[House Hearing, 114 Congress]
[From the U.S. Government Publishing Office]
THE SCIENCE AND ETHICS OF
GENETICALLY ENGINEERED HUMAN DNA
=======================================================================
HEARING
BEFORE THE
SUBCOMMITTEE ON RESEARCH & TECHNOLOGY
COMMITTEE ON SCIENCE, SPACE, AND TECHNOLOGY
HOUSE OF REPRESENTATIVES
ONE HUNDRED FOURTEENTH CONGRESS
FIRST SESSION
__________
JUNE 16, 2015
__________
Serial No. 114-24
__________
Printed for the use of the Committee on Science, Space, and Technology
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Available via the World Wide Web: http://science.house.gov
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COMMITTEE ON SCIENCE, SPACE, AND TECHNOLOGY
HON. LAMAR S. SMITH, Texas, Chair
FRANK D. LUCAS, Oklahoma EDDIE BERNICE JOHNSON, Texas
F. JAMES SENSENBRENNER, JR., ZOE LOFGREN, California
Wisconsin DANIEL LIPINSKI, Illinois
DANA ROHRABACHER, California DONNA F. EDWARDS, Maryland
RANDY NEUGEBAUER, Texas SUZANNE BONAMICI, Oregon
MICHAEL T. McCAUL, Texas ERIC SWALWELL, California
MO BROOKS, Alabama ALAN GRAYSON, Florida
RANDY HULTGREN, Illinois AMI BERA, California
BILL POSEY, Florida ELIZABETH H. ESTY, Connecticut
THOMAS MASSIE, Kentucky MARC A. VEASEY, TEXAS
JIM BRIDENSTINE, Oklahoma KATHERINE M. CLARK, Massachusetts
RANDY K. WEBER, Texas DON S. BEYER, JR., Virginia
BILL JOHNSON, Ohio ED PERLMUTTER, Colorado
JOHN R. MOOLENAAR, Michigan PAUL TONKO, New York
STEVE KNIGHT, California MARK TAKANO, California
BRIAN BABIN, Texas BILL FOSTER, Illinois
BRUCE WESTERMAN, Arkansas
BARBARA COMSTOCK, Virginia
DAN NEWHOUSE, Washington
GARY PALMER, Alabama
BARRY LOUDERMILK, Georgia
RALPH LEE ABRAHAM, Louisiana
------
Subcommittee on Research and Technology
HON. BARBARA COMSTOCK, Virginia, Chair
FRANK D. LUCAS, Oklahoma DANIEL LIPINSKI, Illinois
MICHAEL T. MCCAUL, Texas ELIZABETH H. ESTY, Connecticut
RANDY HULTGREN, Illinois KATHERINE M. CLARK, Massachusetts
JOHN R. MOOLENAAR, Michigan PAUL TONKO, New York
BRUCE WESTERMAN, Arkansas SUZANNE BONAMICI, Oregon
DAN NEWHOUSE, Washington ERIC SWALWELL, California
GARY PALMER, Alabama EDDIE BERNICE JOHNSON, Texas
RALPH LEE ABRAHAM, Louisiana
LAMAR S. SMITH, Texas
C O N T E N T S
June 16, 2015
Page
Witness List..................................................... 2
Hearing Charter.................................................. 3
Opening Statements
Statement by Representative Barbara Comstock, Chairwoman,
Subcommittee on Research, Committee on Science, Space, and
Technology, U.S. House of Representatives...................... 5
Written Statement............................................ 5
Statement by Representative Daniel Lipinski, Ranking Minority
Member, Subcommittee on Research, Committee on Science, Space,
and Technology, U.S. House of Representatives.................. 6
Written Statement............................................ 7
Statement by Representative Lamar S. Smith, Chairman, Committee
on Science, Space, and Technology, U.S. House of
Representatives................................................ 8
Written Statement............................................ 9
Witnesses:
Dr. Victor J. Dzau, President, Institute of Medicine, the
National Academy of Sciences
Oral Statement............................................... 10
Written Statement............................................ 13
Dr. Jennifer Doudna, Professor of Biochemistry and Molecular
Biology, University of California,
Oral Statement............................................... 18
Written Statement............................................ 20
Dr. Elizabeth McNally, Professor of Genetic Medicine, Professor
in Medicine-Cardiology and Biochemistry and Molecular Genetics;
Director, Center for Genetic Medicine, Northwestern University
Oral Statement............................................... 23
Written Statement............................................ 25
Dr. Jeffrey Kahn, Professor of Bioethics and Public Policy;
Deputy Director for Policy and Administration, Berman Institute
of Bioethics, Johns Hopkins University
Oral Statement............................................... 32
Written Statement............................................ 34
Discussion....................................................... 40
Appendix I: Answers to Post-Hearing Questions
Dr. Elizabeth McNally, Professor of Genetic Medicine, Professor
in Medicine-Cardiology and Biochemistry and Molecular Genetics;
Director, Center for Genetic Medicine, Northwestern University. 64
Appendix II: Additional Material for the Record
Statement by Representative Eddie Bernice Johnson, Ranking
Member, Committee on Science, Space, and Technology, U.S. House
of Representatives............................................. 66
THE SCIENCE AND ETHICS OF
GENETICALLY ENGINEERED HUMAN DNA
----------
TUESDAY, JUNE 16, 2015
House of Representatives,
Subcommittee on Research and Technology
Committee on Science, Space, and Technology,
Washington, D.C.
The Subcommittee met, pursuant to call, at 2:16 p.m., in
Room 2318 of the Rayburn House Office Building, Hon. Barbara
Comstock [Chairwoman of the Subcommittee] presiding.
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Chairwoman Comstock. The Subcommittee on Research and
Technology will come to order. Without objection, the Chair is
authorized to declare recesses of the Subcommittee at any time.
And without objection, the gentleman from California, Mr.
Sherman, is authorized to participate in today's hearing.
Good afternoon, and welcome to this hearing entitled ``The
Science and Ethics of Genetically Engineered Human DNA.''
And I believe we also would like to welcome Representative
Abraham to his first Science Committee hearing. Dr. Abraham, we
are happy to have you join the Research and Technology
Subcommittee and we look forward to having the benefit of your
expertise.
Now, in front of you are packets containing the written
testimonies, biographies, and truth-in-testimony disclosures
for today's witnesses.
I now recognize myself for an opening statement.
Biotechnology--the engineering of genetic material in
living beings and plants--has transformed modern medicine and
agriculture. Rapid advances in biotech research have brought
great opportunities for new medical treatments and products,
and simultaneously have also raised questions about possible
ethical implications and safety issues.
Today, we are here to discuss the science and ethics of the
most recent and eye-opening development in biotechnology: human
genome-editing. This research has been a major topic of news
and editorials in recent months. New tools that allow a gene to
be deleted, inserted, or replaced by a different piece of DNA
are becoming more cost-effective and simpler to execute.
In April it was reported that for the first time a team of
Chinese scientists had attempted to edit the genome of human
embryos. The report raised concerns for many scientists and
policymakers about the safety and ethics of using these new
technologies on human DNA. Many prominent scientists have
called for a better framework to be developed for responsible
use of the technology.
I look forward to learning more from our witnesses today
who will provide an overview of the science behind these new
technologies, help us examine the implications and risks, and
explore what the next steps should be for building the right
kind of framework for utilizing the technology. They will also
help us answer how the United States can be a leader and
provide scientific and ethical leadership in this arena.
[The prepared statement of Chairwoman Comstock follows:]
Prepared Statement of Subcommittee
Chairwoman Barbara Comstock
Biotechnology--the engineering of genetic material in living beings
and plants--has transformed modern medicine and agriculture.
Rapid advances in biotech research have brought great opportunities
for new medical treatments and products, and simultaneously have also
raised questions about possible ethical implications and safety issues.
Today, we are here to discuss the science and ethics of the most
recent and eye-opening development in biotechnology: human genome-
editing.
This research has been a major topic of news and editorials in
recent months. New tools that allow a gene to be deleted, inserted, or
replaced by a different piece of DNA are becoming more cost-effective
and simpler to execute.
In April, it was reported that for the first time a team of Chinese
scientists had attempted to edit the genome of human embryos. The
report raised concerns for many scientists and policy makers about the
safety and ethics of using these new technologies on human DNA.
Many prominent scientists have called for a better framework to be
developed for responsible use of the technology.
I look forward to learning more from our witnesses today who will
provide an overview of the science behind these new technologies, help
us examine the ethical implications and risks, and explore what the
next steps should be for building a responsible framework for utilizing
the technology. They will also help us answer how the United States can
provide scientific and ethical leadership in this arena.
Chairwoman Comstock. So I now recognize the Ranking Member,
the gentleman from Illinois, for his opening statement.
Mr. Lipinski. Thank you, Chairwoman Comstock, for holding
this hearing on the science and ethics of new gene editing
technologies.
I want to thank all the witnesses for being here today and
look forward to your testimony.
Although we're talking about gene editing technologies that
are very new, it's important to mention that humans have been
altering the genomes of species through selective breeding for
thousands of years. And since the 1970s, it has been possible
to directly manipulate DNA, which led to a biotechnology
revolution and significant economic growth.
