreign manufacturer to
the U.S. consumer. Recently this principle has been applied in the
``Canadian Facility Voluntary Best Management Practices for Expediting
Shipments of Canadian Grains, Oilseeds and Products to the United
States'' implemented February 24, 2004, and designed to mitigate the
potential of mammalian protein prohibited from being fed to cattle or
other ruminants under BSE-prevention regulations promulgated by CFIA
and FDA.
Another piece of the long term solution to a higher level of
confidence in the security and safety of food products lies in
information technology that will merge information on products and
producers with intelligence on anticipated risks to target products for
physical and laboratory examination or refusal. This strategy would
rely on data integrity activities that reduce the opportunity for
products to be incorrectly identified at ports. It would also rely on
cooperation from producers so that FDA can identify sources that are
unlikely to need physical testing. However, even with such targeting,
improvements are limited by the available methodologies for assessing
threat agents and our ability to predict which tests ought to be used.
We are ramping up our food inspections, but we recognize that we
also need to inspect smarter, not just inspect more. That is why FDA is
making significant investments in technology and information resources
such as the development of the Mission Accomplishment and Regulatory
Compliance Services System, MARCS. MARCS is a comprehensive redesign
and reengineering of two core mission critical systems at FDA: FACTS
and the Operational and Administrative System for Import Support,
OASIS. OASIS supports the review and decision making process of
products for which entry is sought into the United States. We are using
funds to work to further improve targeting and using force multipliers
such as IT.
FDA also has a proof of concept project, called ``Predict,'' with
New Mexico State University under a Department of Defencse contract
which is being designed to enhance agency capability to rapidly assess
and identify import entries based on risk using relevant information
from various sources including regulated industry, trade, other
federal, State, and local entities, and foreign industry and
governments. This project, if successful, will greatly enhance FDA's
capability to be smarter in directing field activities on products of
greater risk to public health and safety. The proof of concept project
is projected to be completed in the Fall of 2004. The relentless growth
in the volume of domestic as well as imported food products, which are
increasingly in ``ready for consumer sale packaging.'' Food imports are
now growing at 19 percent per year. FDA needs to use all the potential
tools available to improve its efficiency in food security and safety
coverage.
In addition, FDA has several strategic initiatives to enhance
safety. One of these is ``Agency Initiatives to Improve Coverage,''
which includes the creation of the Southwest Import District to better
coordinate import activities on the southern border. Another is
reciprocal FDA and U.S. Customs and Border Protection training to
improve product integrity of goods offered for import and increase
enforcement actions by Customs to deter willful violations of U.S. laws
and regulations. While foreign inspections and border operations
provide some assurance that imported foods are safe, the agency
continues to work to foster international agreements and harmonize
regulatory systems. For instance, we actively participate in the
Canada/U.S./Mexico Compliance Information Group, which shares
information on regulatory systems and the regulatory compliance status
of international firms to protect and promote human health.
It is very important that American consumers trust the safety of
the food supply. FDA has made fundamental changes in how we implement
our mission of protecting the food supply, so that all Americans can
have confidence that their food has been handled under secure
conditions that provide assurance of its safety.
FDA FOIA POLICIES
Question. Dr. Crawford, my office has been working with a non-
profit patient advocacy group, the TMJ Association, in their efforts to
have two FOIA requests that are well over a year old responded to.
Their original FOIA request was made on November 1, 2002 (request
number 02017071), more than 17 months ago, and the subsequent request
was made on March 25, 2003 (request number 03004361). They have not yet
received the information requested, and have been unable to get a date
commitment by FDA as to when the information will be provided. It is my
understanding that they have been informed that FOIA requests are
severely backlogged, and the FDA has no idea when they will be able to
process their request. What is the current backlog for FOIA requests?
Answer. As of April 28, 2004, FDA has 19,369 pending FOIA
requests--17,555 have been pending more than 20 days and 1,814 have
been pending 20 days or less. The Denver District Office is responsible
for responding to the two requests from the TMJ Association. As of
April 28, 2004, Denver District Office has 369 pending FOIA requests--
357 requests have been pending more than 20 days, and 12 requests have
been pending 20 days or less.
Question. How many FDA staff are responsible for handling these
requests? Is this their sole responsibility, or do they have other
responsibilities as well?