Then we had the Human Genome Project to sequence the human
genome, and it was coordinated by the Department of Energy and
the National Institutes of Health. The full human genome was
sequenced in 2003, opening up whole new possibilities for
diagnosing and treating diseases. One such pathway led to the
invention of the CRISPR technology.
Thanks to new gene editing technologies, which include
CRISPR, we're able to add, remove, and replace DNA bases. They
can be thought of as search-and-replace tools for DNA. They're
incredibly powerful technologies that have the potential to
transform the healthcare, energy, and agricultural sectors.
Although new, these technologies were the outgrowth of decades
of fundamental research, some of which was supported by the
National Science Foundation.
We are here today because a Chinese research group recently
published a paper in which they used these technologies to try
to modify human embryos. That paper highlights scientific and
ethical issues with these technologies, especially if they are
being used to modify human germline cells as opposed to adult
somatic cells.
I look forward to hearing about the science behind these
technologies, as well as how the United States can be a leader
in addressing the safety and ethical concerns associated with
them.
I understand the National Academies has launched a major
initiative around human gene editing technologies. In the
1970s, the National Academies played a similar role dealing
with the then-new biotechnologies, and I look forward to
hearing more about what they're planning to do concerning these
new gene editing technologies. I also look forward to hearing
about some of the potential nonhuman applications.
[The prepared statement of Mr. Lipinski follows:]
Prepared Statement of Subcommittee
Minority Ranking Member Daniel Lipinski
Thank you Chairwoman Comstock for holding this hearing on the
science and ethics of new gene editing technologies. I want to thank
all the witnesses for being here this afternoon and I look forward to
hearing your testimony.
Although we are talking about gene editing technologies that are
very new, it is important to mention that humans have been altering the
genomes of species through selective breeding for thousands of years.
Since the 1970s, it has been possible to directly manipulate DNA, which
led to a biotechnology revolution and significant economic growth. Then
we had the Human Genome Project to sequence the human genome that was
coordinated by the Department of Energy and the National Institutes of
Health. The full human genome was sequenced in 2003, opening up whole
new possibilities for diagnosing and treating diseases. One such
pathway led to the invention of the CRISPR technology.
Thanks to new gene editing technologies, which include CRISPR, we
are able to add, remove, and replace DNA bases. They can be thought of
as ``search and replace'' tools for DNA. They are incredibly powerful
technologies that have the potential to transform the health care,
energy, and agricultural sectors. Although new, these technologies were
the outgrowth of decades of fundamental research, some of which was
supported by the National Science Foundation. We are here today because
a Chinese research group recently published a paper in which they used
these technologies to try to modify human embryos. That paper
highlights scientific and ethical issues with these technologies,
especially if they are being used to modify human germline cells as
opposed to adult somatic cells.
I look forward to hearing about the science behind these
technologies as well as how the United States can be a leader in
addressing the safety and ethical concerns associated with them. I
understand that the National Academies has launched a major initiative
around human gene editing technologies. In the 1970s, the National
Academies played a similar role dealing with the then-new
biotechnologies and I look forward to hearing more about what they are
planning to do concerning these new gene editing technologies. I also
look forward to hearing about some of the potential non-human
applications.
Now I would like to yield my remaining time to my colleague from
Illinois, Mr. Foster, who is very interested in this topic and helped
organize today's hearing.
Mr. Lipinski. With that, I'd like to yield my remaining
time to my colleague and neighbor from Illinois, Dr. Foster,
who was very interested in this topic and helped to organize
today's hearing.
Mr. Foster. Thank you, and I'd like to thank the whole
Research and Technology Subcommittee, including the Chair,
Congresswoman Comstock, and Ranking Member Lipinski for
allowing me to join you here today. And similarly, I wanted to
thank Chairman Smith and Ranking Member Johnson for agreeing to
hold this hearing. And a very special thank you to the
witnesses for taking their time out for this very important
issue.
It is rare that prominent members of the scientific
community come together to warn our leaders of technological
breakthroughs that our legal system and society may not be
prepared for, and yet, this is exactly what appears to be
happening with recent discoveries in genetic editing tools.
As the last Ph.D. scientist in Congress, I am afraid I've
served a sort of a lightning rod for many of these warnings and
I take them very seriously.
I want to commend the National Academy of Sciences and the
Institute of Medicine for the launch of their major initiative
on human gene editing, and I want to make sure that Congress
does everything constructive that it can to make sure that this
is handled responsibly.
There is the possibility of very great benefits from these
new technologies, and what makes them really revolutionary is
what they can mean for humans, for example, replacing bone
marrow of someone suffering from sickle cell disease with a
modified version of their own marrow with the genetic defect
removed.
However, if genetic modifications are made to so-called
germline cells--these are sperm, eggs, embryos--then the
modifications will be carried forward to future generations,
which has implications that we need to carefully consider.
We're on the verge of a technological breakthrough that could
change the future of mankind and we must not blindly charge
ahead.
Thank you, and I yield back my time.
Mr. Lipinski. I will just conclude. I agree with Dr. Foster
and it's great to see that we have so many people here at this
hearing. And it's a very important issue that we really need to
consider deeply, so I thank the Chairwoman and the Chairman of
the Full Committee, Chairman Smith, for holding this hearing
today, and I'll yield back.
Chairwoman Comstock. Thank you.
And I now recognize the Chairman of the Full Committee, Mr.
Smith.
Chairman Smith. Thank you, Madam Chair.
I do look forward, as do the others, to today's discussion
on a new development in biology, which has been called ``a game
changer,'' ``revolutionary,'' ``powerful,'' and ``a major issue
for all humanity.''
The new discoveries in genetically engineering human DNA
offer potential cures for devastating genetic disorders. But
the speed at which these new, simpler, and cheaper technologies
are being used in the lab also presents ethical and health
concerns. Most of the scientific community members have been
clear: the science and ethics of this new technology must be
resolved in order to prevent dangerous abuses and unintended
consequences.
A recent report from China, where teams of researchers have
begun to experiment with engineering DNA in human embryos, is
alarming. This is an area where the United States can and
should provide scientific and moral leadership. We need to
better understand the technology and procedures being used so
that we can ensure patients are treated in the safest and most
ethical manner possible.
An April editorial in Science magazine called for a prudent
path forward for genomic engineering. It recommended a
moratorium on further research, while creating public forums
for scientists, ethicists, and policymakers to discover the--to
discuss ``the attendant ethical, social, and legal implications
of genome modification.'' This is why it is important that the
House Science Committee is holding the first Congressional
hearing on this profound and complex subject.
The purpose of the Science Committee is to explore the
significance of scientific discoveries, as well as their
potential implications for humankind. But we also must always
be conscious of the potential ethical and moral issues raised
by previously unimagined scientific breakthroughs. We must take
the lead in reviewing new and innovative areas of science, such
as genetically engineered DNA.
So I look forward, Madam Chair, to this informative
discussion today, and we have an excellent panel of witnesses
to hear from as well.
And I'll yield back.
[The prepared statement of Chairman Smith follows:]
Prepared Statement of Committee on Science, Space, and Technology
Chairman Lamar Smith
Thank you Madam Chair. I look forward to today's discussion on a
new development in biology, which has been called ``a game changer,''
``revolutionary,'' ``powerful,'' and ``a major issue for all
humanity.''
The new discoveries in genetically engineering human DNA offer
potential cures for devastating genetic disorders. But the speed at
which these new, simpler and cheaper technologies are being used in the
lab also presents ethical and health concerns.
Most of the scientific community members have been clear: the
science and ethics of this new technology must be resolved in order to
prevent dangerous abuses and unintended consequences.
A recent report from China, where teams of researchers have begun
to experiment with engineering DNA in human embryos, is alarming. This
is an area where the United States can and should provide scientific
and moral leadership.
We need to better understand the technology and procedures being
used so that we can ensure patients are treated in the safest and most
ethical manner possible.
An April editorial in Science Magazine called for a prudent path
forward for genomic engineering. It recommended a moratorium on further
research, while creating public forums for scientists, ethicists and
policy makers to discuss ``the attendant ethical, social, and legal
implications of genome modification.''
This is why it is important that the House Science Committee is
holding the first congressional hearing on this profound and complex
subject.
The purpose of the Science Committee is to explore the significance
of scientific discoveries as well as their potential implications for
humankind.
But we also must always be conscious of the potential ethical and
moral issues raised by previously unimagined scientific breakthroughs.
We must take the lead in reviewing new and innovative areas of
science, such as genetically engineered DNA.
I look forward to an informative discussion with our distinguished
panel of witnesses.
Chairwoman Comstock. Thank you.
And if there are Members who wish to submit additional
opening statements, your statements will be added to the record
at this point.
Now, at this time I would like to introduce our witnesses.
Dr. Victor Dzau is the President of the National Academies
Institute of Medicine and the James B. Duke Professor of
Medicine at Duke University. Dr. Dzau has received many honors,
including the Distinguished Scientist Award from the American
Heart Association. He earned his undergraduate and medical
degrees from McGill University and holds eight honorary
doctorates.
Our second witness today is Dr. Jennifer Doudna. I think I
got that. Dr. Doudna is Professor of Molecular and Cell Biology
and Professor of Chemistry at U.C. Berkeley. A member of the
National Academy of Sciences, Dr. Doudna is the recipient of
several awards, including the NSF Waterman Award and the 2015
Breakthrough Prize for Life Sciences. Dr. Doudna earned her
undergraduate degree in biochemistry from Pomona College and
her Ph.D. in biological chemistry from Harvard University.
I now recognize the gentleman from Illinois, Mr. Lipinski,
to introduce our next witness.
Mr. Lipinski. Thank you.
As a Northwestern University alumnus, I'm very excited to
have Dr. McNally here today. To say an aside, Dr. Dzau, I'm
also an alum of Duke University, and unfortunately for Dr.
Doudna, an alum of Stanford also.
Dr. McNally is the Director of the Center for Genetic
Medicine and Professor in the Departments of Medicine and
Biochemistry at Northwestern University's Feinberg School of
Medicine. She is a cardiologist who specializes in inherited
forms of heart disease. Dr. McNally's research has identified
genes and mechanisms for how genetic lead to heart and muscle
disease. She has an undergraduate degree in biology and
philosophy from Barnard College at Columbia University and an
M.D. and Ph.D. from the Albert Einstein College of Medicine.
It is my pleasure to welcome Dr. McNally to our committee
and look forward to her testimony.
Chairwoman Comstock. Okay. And our final witness is Dr.
Jeffrey Kahn, the Robert Henry Levi and Ryda Hecht Levi
Professor of Bioethics and Public Policy at the Johns Hopkins
Berman Institute of Bioethics and a Professor in the Department
of Health Policy and Management at the Johns Hopkins Bloomberg
School of Public Health. Dr. Khan received his bachelor's in
microbiology from the University of California, Los Angeles,
his master's in public health from Johns Hopkins, and his Ph.D.
in philosophy and bioethics from Georgetown University.
In order to allow time for discussion, we would ask that
you limit your testimony to five minutes and your entire
written statement will be made part of the record.
I now recognize Dr. Dzau for five minutes to present his
testimony.
TESTIMONY OF DR. VICTOR J. DZAU, PRESIDENT,
INSTITUTE OF MEDICINE,
THE NATIONAL ACADEMY OF SCIENCES
Dr. Dzau. Good afternoon, Chairman Smith, Chairwoman
Comstock, Ranking Member Lipinski, and Subcommittee Members. As
you heard, I'm Victor Dzau. I'm the President of the Institute
of Medicine, which will soon be named the National Academy of
Medicine on July 1.
I'm pleased to be here on behalf of the National Academies
of Sciences, Engineering, and Medicine. The Academies operate
under a Congressional Charter signed by Abraham Lincoln to
provide advice to the Nation on matters where science,
technology, and medicine can solve complex challenges and
thereby improve people's lives.
Thank you for the opportunity to speak with you today about
this very important matter of human gene editing and the major
initiative that we have at the National Academies launched to
help guide decision-making in this area.
The Academies have an established record of leadership on
advising on emerging and often controversial areas of science,
particularly genetic research, such as recombinant DNA and stem
cell research. Our initiative is marshaling the best scientific
evidence, medical, ethical, legal, and other expertise to help
you and the Nation obtain a thorough understanding of gene
editing and its potential risks and benefits. Our work is
intended to provide a solid foundation to help inform decisions
and policies on this research.
As you will hear from other witnesses today, gene editing
technology holds great promise. In fact, powerful new tools
such as CRISPR/Cas9 developed by my colleague Dr. Doudna and
others, as well as other genetic engineering technology, allow
researchers now to precisely modify the genetic makeup of any
living organism, including humans. The possible benefit
application for such technologies are many. They could offer a
cure to devastating genetic diseases such as Huntington's
disease, as you heard, or sickle cell anemia. It can help
improve and understand the treatment of many other illnesses.
These technologies also present complex challenges both to
scientific and medical communities and to society as a whole.
Of particular concern is the potential to make permanent
modification to human DNA in nuclei of eggs, sperm, or human
embryos that are then passed down to succeeding generations
known as germline gene editing. Research that attempts to alter
the human germline raises important issues in so many different
ways about safety, risk, social, economic, ethical, and
regulatory considerations. So although more remains to be done
before these technologies can be deployed safely, their
availability certainly intensifies this debate among scientists
and physicians about such research.
Here in the United States there are legislative
prohibitions on the use of federal funds for research of human
embryos and there exist constraints on such research when
subject to oversight by the U.S. Food and Drug Administration
or other government agencies. These constraints, however, do
not apply to work done internationally without federal funds
and without the intent to seek federal approval of any product
of that research. So clearly, we have reached a critical
juncture in genetic editing research and guidance is needed.
The National Academies of Sciences, Engineering, and
Medicine are prepared to provide that guidance based on an in-
depth review of science underlying gene editing, the potential
benefits, and the valid concerns raised by this research.
Toward that end, our initiative on human gene editing research
is already underway. Just last week, we held the first meeting
of a multidisciplinary advisory group that will help us steer
our initiative and ensure the Academies' efforts are
comprehensive, inclusive, and transparent.
Since much of this research is done internationally, the
Academies will convene a global summit to obtain multinational
perspectives on recent scientific development in human gene
editing and the associated ethical and governance issues.
Concurrently, we'll appoint an expert committee to conduct a
comprehensive study of the scientific underpinning and
clinical, ethical, legal, and social implications of human gene
editing. We hope that we will come up with recommendations
which can inform the Nation for decisions in this area.
All of us--scientists, physicians, policymakers, and
public--want to do everything possible to ensure the scientific
and medical breakthroughs benefit all of mankind and do no
harm. The Academies are certainly ready to help.
I would be very happy to answer any questions the
Subcommittee may have. Thank you.
[The prepared statement of Dr. Dzau follows:]
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Chairwoman Comstock. And Dr. Doudna.
TESTIMONY OF DR. JENNIFER DOUDNA,
PROFESSOR OF BIOCHEMISTRY AND MOLECULAR BIOLOGY,
UNIVERSITY OF CALIFORNIA, BERKELEY
Dr. Doudna. Good afternoon, Chairwoman Comstock and the
rest of the Members of the Committee. It's a great pleasure for
me to be here and have the opportunity to talk with you about
science that I've been involved with from its origin and
involved in leading the discussion of where it's going.
I wanted to start by saying that this is research that
originated as a basic science project funded in part by the
National Science Foundation. We did not aim to develop a genome
editing technology but in the course of the experiments that we
were doing, it became clear that what started as a study of a
bacterial immune system, the way bacteria fight the flu, could
actually be reengineered and re-harnessed really as a
technology for changing sequences in the genomes of cells and
whole organisms.
I wanted to tell you a little bit more about the science
behind this to explain a little bit about how it works and why
it's revolutionary. So I think what really makes this distinct
from other ways of manipulating DNA and cells is that it's a
very simple system. It relies I would really make the analogy
to software that you use for your computer. Here we have a
protein called Cas9 that can be easily reprogrammed by using a
short piece of nucleic acid called RNA that enables this
protein to be directed to essentially any DNA sequence in a
genome of an organism. And because genome sequencing has become
very prevalent and is becoming less and less expensive, we have
an exciting convergence of technologies that give us
information about the entire genome in a cell or an organism
and now a tool that allows scientists to change that sequence
in a very precise fashion so we can do things, as was mentioned
in the opening statements, like correct mutations that would
otherwise lead to genetic disease.
So this is, I think, a very exciting moment in biology.
It's opened up a lot of opportunities for research, for
clinical applications in the future, but it also raises various
questions about the way that this technology should be employed
going forward, and in particular in our discussion today the
question of whether and when this technology should be employed
to change the sequence in the human germline in eggs or sperm
or embryos that would lead to a genetically modified person
that would be a mutation that could be passed down to their
children.
And I realized fairly early on in our research that this
technology was likely to be applicable in the human germline,
and that led me to initiate a discussion initially with some--a
fairly small group of scientists in California. We met in
January of this year in the Napa Valley to discuss this very
issue and we spent a day. We had--that small meeting included
scientists, clinicians, as well as bioethicists to discuss the
various issues around human germline editing, and that meeting
resulted in a perspective that was published in Science
magazine about two months ago that was referred to in the
opening statements for--that called for a prudent path forward
in any kind of clinical application of germline editing in
humans.
I do want to point out that our perspective favors research
in this area. I think we feel as scientists that it's very
important to have data so that we can make informed decisions
about future potential applications, and I think this is a--I
think many of us appreciate this is a technology that could be
very helpful for people that have inherited genetic disorders.
However, to ensure that any kind of application clinically in
the human germline was safe and really was used in an ethical
fashion, we do need to understand how this technology operates
in those types of cells.
Thank you.
[The prepared statement of Dr. Doudna follows:]
[GRAPHICS NOT AVAILABLE IN TIFF FORMAT]
Chairwoman Comstock. Thank you.
Now, we'll hear from Dr. McNally.
TESTIMONY OF DR. ELIZABETH MCNALLY,
PROFESSOR OF GENETIC MEDICINE,
PROFESSOR IN MEDICINE-CARDIOLOGY AND BIOCHEMISTRY
AND MOLECULAR GENETICS;
DIRECTOR, CENTER FOR GENETIC MEDICINE,
NORTHWESTERN UNIVERSITY
Dr. McNally. Thank you.
On behalf of Northwestern University, I'd like to thank
Chairwoman Comstock and Ranking Member Lipinski for inviting me
here today.