Answer. For fiscal year 2003 the total number of personnel
responsible for processing FOIA requests was 91 FTE, 75 full time
employees, and 16 FTE work years representing personnel with part-time
FOIA duties in addition to other responsibilities.
Question. Does FDA need additional staff or resources in order to
process these requests on a timely basis?
Answer. In some agency components FOIA is a collateral duty. For
example, in most FDA field offices, Compliance Officers whose primary
responsibilities are related to the Agency's regulatory enforcement
activities also perform FOIA duties as permitted by time and regulatory
workload. Additional staff devoted to FOIA could shorten the amount of
time for processing requests.
Question. What do you believe is a reasonable length of time for a
group to wait for an information request to be processed and responded
to?
Answer. Requests are processed by the agency component that
maintains the requested records. There are a number of factors that
must be considered in order to predict a reasonable amount of time for
a request to be processed. Those factors include the volume of requests
received by the component, the complexity of requests received, the
amount of time required to search for records, the amount of time
require to review the records to determine whether information is
releasable under FOIA, and the resources available to process requests.
Question. What is the average length of time it takes to process a
FOIA request? Can you please explain the severe delay in processing
this specific one, which has taken over two years and apparently has no
end in sight? Can you please provide me a timeframe within which the
FDA will respond to these two particular FOIA requests?
Answer. Under the Electronic Freedom of Act Amendments of 1996,
agencies are permitted to establish multiple tracks for processing FOIA
requests based on the complexity of the requests and the amount of work
and time required to process requests. Some FDA components have
established multiple processing tracks. Requests are processed on a
first in, first out basis within each track. The median number of days
to process requests in the simple processing track is 19 days. The
median number of days to process requests in the complex processing
track, for more complicated requests, is 363 days. For requests that
are not processed in multiple processing tracks, the median number of
days to process is 44 days.
Due to a heavy load of regulatory cases in the Denver District
Office that must be handled by the Compliance Officers in addition to
staff shortages, FOIA work in the Denver District is being performed by
one individual on a part-time basis. This has resulted in a significant
backlog of FOIA requests. The Denver District Office expects to fill
request 02-17071 from the TMJ Association in six months, and request
03-4361 in one month.
Question. What additional efforts can this group undertake in order
to speed up their request?
Answer. The Denver District Office expects to fill request 02-17071
from the TMJ Association in six months, and request 03-4361 in one
month.
In addition, the Denver District is reviewing and evaluating its
FOIA workload and will develop a strategy aimed at reducing the backlog
of FOIA requests.
Question. What is the FDA's policy on charging for FOIA requests
made by non-profit patient advocacy groups?
Answer. The FOIA sets forth criteria that agencies must follow with
respect to charging for processing FOIA requests. Non-profit
organizations are considered Category III requesters. Such requesters
receive 100 pages of duplication and two hours of search at no charge.
If the number of pages exceed 100 and/or if the amount of search time
exceeds two hours, Category III requesters are charged based on the
FOIA fee schedule of the Department of Health and Human Services. The
fee for duplication is $.10 per page, and the fee for search is based
on the grade level of the individual who processes the request. I will
be happy to provide the current grade rates for the record.
[The information follows:]
CURRENT GRADE RATES
GS-1 through 8--$18.00 per hour
GS-9 through 14--$36.00 per hour
GS-15 and above--$64.00 per hour
In addition, requesters may make a request for waiver or reduction
of fees if their request meets the following criteria: disclosure of
the information is in the public interest because it is likely to
contribute significantly to public understanding of the operations or
activities of the Government; and, disclosure is not primarily in the
commercial interest of the requester.
IMPLICIT PRE-EMPTION
Question. Adverse reactions to prescription drugs and other
medicines take the lives of more than 100,000 Americans each year, and
millions more are seriously injured. For many years, state tort laws
have enabled some victims to receive compensation for their injuries.
It has been brought to my attention that the Food and Drug
Administration (FDA) has stepped in to protect drug companies from
liability in some of these lawsuits, potentially robbing individuals of
their only means of compensation. FDA's actions are even more troubling
when you consider that these lawsuits have other important purposes,
such as deterring future bad behavior and providing the American public
with access to important health and safety information. How many times
has the FDA interfered in lawsuits, arguing that implicit pre-emption
prohibits a plaintiff from receiving compensation for their injuries?
In how many of these cases has a court held that the plaintiff's tort
claim was implicitly pre-empted by federal law?
Answer. In the past several years, the Department of Justice (DOJ)
has represented the United States in four cases involving state-law
challenges to the adequacy of FDA-approved risk information
disseminated for FDA-approved new drugs.\1\ In each case, DOJ contended
that the state-law claim was preempted by federal law. In addition, in
some cases, DOJ argued that the state-law claim was not properly before
the court by operation of the doctrine of primary jurisdiction.\2\
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\1\ FDA also periodically becomes involved, through the Department
of Justice, in cases involving preemption of state-law requirements
under the medical device provisions of the FDCA, which include an
express preemption provision, 21 U.S.C. 360k(a).
\2\ Primary jurisdiction allows a court to refer a matter to an
administrative agency for an initial determination where the matter
involves technical questions of fact and policy within the agency's
jurisdiction. See, e.g., Israel v. Baxter Labs., Inc., 466 F.2d 272,
283 (D.C. Cir. 1972); see also 21 CFR 10.60.
---------------------------------------------------------------------------
The legal basis for preemption in these cases is FDA's careful
control over drug safety, effectiveness, and labeling according to the
agency's comprehensive authority under the FDCA and FDA implementing
regulations. If state authorities, including judges and juries applying
state law, were permitted to reach conclusions about the safety and
effectiveness information disseminated with respect to drugs for which
FDA has already made a series of regulatory determinations based on its
considerable institutional expertise and statutory mandate, the federal
system for regulation of drugs would be disrupted. I will be happy to
include information on the four cases for the record.
[The information follows:]
Bernhardt
In 2000, two individual plaintiffs filed product liability actions
in a New York court against Pfizer, Inc., seeking a court order
requiring the company to send emergency notices to users of the
prescription antihypertensive drug CARDURA (doxazosin mesylate) and
their physicians. The notices would have described the results of a
study by a component of the National Institutes of Health (NIH) that,
the plaintiffs alleged, demonstrated that Cardura was less effective in
preventing heart failure than a widely used diuretic. FDA had not
invoked its authority to send ``Dear Doctor'' letters or otherwise
disseminate information regarding a drug that the agency has determined
creates an ``imminent danger to health or gross deception of the
consumer.'' (21 U.S.C. 375(b).) The plaintiffs, nevertheless, filed a
lawsuit under state common law seeking relief that, if awarded, would
have pressured the sponsor to disseminate risk information that FDA
itself had not disseminated pursuant to its statutory authority.
FDA's views were submitted to the federal district court in the
form of a Statement of Interest.\3\ The Statement relied on the
doctrine of primary jurisdiction. The Statement also took the position
that the plaintiffs' request for a court order requiring the
dissemination of information about NIH study results to users and
prescribers of CARDURA was impliedly preempted. According to the
Statement, the court order ``would frustrate the FDA's ability
effectively to regulate prescription drugs by having the Court
substitute its judgment for the FDA's scientific expertise.'' The
Statement also noted that, if the court granted the requested order, a
direct conflict would be created between the information required to be
disseminated by the court and the information required to be
disseminated by FDA under the FDCA (in the form of the FDA-approved
labeling).
---------------------------------------------------------------------------
\3\ Statement of Interest of the United States; Preliminary
Statement, Bernhardt v. Pfizer, Inc., Case No. 00 Civ. 4042 (LMM)
(S.D.N.Y. filed Nov. 13, 2000).
---------------------------------------------------------------------------
The Statement contended that state law could not provide a basis
for requiring a drug manufacturer to issue drug information that FDA
had authority to, but did not, require. Importantly, the submission did
not argue that the state-law claim was preempted because FDA had
reached a determination that directly conflicted with the plaintiff's
view. Nor did it assert that FDA had specifically determined that the
information on the NIH study requested by the plaintiffs was
unsubstantiated, false, or misleading. In this sense, the Statement of
Interest in Bernhardt was the most aggressive, from a legal
perspective, than the three subsequent DOJ submissions on FDA's behalf
in preemption cases made during the present Administration.
The United States District Court for the Southern District of New
York accepted the primary jurisdiction argument made on FDA's behalf.
(Bernhardt v. Pfizer, Inc., 2000 U.S. Dist. LEXIS 16963, *9 (whether
the additional warnings sought by the plaintiffs were appropriate ``is
a decision that has been squarely placed within the FDA's informed
expert discretion'')). It did not address the preemption issue. The
case was voluntarily dismissed on April 22, 2003.