I'm Elizabeth McNally. I'm the Ward Professor of Genetic
Medicine, and I direct the Center for Genetic Medicine at
Northwestern. I'm a cardiologist and I specialize in providing
care for patients and families with inherited forms of heart
disease. Over the last decade, we've seen a dramatic increase
in available genetic testing and we now routinely provide
genetic diagnosis, risk assessment, and importantly, risk
reduction for genetic diseases that affect the heart.
Diseases like cystic fibrosis, Duchenne muscular dystrophy,
sickle cell anemia are those that are caused by mutations in
single genes. The gene editing techniques that we are here
discussing offer the opportunity for permanent lifelong
treatment of those disorders. With advances in DNA sequencing
technology, it is now possible to sequence an individual genome
in a day. For less than the cost of an MRI, a genome can be
analyzed with high accuracy pinpointing single gene mutations.
The Office of Rare Diseases identifies nearly 7,000 rare
diseases and many of these are genetic in origin, often arising
from single mutations. The ORD estimates that nearly 30 million
Americans are affected by rare diseases. More than half of rare
diseases affect children.
Concomitant with advances in genetic diagnoses, there are
parallel leaps in genome editing. CRISPR/Cas9 represents a
significant advance for genome editing. Because of the co-
development of gene editing and stem cell biology, there is
significant potential clinical application. Induced pluripotent
human stem cells can be made from blood, skin, and other mature
human cells. For my field, cardiology, skin cells can actually
form beating heart-like cells in a dish allowing us to discern
how mutations cause disease and letting us test how to correct
these diseases. The human population is not placed at risk by
these experiments in cells and it seems fair to say that the
human population would actually be harmed by not doing these
experiments since the research offers the potent opportunity to
improve human health.
Stem cells of the bone marrow, muscle, skin, and other
organs can be isolated and edited. With these methods, it would
be possible to cure sickle cell anemia or Duchenne muscular
dystrophy. In mice, CRISPR/Cas9 mediated correction of
fertilized eggs corrected the defect for Duchenne muscular
dystrophy. The method, while imperfect, was associated with a
remarkably high correction rate.
Recently, a group of distinguished scientists called for
careful consideration of gene editing in fertilized oocytes
fearing the potential for germline gene editing and ultimately
human eugenics. These discussions were enhanced and prompted by
the recent report which we've heard about from Liang, et al.,
which described the efforts using CRISPR/Cas9 in fertilized
oocytes.
A regulatory framework for gene editing should encompass
several key points. It should permit research to optimize and
improve CRISPR/Cas9 and related technologies. It should permit
in vitro and cell-based gene editing technologies, including
those in embryonic and induced pluripotent stem cells. It
should permit in vitro and cell-based editing with the intent
to reintroduce cells into humans as a therapeutic measure for
somatic cells. And it should permit the generation of gene-
edited animals for the purposes of scientific research. It may
consider limiting or even prohibiting gene editing under the
circumstances where human transmission of gene-edited germ
lines would occur.
But would we ever really consider germline gene editing? So
we should consider the scenario of pre-implantation genetic
diagnosis, otherwise known as PGD. PGD is pursued by families
to avoid transmitting genetic diseases. PGD involves in vitro
fertilization coupled with genetic testing. PGD is not covered
by insurance, and yet for some families, they make this choice.
These may be families who are already struggling with caring
for one disabled child and who cannot care for a second
disabled child.
PGD is a personal option and one that is made solely by
parents and families. In principle, it is possible that the
efficiency of genome editing will improve so that pre-
implantation genetic correction could accompany PGD. With this
process, gene editing to correct and eliminate a genetic
disease could become reality. While the temptation may be to
ban or limit this possibility, we should do so only with
caution. Parents of children with genetic disease express
significant concern, responsibility, and often dismay for
having passed on mutations to their children. A parent's desire
to protect children is undeniable. As a society and as a
nation, we protect children.
It may be tempting and easiest to ban gene editing where
germline transmission could occur, yet the justified use of
this approach is certainly conceivable and may one day be
appropriate.
Thank you.
[The prepared statement of Dr. McNally follows:]
[GRAPHICS NOT AVAILABLE IN TIFF FORMAT]
Chairwoman Comstock. Thank you.
And Dr. Khan.
TESTIMONY OF DR. JEFFREY KAHN,
PROFESSOR OF BIOETHICS AND PUBLIC POLICY;
DEPUTY DIRECTOR FOR POLICY AND ADMINISTRATION,
BERMAN INSTITUTE OF BIOETHICS,
JOHNS HOPKINS UNIVERSITY
Dr. Kahn. Thank you. Chairwoman Comstock, Chairman Smith,
and Ranking Member Lipinski, thank you for the opportunity to
testify today on this timely and vitally important subject.
As you heard in the introductions, I am a Professor of
Bioethics in Public Policy at the Johns Hopkins Berman
Institute of Bioethics in Baltimore.
Also relevant to my comments today, I am also currently
Chair of an Institute of Medicine Consensus Study commissioned
by the FDA on ethical and social policy considerations of novel
techniques for prevention of mitochondrial transmission in
women to their offspring. Given that this study is considering
issues related to the topic of today's hearing and the work of
that committee is ongoing, I will restrict my comments to
general observations and an overview of ethical and policy
landscape related to gene editing.
I'll focus my comments on three main topics: first, policy
history and related areas of science and biomedical research;
second, ethical issues raised by gene editing technologies; and
third, relevant existing ethical frameworks and approaches to
oversight.
The relevant policy history started in 1975, and we heard
some mention of this earlier, with the Asilomar Conference on
recombinant DNA molecules whose summary statement focused on
containment of the risks of creating and working with
genetically modified organisms. And with the admonition to
avoid experiments that ``pose such serious dangers that their
performance should not be undertaken at this time,'' along with
a call for continuing reassessment of issues arising in light
of new knowledge gained with the experience of the then-new
genetic technologies. And we've heard from Dr. Dzau that the
National Academies are effectively taking on the same role 40
years later.
These voluntary suggestions that came from the Asilomar
summary gave way to more robust oversight as the use of genetic
technologies became more refined and with the initial attempts
to treat disease in humans. It should be noted that that's 40
years ago, and in the current environment, it would be very
difficult for voluntary statements from a collection of even
esteemed U.S. scientists to prevent research from going forward
internationally, as we've seen already with the publication of
the Chinese laboratory experiment.
The ethical issues posed by gene editing and related
technologies for modifying human DNA fall into three general
categories of concern: first, the implications of the
modification of germline DNA, and we've heard some about that
already; second, the implications of interfering in processes
that should be off-limits to humans. Sometimes those are sort
of generally termed ``playing God,'' and that's problematic in
some people's minds; and third, the potential for selection or
introduction of traits for other than treatment or avoidance of
disease, such as physical or behavioral traits or even
enhancements.
The focus of much ethical analysis in the application of
manipulation of genetic information in humans has been on
changes that affect the germline, that is changes that are
heritable and therefore able to be passed on to future
generations of individuals. The basis of these concerns relate
to the uncertainty of the effects of genetic notification, the
inability to ``undo'' unintended genetic changes or limit their
effects, and the risks of passing on such unintended changes
and their consequences to future generations. And that would of
course go on forever.
These ethical concerns have been addressed through a range
of approaches in order to limit certain types of research or to
provide prospective oversight prior to particular proposals
being undertaken. We heard from Dr. Dzau that there are
restrictions on federal funding of research that involves human
embryos. Privately funded research is not affected by these
restrictions, though the convention is that research on embryos
should take place no later than 14 days after fertilization,
and that's a limit also accepted by most countries engaged in
research on human embryos. I should also note that there seems
to be growing agreement that research should be restricted to
nonviable human embryos.
There are a number of institution-level oversight
mechanisms that will apply to gene editing. That includes
Institutional Biosafety Committees, which are charged with
overseeing research with recombinant or synthetic nucleic acid
molecules; Institutional Stem Cell Research Oversight
Committees, which are charged with, as their name implies,
research on human embryonic stem cells and related areas of
research. And as the technologies are introduced into human
subjects, Institutional Review Boards will be charged with
overseeing any potential use on humans.
Lastly, there's a role to be played by the scientific
publication community. They have--journal publishers have an
increasingly important role to play in setting and enforcing
standards of behavior within the scientific community since
publication of findings in the peer-reviewed scientific
literature signifies the endorsement of the community of
researchers.
Journals also play an additional critical role with
requirements on the ethics standards being respected,
assurances authors' contributions are duly noted, and that
human subjects are protected. So there's a role to be played on
the part of the journal publication process that will restrict
the potential of any unethical research going forward.
Let me conclude by saying the United States has played a
leadership role in this area in recombinant DNA and has the
opportunity to do so going forward. There will be gaps
identified in the process that the National Academies has set
out on that need to be identified and addressed, and it is an
appropriate time to consider what those ought to be.
Thank you.
[The prepared statement of Dr. Kahn follows:]
[GRAPHICS NOT AVAILABLE IN TIFF FORMAT]
Chairwoman Comstock. I thank the witnesses for their very
interesting testimony.
And now I remind Members that Committee rules limit
questioning for five minutes.
And the Chair--as Chair, I recognize myself for five
minutes.