Dowhal
In 1998, an individual plaintiff in California asked that State's
attorney general to initiate an enforcement action against SmithKline
Beecham and other firms marketing OTC nicotine replacement therapy
products in California. (These products are marketed pursuant to an
approved new drug application.) The plaintiff contended that the FDA-
approved warnings for the defendants' products did not meet the
requirements of a state statute called the Safe Drinking Water and
Toxic Enforcement Act (Cal. Health & Safety Code 25249.5 et seq.),
also known as Proposition 65. From 1996 through 2001, FDA had
repeatedly advised the defendants that they could be liable under the
FDCA for selling misbranded products if they deviated from the FDA-
approved warning labeling for their products. FDA also advised the
state attorney general in writing in 1998 that the defendants' warning
in the labeling clearly and accurately identified the risks associated
with the products and, therefore, met FDA requirements under the FDCA.
After receiving the letter, the attorney general declined to initiate
enforcement action.
Nevertheless, in 1999, the individual plaintiff initiated a lawsuit
of his own in California state court under Proposition 65's ``bounty-
hunter'' provision, which empowers individuals to file enforcement
actions under that statute on behalf of the people of the State of
California. The lawsuit asked the court to award civil money penalties
and restitution, and to issue an injunction requiring the defendants to
disseminate warnings for their products that differed from the warnings
required by FDA. In 2000, the plaintiff filed a citizen petition with
FDA requesting that the agency require the defendants to change their
warnings to reflect the language sought by the plaintiff in the
lawsuit. FDA rejected the proposed language, determining that it lacked
sufficient support in scientific evidence and presented a risk of
mischaracterizing the risk-benefit profile of the products in a way
that threatened the public health. Although the trial court found for
the defendant, the California Court of Appeal rejected the defendant's
contention that the plaintiff's claim was preempted under the FDCA, and
allowed the lawsuit to proceed. (Dowhal v. SmithKline Beecham Consumer
Healthcare, 2002 Cal. App. LEXIS 4384 (Cal. Ct. App. 2002), argued,
Case No. S-109306 (Cal. Feb. 9, 2004).)
FDA's views were presented to the Court of Appeal of California in
an amicus curiae (``friend of the court'') brief and to the Supreme
Court of California in a letter brief and an amicus brief.\4\ All three
documents explained that the warning language sought by the plaintiffs
had been specifically considered and rejected by FDA as scientifically
unsubstantiated and misleading. Including the language would,
therefore, misbrand those products and cause the defendants to violate
the FDCA. The documents explained, further, that principles of conflict
preemption applied to the plaintiffs' claim because it was impossible
for defendants to comply with both federal and state law and because
the state law posed an obstacle to the accomplishment of the full
purposes and objectives of the FDCA.
---------------------------------------------------------------------------
\4\ Letter from Robert D. McCallum, Jr., Ass't Attorney General, et
al., to Frederick K. Ohlrich, Supreme Court Clerk/Administrator, Dowhal
v. SmithKline Beecham Consumer Healthcare LP, et al., Case No. S-109306
(Cal. filed Sept. 12, 2002); Amicus Curiae Brief of the United States
of America in Support of Defendants/Respondents SmithKline Beecham
Consumer Healthcare LP, et al., Dowhal v. SmithKline Beecham, Case No.
A094460 (Cal. Ct. App. filed Mar. 22, 2002); Amicus Curiae Brief of the
United States of America in Support of Defendants/Appellants SmithKline
Beecham Consumer Healthcare LP, et al., Dowhal v. SmithKline Beecham,
Case No. S109306 (Cal. filed July 31, 2003).
---------------------------------------------------------------------------
The California Court of Appeal rejected the preemption argument.
(Dowhal v. SmithKline Beecham Consumer Healthcare, 2002 Cal. App. LEXIS
4384, ***16-17 (Cal. Ct. App. 2002) (reversing trial court decision
granting summary judgment for defendants on preemption grounds)). On
April 15, 2004, the California Supreme Court reversed the appeals court
decision, finding a direct conflict between FDA requirements and the
state-law warning requirement advocated by the plaintiff. (Dowhal v.
SmithKline Beecham Consumer Healthcare, 2004 Cal. LEXIS 3040.)
Motus
Also in 2000, an individual plaintiff sued Pfizer in a California
court alleging, among other things, that the company had failed to
fulfill its state common law duty to warn against the risk of suicide
the plaintiff alleged was presented by ZOLOFT (sertraline HCl), an FDA-
approved drug in the selective serotonin reuptake inhibitor (SSRI)
class indicated to treat depression (among other things). On numerous
occasions, FDA had specifically considered and rejected such language
for SSRIs as scientifically unsupportable and inconsistent with FDA
determinations as to the safety and effectiveness of the products.
The United States District Court for the Central District of
California (to which the case had been removed on the ground of
diversity) rejected the defendant's preemption argument, allowing the
lawsuit to proceed. (Motus v. Pfizer Inc., 127 F. Supp. 2d 1085 (C.D.
Cal. 2000).) The court later granted the defendant's motion for summary
judgment on non-preemption grounds (196 F. Supp. 2d 984, 986 (C.D. Cal.
2001)), and the plaintiff appealed. DOJ submitted an amicus curiae
brief to the United States Court of Appeals for the Ninth Circuit on
FDA's behalf.\5\ The brief's arguments were essentially the same as the
arguments advanced in Bernhardt. In contrast to the situation in
Bernhardt, however, in Motus, FDA had specifically considered, and
rejected, the language requested by the plaintiff under state law. The
appeals court affirmed the trial court's decision earlier this year
(2004 U.S. App. LEXIS 1944 (9th Cir. February 9, 2004)).
---------------------------------------------------------------------------
\5\ Amicus Brief for the United States in Support of the Defendant-
Appellee and Cross-Appellant, and in Favor of Reversal of the District
Court's Order Denying Partial Summary Judgment to Defendant-Appellee
and Cross-Appellant, Motus v. Pfizer, Case Nos. 02-55372 & 02-55498
(9th Cir. filed Sept. 3, 2002).
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In re PAXIL
In 2001, individuals filed suit in a California court on behalf of
past or current users of PAXIL (paroxetine HCl) against the drug's
manufacturer, GlaxoSmithKline (GSK), alleging that the company's
direct-to-consumer (DTC) broadcast advertisements for the drug failed
adequately to warn about the consequences of discontinuing the drug. In
reviewing the new drug application for the drug, FDA had found no
evidence that it was habit-forming and did not require GSK to address
that risk in FDA-approved labeling. FDA did, however, require GSK to
include in labeling statements regarding discontinuation syndrome, and
the labeling consequently recommends that doctors gradually reduce
dosages and monitor patients for syndrome symptoms. FDA reviewed
proposed DTC advertisements GSK had submitted for Paxil that said that
the drug was not habit-forming. The agency at no time determined that
this statement was misleading. In August 2002, notwithstanding FDA's
determination, the court issued a preliminary injunction prohibiting
GSK from running DTC advertisements stating that Paxil is not habit-
forming. (In re Paxil Litigation, 2002 U.S. Dist. LEXIS 16221 (C.D.
Cal. Aug. 16, 2002))
On reconsideration, the court declared that the preliminary
injunction challenged only ``FDA's . . . determination that the public
is not likely to equate the words not habit forming' as used in
direct[-]to[-]consumer advertisements with no withdrawal symptoms.'''
According to the court, ``The question of how members of the general
public are likely to interpret (or misinterpret) a statement is within
one of the courts' core competencies.'' Declaring itself ``unwilling to
blindly accept FDA's ultimate determination here,'' the court rejected
the defendants' preemption and primary jurisdiction arguments. It
nevertheless denied the injunction on the ground that the plaintiff was
not likely to succeed in demonstrating that ``non-habit forming''
statement in the advertisement is misleading. Thus, although the court
ultimately declined to award the injunctive relief sought by the
plaintiff, it continued to distinguish between FDA's determinations as
to the adequacy of drug warnings under federal law, and its own view of
warnings adequacy under state common law. (In re Paxil Litigation, 2002
U.S. Dist. LEXIS 24621 (C.D. Cal. Oct. 16, 2002).)
DOJ submitted to the court a Statement of Interest and a brief
asserting preemption.\6\ The Statement of Interest contended that a
court order requiring GSK to remove the ``non-habit-forming'' claim
from its advertisements for Paxil would be inconsistent with FDA's
determination that the company's advertisements were proper and that
Paxil is not, in fact, ``habit-forming.'' The brief contended that the
court should find the plaintiff's state-law request for a court order
preempted because it poses an obstacle to achievement of the full
objectives of Congress ``by attempting to substitute th[e] Court's
judgment for FDA's scientific expertise.'' As the brief pointed out,
FDA had specifically reviewed the advertisements, made suggestions
concerning the proper manner of presenting information relating to
whether Paxil is ``habit-forming,'' and, in the exercise of its
scientific and medical expertise, found the advertisements acceptable.