So I wanted to hear a little bit more, Dr. Doudna, from
what you mentioned where you had initiated the discussion with
the scientists in California and bioethicists and others to
address this. Some of the key--and maybe expand a little bit
more on some of the key issues you found and how we avoid maybe
where China might go and how we do define those boundaries and
kind of what some of the concerns were that were raised. And if
anyone else would like to address that, too, but I thought I'd
start with you and maybe expounding a little bit more on this
group.
Dr. Doudna. Sure, thank you.
I think, you know, what was interesting to me in that
conversation was that it was a wide-ranging discussion that
started with sort of the--maybe the way that we've been
discussing this technology so far here in the Committee and
eventually got to a point where, as somebody around the table
said, you know, there may come a time when we would consider it
unethical not to do editing in the germline for certain kinds
of applications such as some of the things that Dr. McNally
mentioned.
So I think that it's very important to appreciate that, you
know, this is a powerful technology that is--you know, we're
sort of looking at it here from the perspective of safety and
ethical concerns but I think they're also--you know, that can
be turned around. And that was something that came out of our
discussion in California that I found very interesting.
And the other thing that we discussed was the fact that,
you know, this technology, unlike previous technologies for
genome editing, is very simple to employ relatively. I mean
it's something that, you know, people that have expertise in
molecular biology can fairly readily use in their laboratories.
So I think, you know, the reality is that it would be very hard
to really put regulations on this in terms of research
applications.
And I think that means that we just have to be thoughtful
about providing leadership in terms of the--you know, the--as
Dr. Kahn was saying, in terms of the way papers are published
and reviewed among scientists so that, you know, the scientific
community helps to provide the kind of direction and, you know,
vision for the way this should move forward that hopefully will
be respected by many others. But I think the reality is that
it--you know, it is a technology that's just very widely
available now and is being employed worldwide.
Dr. Dzau. I'd like to echo what Dr. Doudna said. I think we
at the Academies feel very privileged to be asked by the
scientists--Ralph Cicerone, the President of National Academy
of Science, myself, got lots of phone calls and emails to say,
you know, the Academy really should take this on because we
have done so in the past, as you heard, during the time of
recombinant DNA, Asilomar conference, the human cloning, and
also the whole issue of stem cell guidelines, as well as
mapping the human genome. So we have to do this.
I think that in the context of what's being discussed, it's
really important that we have people from all different
disciplines, not only scientists but ethicists, legal experts,
medical physicians, and others all engage in this discussion
because at the end of the day what we want to do is to find
what appears to be the consensus of what the right thing to do
is for our country and so we look forward to working on this.
Dr. Kahn. So I would just like to echo what you've heard
from my colleagues on the panel and add a little bit to expand
on what I said about publication. It's difficult for the
scientific community to identify any one thing that it can take
on in an international way, but scientific publication knows no
borders. And there have been calls now for--before publication
of any gene editing research that there be a disclosure of the
ethics review that that research underwent. That did not happen
so far as we know with the Chinese research that was recently
published, and in fact, the reports have been about Science and
Nature rejected that paper when they considered it and at least
in part on ethics grounds. So that would be one way to create
some--a framing of what would be acceptable as determined by
the scientific community itself through the peer review
process.
Chairwoman Comstock. Thank you. And, Dr. McNally, did you
have anything to add? I have a few more seconds before I turn--
--
Dr. McNally. I would also remember that through this
process it's not just the scientists and the physicians and the
regulatory bodies but to also remember the patient advocacy
groups and the patients themselves. They're going to be the
loudest voice in this process and we need to hear what they
have to say.
Chairwoman Comstock. Thank you. I appreciate it.
Now I recognize Mr. Lipinski for five minutes.
Mr. Lipinski. Thank you.
Before I follow up, I just want to make sure we're more
clear on this when we get into the subject.
Dr. Doudna, you and the group that have met, you've called
for a temporary moratorium on the use of the technologies on
human embryos. Is that correct? And what led you to that and
are there particular milestones and discussions of the science
that you're working towards and then see ending the moratorium?
And I want to get the other panelists to comment on that.
Dr. Doudna. So I would say what led us to that initial
meeting in California was the appreciation that this technology
would likely, you know, be functional in the human germline,
and furthermore, that it was possible that people could do this
fairly easily and perhaps working in jurisdictions where there
would not be regulatory oversight of such experiments. And what
was interesting was that at that meeting we actually heard
about the work that was subsequently published for the Chinese
group, so it became apparent that, you know, the subject of
that conversation was very timely.
I think that, you know, going forward we really have to
appreciate the difficulty in putting in place regulations that
will be, you know, followed internationally. On the other hand,
providing oversight and leadership in--by respected scientists
in the United States and with our international partners I
think will be a very important thing to do and that's really
what we wanted to achieve at that meeting was how to proceed
with that sort of approach. And I think now having the National
Academies involved in organizing larger meetings around this
issue is a very desirable outcome.
Mr. Lipinski. Does anyone else want to comment on a
temporary moratorium on human embryos?
Dr. Dzau. So the National Academies' position is that we
need to be thoughtful, comprehensive, scientifically driven,
and independent so we are convening those bodies and obviously
supporting the idea that we should be very cautious. We have
not actually taken the position per se because until our work
is done, you know, we would be looking at what the most
objective way to approach this when our work is done.
So I think some of these meetings are critically important
and important in the sense that we need international
scientists to be involved with this conversation as well. We
have in fact on our advisory board scientists from the Royal
Society in London, scientists from the Chinese Academy of
Science involved with this conversation because it's really
critical to consider all aspects.
As Dr. McNally pointed out, you know, if you're using
certain conditions, I think we have no doubt that this would be
enormously helpful to patients and to mankind. The question is
what are the areas we need to be concerned about?
That being said, I think technology is still early because
even when you look at the Chinese publication, they were
looking at incomplete editing and many other issues that
research has to go forward to understand the safety, the off-
target effects, and the efficacy before human application. So
that's our position.
Mr. Lipinski. Okay. Dr. McNally?
Dr. McNally. I would like to echo what Dr. Dzau just said
which is that I appreciate very much the leadership by Dr.
Doudna and the group of scientists that got together but I
think the IOM convening an international effort to really look
at what the possibilities are I would think it's reasonable to
wait until we learn what that outcome is. It's important to
have a careful and to have an international look at what the
best recommendations really are at this point in time.
Mr. Lipinski. Dr. Khan?
Dr. Kahn. Just very briefly, the kind of work people are
talking about on an international level is really critical in
establishing principles and guidelines for how to move forward.
I think moratoria--blanket moratoria are probably not what we
need but figuring out when we can go forward and how and under
what kind of restrictions. So certainly in vitro only and
probably, you know, for a very long time until it's determined
that the milestones have been met in order to move forward into
humans. So that's the good work that entities like the
Academies can engage in and I think critical at the
international level.
Mr. Lipinski. Thank you all very much. It's--yeah, I think
there are very difficult ethical questions we need to deal with
here and I know myself I certainly don't know enough about the
technologies, some of the specifics there, and I think that
makes--certainly makes a difference. And then we do get to a
question that Dr. McNally said there are things that we
certainly want to cure and then the question always is how far
do we take this? But we're certainly not going to solve that
here so thank you very much.
Chairwoman Comstock. Thank you.
Now I recognize Mr. Moolenaar for five minutes.
Mr. Moolenaar. Thank you, Madam Chair.
And thank you for your presentations today and my
compliments to you on the work you're doing. It's very
sophisticated and it seems that it has tremendous potential for
good.
On the area of ethics of this I wanted to just explore a
few different areas. Dr. Khan, I wanted to start with you. When
you're advising on the ethics of a new genetic technology, are
there certain ethical lines that should never be crossed, and
if so, how are those lines drawn?
Dr. Kahn. That's a great question and how much time do we
have I guess is going to be part of my answer. But of course
those of the first kind of questions that we ask.
I will say there has been a long-standing line that has not
been crossed and that is modification of the human germline.
That has held for decades since the beginning of recombinant
DNA technology was available and begun to be implemented.
One thing that none of us have actually talked about is the
recombinant DNA Advisory Committee, which is a committee of the
advisory to the Director of the NIH, which has in its
guidelines a statement that they will not consider any proposed
research that modifies the human germline. So it's effectively
a prohibition from that research going forward. Now, it only
applies to research that is subject to the oversight of that
committee, but that has been a bright line.
The other thing which we sort of skirted around but haven't
maybe set explicitly is that when there's such uncertainty
about the risk and the outcomes, we go slowly. So that's the
kind of a soft answer to your question, a mushy one, but I
think that's an important principle to--just to articulate in a
way that's explicit. When we know it's time to go forward is a
harder question but we always start slowly, especially when
we're talking about potentials for modifying humans.
Mr. Moolenaar. Thank you.
And then, Dr. Doudna, you're one of the new developers of
this new technology, and what was it that first sparked your
concern over the ethics of its use, whether it was in China or
when did you start being concerned about that?
Dr. Doudna. I guess I realized the potential for this
technology to operate in the germline first when scientists
began to do experiments of that nature in animal models of
disease, including mice and rats, and then it really came home
to me in--it was last year--may be almost a year-and-a-half ago
that a group again from China published a paper in which they
had modified the germline of monkeys and made genetically
modified monkeys. And that actual monkey model is used very
commonly for studying human disease and so it seemed very
likely at that point that there was no reason to think the
technology wouldn't also work in the human germline.
So, you know, I think we've seen now in the scientific
community that this technology is very democratic in the sense
that it works across many different types of cells. It doesn't
seem to be limited to a particular system.