The brief also included a primary jurisdiction argument. The court
reversed its earlier award of an injunction prohibiting the
manufacturer from running advertisements that had been reviewed and
approved by FDA, but the reversal was based on a ground other than
preemption. (In re Paxil Litigation, 2002 U.S. Dist. LEXIS 24621 (C.D.
Cal. 2002).) \7\
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\6\ Statement of Interest of the United States of America, In re
PAXIL Litigation, Case No. CV 01-07937 MRP (CWx) (C.D. Cal. filed
August 20, 2002); Brief of the United States of America, In re PAXIL
Litigation, Case No. CV 01-07937 MRP (CWx) (C.D. Cal. filed Sept. 4,
2002).
\7\ In December 2003 (296 F. Supp. 2d 1374), the litigation,
consisting of twelve action in eleven federal judicial districts, was
centralized for pretrial proceedings in the United States District
Court for the Central District of California.
---------------------------------------------------------------------------
Conclusion
As these cases illustrate, courts entertaining lawsuits filed under
state law do not always defer to FDA on matters that Congress has
placed squarely within the agency's authority. In FDA regulatory areas
characterized by comprehensive regulation and requiring a careful and
expert evaluation of scientific data and public health issues, state
coregulation can stand as an obstacle to or directly conflict with the
agency's administration of its statutory mandate. Preemption is the
constitutionally prescribed mechanism for resolving these conflicts.
The practice of citing preemption and primary jurisdiction under
the FDCA in litigation in which the United States is not a party is
well-established and substantially predates the current Administration.
DOJ and FDA participation in these cases is unusual. In the current
Administration, DOJ has participated in private state-law actions on
FDA's behalf only following a judicial finding that the action should
proceed, and only to address a state-law finding that, left
undisturbed, would undermine FDA's execution of its statutory mission
or directly conflict with federal law. Responsibility for making final
decisions whether to make submissions in private lawsuits, on
preemption, primary jurisdiction, or any other issue, rests with the
Department of Justice--not FDA itself.
Question. These arguments conflict with long-standing FDA policy.
The law appears to contradict what the FDA has argued. What motivated
FDA to change its policy?
Answer. The Government's participation in cases arising under
state-law and presenting preemption issues is consistent with past FDA
practice and with the pertinent law.
The principal enabling statute of the Food and Drug Administration
is the Federal Food, Drug, and Cosmetic Act, FDCA. Under this statute,
FDA has broad authority to protect the public health by ensuring that
foods are safe, wholesome, sanitary, and properly labeled, and that
drugs and medical products are safe and effective. (See 21 U.S.C.
393(b)(2)(A)-(C).) By operation of the Supremacy Clause of the United
States Constitution (U.S. Const. Art. VI, clause 2), the FDCA nullifies
conflicting requirements established by the States in legislation,
regulations, or common law. (See Gibbons v. Ogden, 22 U.S. (9 Wheat.)
1, 211 (1824) (Marshall, C.J.).)
In the past, FDA has addressed conflicting state requirements in
the context of rulemaking. In 1982, for example, FDA promulgated
regulations requiring tamper-resistant packaging for over-the-counter
drugs. In the preamble accompanying the regulations, FDA stated its
intention that the regulations preempt any state or local requirements
that were ``not identical to . . . [the rule] in all respects.'' (47 FR
50442, 50447; Nov. 5, 1982.) Similarly, in 1986, FDA issued regulations
requiring aspirin manufacturers to include in labeling a warning
against use in treating chicken pox or flu symptoms in children due to
the risk of Reye's Syndrome. In the accompanying preamble, FDA said the
regulations preempted ``State and local packaging requirements that are
not identical to it with respect to OTC aspirin-containing products for
human use.'' (51 FR 8180, 8181; Mar. 7, 1986.) In 1994, FDA amended 21
CFR 20.63 to preempt state requirements for the disclosure of adverse
event-related information treated as confidential under FDA
regulations. (59 FR 3944; Jan. 27, 1994.)
In addition, for many years, conflicting state requirements have
been addressed by FDA through case-by-case participation in selected
lawsuits to which the United States has not been a party. Because FDA
lacks independent litigating authority, this participation has been by
the Department of Justice (DOJ) on FDA's behalf. The practice of
addressing conflicting state requirements through participation in
litigation dates back many years. For example, DOJ participated on
FDA's behalf in favor of preemption in both Jones v. Rath Packing
Company, 430 U.S. 519 (1977), and Grocery Manufacturers of America,
Inc. v. Gerace, 755 F.2d 993 (2d Cir. 1985). In addition, as discussed
in our response to the previous question on preemption, FDA has
recently participated in several cases involving state-law requirements
for the communication of risk information for prescription drugs. Of
note, the first--and most aggressive, from a legal perspective--of
these submissions occurred during the previous Administration--
Bernhardt case included in materials for the record.
NARMS
Question. What is the total amount of funding for NARMS, and from
what account does it come?
Answer. The total amount of funding for NARMS in fiscal year 2004
is $7.634 million. This funding is located in the Salaries and
Expenses, or S&E, account.
Question. How much is FDA giving to USDA and CDC in fiscal year
2005? How does that compare to fiscal year 2004? Please describe what
factors are used to determine the division of funds.
Answer. At this time, FDA has not determined the exact funding for
CDC and USDA for NARMS for fiscal year 2005 but plans to make decisions
by Fall 2004. In fiscal year 2004, FDA funding on NARMS will be reduced
due to government-wide rescissions. In fiscal year 2004, FDA provided
funds of approximately $1.6 million to USDA and $2 million to CDC. It
is important to point out that a large portion of the funds provided to
CDC is given to the states for the collection, isolation and
identification of bacterial isolates, which are then shipped to CDC and
the Food and Drug Administration's Center for Veterinary Medicine--
NARMS retail arm--for susceptibility testing. In determining the funds
provided to CDC and USDA, we analyze the entire NARMS program,
including the retail food arm of NARMS, and strive to fill in data gaps
and avoid duplication of organisms to be tested.
Question. How much NARMS money is currently being spent in foreign
countries, specifically Mexico? How is this money being used?
Answer. FDA is not spending any current year NARMS funding in
Mexico or other foreign countries.
Question. Does USDA or CDC spend any of their NARMS money in
foreign countries?
Answer. In fiscal year 2004 FDA is providing USDA and CDC, $1.6
million and $2 million respectively. FDA does not keep detailed records
of USDA and CDC funding for NARMS.
COUNTERFEIT DRUGS
Question. In February, FDA released a report on combating
counterfeit drugs. Several new technologies were mentioned that could
be used to this effect, including Radiofrequency Identification
tagging, color shifting inks, and holograms. Specifically regarding
color shifting inks, which I understand are currently available, has
FDA taken any action, or do you have any plans to pursue this option?
Answer. It is true that color shifting ink technology is currently
available for use on drug packaging and labeling. However, we heard
uniformly from all stakeholders that this technology is expensive and
requires significant investment of resources and time prior to
implementation. Due to the wide variety of products, packaging, and
labeling on the market, we heard from manufacturers, wholesalers, and
retailers that the decision to use color shifting inks, or any other
authentication technology, should be made by the manufacturer after a
manufacturer initiated product risk assessment. Without such an
analysis, use of color-shifting ink, or other authentication
technology, could lead to an unnecessary increase in the cost of drugs
to consumers. For example, we heard that color-shifting ink could be
appropriate for use on a very expensive, high volume brand name drug
product that is likely to be counterfeited, but not on a generic or low
volume drug product that is less likely to be counterfeited.
Based on our discussions with manufacturers, we estimate that it
would take a minimum of six to twelve months to implement a technology
such as color shifting ink from the time a decision is made to use the
authentication technology on the packaging and/or labeling of a drug
product. It could take longer if the technology, e.g., color-shifting
ink, is used on the product itself because safety studies might have to
be performed to ensure that the technology, e.g., the ink, does not
affect the safety or stability of the product.
ANIMAL DRUG COMPOUNDING
Question. Dr. Crawford, on February 10, I submitted a letter to Dr.
McClellan regarding FDA's new Compliance Policy Guidelines, issued July
14, 2003, regarding animal drug compounding. I received a response from
FDA on March 31st, and I thank you for that. However, I do have a few
more questions in light of the response.