Mr. Moolenaar. And what role does--you know, I guess one of
the things that occur to me is the whole area of consent. What
role does that play in this process when someone is giving
consent or not?
Dr. Doudna. Are you directing that question to me?
Mr. Moolenaar. Yeah--actually, all four.
Dr. Doudna. You know, I would--maybe I would defer that to
Dr. McNally.
Dr. McNally. Well, as a member of an IRB for about 15
years, that's actually--you know, right now, consent in a
research study in that case would be the parent; the mother
would be the person providing consent. If a study were to go
forward right now, that's who would be providing consent
because it would be her materials that were being used for that
purpose. So there isn't--from the standpoint of human subjects
strictly talking like Institutional Review Boards, a fertilized
egg is not an individual that provides consent and also even--
you know, as a--if it were a child, a parent provides consent
for that if that answers your question.
Mr. Moolenaar. Yeah. Thank you.
Dr. Kahn. So it's--I would sort of ask consent from whom
and for what? So you've heard a version of the answer to that
question. If we're talking about the donor of the materials
that would be researched upon, that's one set of questions. If
we're talking about modifying an embryo that might one day be
implanted into a woman's body and developed into a child where
we have a very difficult conceptual problem. How do we think
about consent on behalf of somebody who's not yet been born?
And so those are the really interesting ethical questions that
we will need to confront. We're certainly nowhere near thinking
about doing that kind of application, but those are the kinds
of questions that need to be identified, articulated, and
addressed in efforts that are like the ones the Academies are
taking on.
Mr. Moolenaar. I would agree with that. Thank you.
Chairwoman Comstock. Thank you.
And now I recognize Mr. Tonko for five minutes.
Mr. Tonko. Thank you, Madam Chair.
This hearing shines a light on a difficult but indeed
important issue and I appreciate my colleagues' focus on the
ethical and legal issues surrounding this new technology.
I'm also assured to see that experts in the medical and
scientific community are coming together to debate this issue
and to discuss potential policy implications. However, as we
explore the boundaries of what science is capable of and what
is ethical and what should be legal, we should also take a
moment to appreciate just how remarkable these advances are. We
recognize that these new gene editing technologies, including
CRISPR, are the outgrowth of decades of fundamental research
supported by federal agencies, including the National Science
Foundation.
So to Dr. Doudna and Dr. McNally, could you please speak to
the importance of federal investments in fundamental research,
especially the need to support research that may not have any
known commercial application at the time?
Dr. McNally. Again, how much time do we have?
Mr. Tonko. Well, the Reader's Digest version.
Dr. McNally. I think everybody sitting here at this table
can say it cannot be overstated how important the federal
investment is for research. There are many people who would
love to see a lot of research funded in the private sector but
there are certain aspects of particularly fundamental research
that will never be covered in the private sector. Sequencing
the genome is a great example of that.
And we can't move forward without that federal investment
and I think all of us here would say, you know, it's been
fairly tough times in the last few years with what's happened
with budgets and what's happened with research and watching the
effect that that has had on the scientific community here in
the United States where we have actually seen the size and
shape of the scientific community shrink in the last few years,
especially when we look across the world and we see it growing
elsewhere. So, yes, federally funded research is absolutely
essential for these types of basic observations.
Dr. Doudna. Right, so I echo everything that my colleague
Dr. McNally just stated and I want to also add that, you know,
there's a tremendous opportunity for the United States to
invest in basic science. I mean I think traditionally our
country is been a leader in science partly because we have
invested in science that was, you know, curiosity-driven
research. It was not necessarily targeted on curing certain
diseases, and I think that we've seen again and again,
especially I would say with regard to technologies, they tend
to come from unexpected types of projects such as the CRISPR
system is a great example of that but there are many others.
And I think also it's important to appreciate that
commercially, you know, these things then have big implications
in terms of companies being able to take over and, you know,
develop technologies that are discovered in academic
laboratories but then apply them in all sorts of different
ways.
Mr. Tonko. Dr. Dzau, I think you wanted to respond to that,
too?
Dr. Dzau. Well, I totally agree with my colleagues and
they're particularly emphasizing support for basic research
because if you think about this technology, it was done on
bacteria, and without thinking of application human and look
where it is today. And we can count so many important
breakthroughs that come this way. So the ability to support
fundamental basic research is critically important.
Also, I think along the issues about saving human lives,
creating jobs, is our global competitiveness situation, we are
truly concerned that we don't continue this level of investment
that the United States becomes less competitive than many other
countries which are investing heavily into basic and
translational research.
Mr. Tonko. Thank you.
Dr. McNally, in your testimony you mentioned how these
technologies may be able to be used in somatic or mature cells
to treat and potentially cure diseases such as sickle cell
anemia and muscular dystrophy. Can you please elaborate on this
possibility and what is that range of therapies and cures that
we might only imagine?
Dr. McNally. I think it's widely anticipated that sickle
cell will be one of the first things that's cured by this where
you could take a cell out because it's a bone marrow cell. You
could correct it with CRISPR/Cas and return that person's bone
marrow cells so it's not a transplant situation; you're
returning their own cells to them. And that's ongoing right now
and I anticipate that we will see that.
For my field I work in muscle diseases. Duchenne muscular
dystrophy is a very challenging, challenging area and right now
we're looking at technologies where we're taking small
antisense compounds where we would have to treat that
individual for a lifetime every day with those compounds.
Again, if we could get the cells, correct them, and reinsert
them back in, that would be a one-time treatment and a lifetime
treatment for that individual. So I think we're seeing a few
examples where it's definitely heading that direction.
Mr. Tonko. Thank you so much.
Madam Chair, I yield back.
Chairwoman Comstock. Thank you.
I now recognize Mr. Palmer for five minutes.
Mr. Palmer. Thank you, Madam Chair.
Several folks have mentioned the research on stem cell. Dr.
Tim Townes at UAB is a very good friend of mind and doing
world-class research in that area.
I've got just a few questions. Dr. Dzau and Dr. Kahn, the
United States and Europe have often disagreed on regulations
and policies and other areas of biotechnology, for example,
genetically modified organisms. How does that impact
international scientific cooperation? And do you anticipate a
similar challenge in human gene editing?
Dr. Dzau. Well, the intention is that when you get
scientists, regulators, ethicists together from different
countries, I think responsible individuals would begin to talk
about what would be responsible behavior. That I believe is the
starting point. And I do agree with you that we have some
differences in the regulation. But I think overall in the issue
we're talking about today, which is the application in germline
gene editing, I have a sneaking suspicion--although I don't
want to fully predict this until the work is done--there's
great agreement about the concern about creating successive
generations of individuals whose genes have been altered. So I
have a feeling that we actually will get agreement if not
harmonization of many of these thoughts, and certainly it's our
hope that we will reach that in our initiative.
Mr. Palmer. There are current regulations that prohibit
federal funding for human--for research on human embryos and
the FDA requires--must issue an investigational new drug
application before a biological product may be used in humans.
Do you think these kind of safeguards are adequate to prevent
the kind of experiments that we're concerned about?
Dr. Dzau. I'd like Jeff to answer this as well because, as
you heard, he's in the midst of leading one of our initiatives
on mitochondria DNA replacement.
Mr. Palmer. Um-hum.
Dr. Dzau. But I think we very much look into what is the
right regulatory framework particularly for issues like this,
and I would say that, you know--and because he would have an
opinion but my feeling is that this work needs to be done to
get better clarity about when and how we would regulate some of
these areas.
Mr. Palmer. Dr. Kahn?
Dr. Kahn. Thank you. In answer to your question, I think
that the FDA will play a critical role although it will only
play its role towards the end of the story so the very basic
research will be done prior to anybody thinking about an IND
application or introducing it into a therapeutic context. And
so we need to think about the entire translational pipeline as
it were and all of the issues that will arise along the way and
make sure that we have appropriate oversight for each of them.
The FDA is clearly thinking about the issues that you are
and are trying to figure out how their framework ought to
apply.
So first--for first in human applications effectively, and
then once something is licensed, how to control its use and
dispersal. So one of the things that we all worry about is the
so-called off-label use of the new technology. So even though
the FDA may approve it only for a limited purpose, once it's
licensed, it's hard to control. The FDA has some new tools that
may actually make them more feasible to do and I think as we
get closer to the kinds of technology were discussing entering
the therapeutic marketplace that there will be stronger
safeguards in place.
Mr. Palmer. Well, with these safeguards--and staying on
that line of thought--is there any worry that if the United
States doesn't use this research that we could fall behind our
international competition and, you know, could new regulations
of this technology in the United States put our researchers at
a disadvantage or cause them to move their research overseas,
Dr. Kahn?
Dr. Kahn. I'll let Dr. Dzau and others speak to this, too,
but there always is talk about that and of course it became a
bigger issue when the stem cell research--human embryonic stem
cell research field really began to grow. And there are now
international stem cell research societies which try to address
issues that are clearly not governed by borders. And what we
don't want of course is to have people who are doing the best
science in the world think about leaving this country because
it's easier to do elsewhere. So we need appropriate controls
but not those that squelch the science. Finding that sweet spot
of course is the challenge.
Mr. Palmer. One last question and you can follow up on that
as you answer this also, but do you believe that we'll be able
to get China and the United Kingdom and these other nations to
work together to influence change and Europe to adopt similar
standards--similar safeguards?
Dr. Kahn. Maybe Dr. Dzau can speak to that if that's okay.
Dr. Dzau. Well, we're starting with getting the major
science academies involved so we have the National Academy of
Science and Medicine in the United States; we have the Chinese
Academy of Science where you would think that they have
tremendous influence on the way the conduct of science is being
carried out. We have the Royal Society and we intend to include
many international bodies.
So I think the starting point clearly is with the
scientists saying what would be the right thing to do. One can
imagine that we may have to escalate this conversation further
depending on our findings.
I just want to point out the question that you asked, which
is the regulation aspect of this. In fact, you know, we do need
a lot more clarity in this country. We haven't talked about the
use of gene editing in nonhuman cells, plants, insects, and
those changes are--that science is really ongoing. We are
producing possibly new species that would turn around much
faster because of a much shorter cycle time, reproductive time.
So that regulation also has to come in to say what in fact is
considered safe and what's considered as environmentally sound.
And in fact the National Academies is also looking at a study
looking at this issue. And as you know, in this country the
USDA and FDA are involved with animal and plant regulations. So
we're also trying to give the right recommendation to fortify
our regulatory processes.
The final question you asked earlier about what the right
thing to do is I think from our perspective at the National
Academies I think our first issue is human protection and doing
the right thing for society. I understand of course the
potential loss of scientists, et cetera, but I do think that we
have to actually take the high road to say what's right for us
first. And I have a feeling everything else would follow and
fall in the right place.
Mr. Palmer. Thank you.
Thank you, Madam Chair.
Chairwoman Comstock. And I now recognize Mr. Swalwell for
five minutes.
Mr. Swalwell. Thank you, Madam Chair, and thank you to our
panelists.
My first question relates to something that a number of the
Members have brought up, which is it seems that America and our
investments in federally funded research have been in decline,
and as a result, our successes have been in decline and our
ability to attract and recruit and retain some of the best and
brightest scientists may be in decline. So let's just for
argument's sake go back to 1995. I was 14 years old. And the
Human Genome Project was just starting to get off the ground
and many great results came out of that. That was 20 years ago.
Would each witness just say more or less has America and its--
have you seen the investments that we've made as far as
federally funded research, has that made America more or less
exceptional in this field? So just tell me more or less. And
I'll start with Dr. Dzau, just one word.
Dr. Dzau. More.
Dr. Doudna. More.
Dr. McNally. More.
Dr. Kahn. More.
Mr. Swalwell. So I'm confused because each of you has said
that our investments have been on the decline and so you're
telling me that we actually have made more investments since
1995 and you believe we are more exceptional now in these
fields?
Dr. McNally. You picked 1995.
Mr. Swalwell. But comparing----
Dr. McNally. If you said 1995----
Mr. Swalwell. Sure.
Dr. McNally. --to 2005, we would say more. If you would say
2005 to 2015 we would all say less.
Mr. Swalwell. Is that right, less, Dr. Dzau?
Dr. Dzau. [Nonverbal response. Nodded in the affirmative.]
Mr. Swalwell. Dr. Doudna?
Dr. Doudna. [Nonverbal response. Nodded in the
affirmative.]
Mr. Swalwell. Dr. McNally?
Dr. McNally. [Nonverbal response. Nodded in the
affirmative.]
Mr. Swalwell. Dr. Kahn?
Dr. Kahn. [Nonverbal response. Nodded in the affirmative.]
Mr. Swalwell. Okay. So that was my question. You would
agree that we have become less exceptional in the field of
genetic engineering as far as it relates to human DNA since
1995, that we've been on the decline?
Dr. McNally. 2005.
Mr. Swalwell. 2005 is the----
Dr. McNally. Yes.
Mr. Swalwell. --point, Dr. McNally?
Dr. McNally. Yeah.
Mr. Swalwell. So what's exciting about this research and
this field is the potential for us to conquer diseases before
they conquer us. And I look at the example of Huntington's
disease, which affects anywhere from 30,000 to 200,000 people,
and it's a disease that is so cruel it steals your memory and
affects your muscular system.
And I'm just wondering, maybe if Dr. Doudna can tell us and
have others weigh in, what can the United States do
specifically to take leadership in this area if we have the
appropriate funding so that we can conquer these diseases?
Dr. Doudna. So I think I know, what--again sort of maybe
echoing something that I mentioned earlier and that has been
discussed here, I think, you know, the United States has been a
real leader in basic research for a while and all of us are
concerned that we see that edge slipping away over time. And so
I think that, you know, the investment in fundamental research
that will allow scientists to understand, for example, genome
engineering technology like we're discussing today, how does it
operate, how can we deliver it to patients, how do we ensure
that it's operating as we intend and not creating unintended
consequences, that it's safe, that it's effective.
All of those lines of research are going to require, I
would say, a combination of efforts by people like me that do
basic research and people like my colleagues who are medical
doctors and think about clinical issues. We need to be putting
our efforts together and that has to be I think supported by
federal funds.
Mr. Swalwell. And how can we tell the story to the American
people who look to us as a Congress to make the decisions when
it comes to funding with so many competing priorities? How can
we tell them that something--like $1 invested in basic research
where you may not be able to tell us what disease you're going
to be able to cure 10 to 15 years from now but there's still--
the taxpayer is looking to us to, you know, hold accountable
the funding. Like how can we better tell the stories of the
science community about what we could see from this down the
road and how we could truly, you know, attack and cure some of
these diseases? I think that's probably one of the biggest
challenges. And maybe Dr. McNally would want to answer.
Dr. McNally. Yeah, I mean we've seen incredible advances
that have come out of basic research, and I'll talk about my
field, which is cardiology. It was out of basic research of
understanding the LDL receptor that led to statins, the drugs
that probably a lot of people in this room take, and we've seen
a direct translation to a reduction in the rate of heart
attacks. I mean it's a very different world than what it was
when I first heard of my training 20 years ago. We don't see
acute heart attacks like we used to and that came as an outcome
of basic research not that many years ago.
So we can tell the same story for heart disease. We can
tell the same story for many cancers. Cancer and heart disease
are the major things that kill people so we've made huge
headway in that.
Mr. Swalwell. Great, thank you. And, you know, I know every
Member up here has thousands of people in their district who go
to bed on their knees praying that people like you will make
discoveries that will make them or their relatives live
healthier lives. So thank you for what you're doing and
hopefully we can do the right thing here and better fund your
initiatives.
And I yield back.
Chairwoman Comstock. Thank you.
And I now recognize Mr. Westerman for five minutes.
Mr. Westerman. Thank you, Madam Chair, and thank you,
panel, for your invigorating testimony.
Dr. Dzau, what's your anticipated timeline for the
initiative on human gene editing?
Dr. Dzau. We are convening an international summit in the
fall--late fall and that should be a--I think really an
important meeting that will get together international
scientists. As you heard from our previous experience at
Asilomar in the 1970s, you know, one would engage in the
discussions that Dr. Doudna and McNally and Kahn put forth, and
hopefully the findings of that meeting will be published very
shortly after that.
Perhaps equally important is a concurrent deep-dive study
which we're conducting that would involve analysis, research,
the assessment of risk/benefits, as well as a regulatory
framework and ethical issues, and that usually--what we call a
consensus report would take as long as about a year, although
we're hoping that we would try to move it faster for exactly
the reasons that we've been talking about. Such a report with
very specific recommendations which we're willing to put
forward under both public hearing and also closed discussions
will be available to you, to the Nation, and to many others. So
I could say the time frame is late fall to sometime next year
but hopefully as early as we possibly can to put out that
report.
Mr. Westerman. So how great are your concerns that the
initiatives may not be able to keep up with the breakneck speed
of the technology as it moves forward?
Dr. Dzau. This is exactly why we need a summit, a meeting
first, where key scientists--and we're going to engage a large
number--will discuss about what would be considered as good
conduct, good oversight, understanding risk, et cetera, so that
the scientific community which is really driving most of this
research understands those issues and have in general
agreement.
We also believe of course in our study itself that becomes
a definitive document by which you and others can be informed
to say what are the right decisions based on consensus.
Mr. Westerman. So you said the scientific community is
driving the research. As the National Academies' work on the
new initiatives for building the framework, do you believe the
scientific community will embrace and voluntarily follow the
guidelines or will there need to be regulations or laws put in
place?
Dr. Dzau. Well, you know, as you already heard, I think
there are many responsible scientists, particularly the ones
who are leading this field, who feel already that we should,
you know, put a moratorium and not slow it down. So I do
believe that already going into this meeting, although there
may be many different opinions, there's probably general
agreement that we need to slow down this area until we have a
much clearer point of view about where we should be going and
the clarity in terms of regulation.
The problem I'm concerned about is that we rush into this
too fast. We don't really want to and it's such an important
issue. We've got to be very thoughtful. That being said, we
understand the time urgency of the issue--situation.
Mr. Westerman. All right. And the advisory group to the
initiative that was named yesterday, it includes scientists and
researchers from China and the United Kingdom. Do you believe
these participants will help influence Asia and Europe to adopt
similar standards?
Dr. Dzau. We certainly hope so, and in fact I was on the
advisory group. Our intention is that in an international
summit we include a lot more scientists from Asia and every
part of the world, Europe, et cetera, to be part of this
discussion.