First, the letter stated that FDA issued the CPG for immediate
implementation because of the ``urgent need to explain how it intended
to exercise its enforcement discretion regarding compounded drugs for
animal use in light of Thompson v. Western States Medical Center.''
However, this case dealt only with compounding in human drugs, not
animal drugs. How does this create an urgent need to deal with animal
drugs?
Answer. After the Western States decision, FDA revised its
enforcement policy on pharmacy compounding of human drugs. FDA was
concerned that without updated guidance regarding compounding of animal
drugs, the public would remain uncertain about whether and how FDA
would change its enforcement policy with respect to compounded animal
drugs. In addition, agency staff would lack clear guidance on
enforcement matters.
As FDA stated in its letter, although prior public comment was not
sought in this case, pursuant to the good guidance practices
regulations the public was invited to comment on the CPG when it was
issued and may comment on it at any time (68 FR 41591 (July 14, 2003)).
FDA has been reviewing those comments and will revise the guidance as
appropriate upon completion of our review.
Question. Second, the response states that two federal appeals
court decisions have held that ``the Federal Drug & Cosmetic Act does
not permit veterinarians to compound unapproved finished drugs from
bulk substances, unless the finished drug is not a new animal drug.
These cases support FDA's position that new animal drugs that are
compounded from bulk substances are adulterated under the FD&C Act and
may be subject to regulatory action.'' I have been informed that the
cases cited deal only with veterinarians compounding drugs, not
pharmacists. Why do you limit pharmacists as well as veterinarians? Is
this supported by any congressionally-enacted statutory authority,
legislative history or case law?
Answer. The principle established by the courts applies equally to
compounding by pharmacists and veterinarians.
Veterinary medicine has not traditionally utilized the services of
compounding pharmacies to the extent that they have been utilized
within human medicine. The increasing activities and presence of
compounding pharmacies in veterinary medicine is a relatively recent
development.
The Federal Food Drug and Cosmetic Act, or ``the Act'', and its
implementing regulations do not exempt veterinarians or pharmacists
from the approval requirements in the new animal drug provisions of the
Act, 21 U.S.C. Section 360b. In the absence of an approved new animal
drug application, the compounding of a new animal drug from any
unapproved drug or from bulk drug substances results in an adulterated
new animal drug within the meaning of section 21 U.S.C. Section
351(a)(5). The compounding of a new animal drug from an approved human
or animal drug also results in an adulterated new animal drug within
the meaning of 21 U.S.C. Section 351(a)(5), unless the conditions set
forth in 21 CFR 530.13(b) relating to extralable use are met.
FDA is concerned about veterinarians and pharmacists that are
engaged in manufacturing and distributing unapproved new animal drugs
in a manner that is clearly outside the bounds of traditional pharmacy
practice and that violates the Act--such as compounding that is
intended to circumvent the drug approval process and provide for the
mass marketing of products that have been produced with little or no
quality control or manufacturing standards to ensure the purity,
potency, and stability of the product.
Pharmacists and veterinarians who engage in activities analogous to
manufacturing and distributing drugs for use in animals may be held to
the same provisions of the Act as manufacturers.
Question. Finally, the final paragraph of the FDA response states
``Accordingly, the regulations that implement AMDUCA provide that
extralabel use by compounding applies only to compounding of a product
from approved drugs, and that nothing in the regulations is to be
construed as permitting compounding from bulk drugs.'' Is there in the
agency's view anything in AMDUCA's regulations or the Act that is to be
construed as not permitting compounding from bulk substances?
Answer. As previously noted, under the Federal Food, Drug and
Cosmetic Act, in the absence of an approved new animal drug
application, the compounding of a new animal drug from a bulk substance
results in a new animal drug that is adulterated as a matter of law.
This has been FDA's longstanding position, which is supported by two
federal appeals court decisions, United States v. Algon Chemical Inc.,
879 F.2d 1154 (3d Cir. 1989) and United States v. 9/1 Kg. Containers,
854 F.2d 173 (7th Cir. 1988).
CONCLUSION OF HEARINGS
Senator Specter. Thank you all very much for being here.
That concludes our hearings.
[Whereupon, at 10:48 a.m., Thursday, April 1, the hearings
were concluded, and the subcommittee was recessed, to reconvene
subject to the call of the Chair.]