You know, it's interesting when we think back on U.S.'s
position. You know, when the Asilomar Conference come about,
the United States was the main show in town about technology,
so among the U.S. scientists, you can imagine there's
agreements, you know, so there's a general way of saying, you
know, what do we do next? Here, we really need to include
international scientists.
Mr. Westerman. So what capacity and infrastructure does the
Chinese Government have in place for regulating human
scientific research?
Dr. Dzau. You know, I'm not that familiar with the
regulation at this point in China. As you heard from my
colleague, Dr. Kahn, there is some speculation over what's
there and what's not there. I think we would hope that that
meeting will bring out with clarity what each country's
position is, what's the regulatory position, what's the
scientific position so that we can all come together and
examine this together.
Mr. Westerman. Thank you, and I believe I'm out of time,
Madam Chair.
Chairwoman Comstock. All right. Thank you.
And I now recognize Mr. Foster.
Mr. Foster. Thank you, Madam Chair.
In addition to the international summit that you're having
this fall it strikes me that a full-blown National Academies
study may have merit to do a deeper dive into this. And so, Dr.
Dzau, would a letter signed by Members of Congress, for
example, help you in recruiting assistance for this sort of
effort?
Dr. Dzau. I think it would be outstanding in fact if we got
a letter from Congress on this. We took this upon ourselves as
a National Academy because that's what we do, and we know it's
the right thing to do. We have the support of scientists and
others to say go forward. But I think it would be tremendously
impactful if Congress would provide us with that kind of
support a mandate to go forward with this.
Mr. Foster. Okay. Just a quick question, today what's the
rough cost and time to get a mouse model with a specific
genetic modification? Does anyone--just roughly within a factor
of two--you know, is it $10,000 or $5,000 or----
Dr. McNally. Yeah. Well, with CRISPR/Cas initiated, yeah,
you'll probably decrease the cost in half and decrease the time
in half. So if it was $25,000, it's probably closer to 10 now,
and if it was a year, it's probably closer to 6 months. That's
counting breeding time.
Mr. Foster. Well, when--so one of the things slowing down
the application of this is a lot of--sort of two classes of
worries about potential dangers. The first is so-called off-
target effects where, in addition to the genetic modification
you want, you get inadvertent modifications to the genome. And
it's my understanding that the technology is evolving rapidly
and that--I was just wondering if you--I'll ask you to go out
on a limb I guess, and Dr. Doudna first, about--you know, if
you just look at the rate of progress on this, what is the
rough timescale where we can expect--where we might expect
you'll be in a position that it could be used, you know,
``safely'' on humans?
Dr. Doudna. Well, I think one has to, you know, sort of
distinguish what types of applications we're talking about. I
think if we're considering application to treat a disease like
sickle cell anemia where the editing could be done on cells
that are taken out of the patient and then validated before
they are reintroduced into the body, I feel that that is likely
to happen, you know, the next year or two honestly. I think it
will be very----
Mr. Foster. Right, so no technological development there?
Dr. Doudna. No, because I think we already have the ability
to, you know, validate the correct sequencing--correct editing
was done by DNA sequencing in that sort of a scenario. I think
if you're talking about an application like, you know, we want
to introduce the tool into a patient's body and where you want
editing to occur in the body, then we're--that's further off.
First of all, we don't have the--very good ways to introduce
this into specific tissue types yet, and also we don't have
good ways to validate that the correct type of editing was done
without off-target effects, as you implied. But I think for any
kinds of applications where we can do the validation outside of
the body, that's going to move forward in the next year or two.
Mr. Foster. Okay. And then if I raise the stakes further to
germline editing, is that something that may just never happen?
It may never be reliable enough? Or is it a reasonable guess
that within the next five years that you'll be able to validate
the germline editing, that it has taken place correctly and
with high enough confidence that--
Dr. Doudna. Well, I'm very interested to hear my
colleagues' answer to that question but I guess my answer would
be that it will depend on the way that research is enabled
around, you know, that sort of application. I think if it's
possible to do experiments in germ cells so that we can
understand how this technology works, operates in those types
of cells, then I think, you know--boy, it's always hard to put
a timeline on things but, you know, certainly within a few
years it'll probably be to the point where one could, you know,
employ it for that sort of application. But I don't know if
you--my colleagues would agree with that or not.
Dr. McNally. I agree. I think that's a reasonable timeline,
five, ten years if you had to guess.
Mr. Foster. Yeah. I'm trying to, you know, get some idea--
--
Dr. McNally. Yeah.
Mr. Foster. --of what the response time from Congress and
our society has to be for that.
There's a second class of potential dangers having to do
with just misunderstandings about what the effects of a
specific genetic change will be on the characteristics of the
adult organism. And, you know, over the spread of, you know,
different things from simple conditions like sickle cell to
complex things like, you know, personality, you know, what is
your guess for the timescale that we're looking at there from
right now to never?
Dr. Doudna. My answer is certainly much longer. I think
we--I think--and that--to me that's not limited by the genome
editing technology as much as it's limited by our knowledge of
the human genome.
Mr. Foster. Okay. Thank you. My timer has gone down. I
yield back.
Mr. Moolenaar. [Presiding] Thank you. I now recognize Dr.
Abraham.
Mr. Abraham. Well, after I read you all's testimony last
night I went on and read each of you all's bios. Your parents
must be very proud.
We all in this room I think understand the potential that
this type of research can lead to not only in the human
endeavors but in plant technology, curing world hunger. So it's
applicable to so many aspects of humanity.
And to--I think it was Dr.--your point, Dr. McNally, that
it probably would be unethical if we have a child with sickle
cell in the ALL and this therapy is available not to offer it.
Dr. Doudna, I salute your intelligence for recognizing it
even though I know you weren't particularly looking for the
CRISPR/Cas9 technology that you recognized it. I compared it
last night--I was reading--to Fleming discovering penicillin.
He had been--I think maybe this CRISPR can save as millions of
lives as penicillin has, so kudos to you guys for what you do.
I guess the question I'm leading up to, the old adage if
you get two doctors in a room, you get three different
opinions, as we know very true. That's certainly on my end of
the stick.
Dr. Doudna, you published I think an article in a science
magazine that you wanted this moratorium and, Dr. Dzau, you've
been pushing for. Are you guys getting some pushback from
members of your community that says, you know, no, we don't
need a moratorium and let this thing go? Let this genie out of
the bottle and don't put it back in?
Dr. Doudna. Well, I can tell you what I'm seeing. I think
that, you know, at around the same time that we published the
perspective in Science magazine a related perspective was
published in Nature magazine from a different group that
actually called for I would say real moratorium even on
research. So that group basically was advocating not proceeding
with any kind of research on human germ cells using genome
editing technology. And I just want to point out that in the
group that I met with in January, we actually discussed that
and felt that actually we--in our opinion research on those
types of cells, appropriately regulated, should be enabled,
just not clinical application.
Mr. Abraham. Dr. Dzau, when--Dr. Kahn, when you had the--I
think it was back in 1975 I was reading last night y'all had a
recombinant DNA moratorium that you tried to put forth
voluntarily. In the international community, was that followed?
Has that been pretty much adhered to throughout the last few
generations?
Dr. Kahn. So a little bit before my time but it's a
landmark in the area of science policy and then it was a
voluntary moratorium instituted by the scientific community.
The truth is we haven't seen anything like that since. It was a
very important undertaking. And I think when the scientific
community got together to talk about the implications of
recombinant DNA technology at that time, they weren't sure
whether the scientific community would follow what the----
Mr. Abraham. Much like now.
Dr. Kahn. Much like now. It's 40 years later and the
scientific community is very different today than it was in
1975.
Mr. Abraham. For sure.
Dr. Kahn. So we were undisputedly the leaders in the world
of that science in 1975. As everybody has said, the technology
now is much more widespread and much easier to implement, as
Dr. Doudna has said, making it much more difficult for any one
community of scientists to actually speak on behalf of the
whole.
Mr. Abraham. Well, we think--we can probably say
realistically that America will lead in the discussion of the
ethical and moral implications of this, but to follow up with
your statement then, as Americans or as the United States----
Dr. Kahn. Um-hum.
Mr. Abraham. --scientific community, if we should see an
element get outside the bounds, can we do anything?
Dr. Kahn. Yeah, it's a great question. And as I said in my
testimony and in my statement that you read and I reiterated
today that the journal publication community has a very
important role to play here. What--your research doesn't really
mean much unless your peers have reviewed it, called it good,
and then it gets published in a credible place. So that's a
really important barrier. That doesn't mean people won't try to
do things that aren't ethical and then try to get them
published, but it's a--has a sort of strong inoculating feature
I would say.
The other thing that Dr. Doudna pointed out but I'll
reiterate is that there's been a little bit of a disagreement
in the scientific community on the topic of gene editing, about
whether there should be a moratorium only on clinical
application or on something more widespread. And so that's a
healthy debate to have and it's great that we're having it and
it's great that the Academies are bringing it out to the
international level. So that's exactly the discussion we ought
to be having.
One last thing I'll say is that people around the world
want to be part of the scientific community. There's a very
strong incentive for them to behave, right, to follow the
conventions which make them a legitimate member and I think we
shouldn't underestimate the power of that. So, yeah, there
might be fewer restrictions in other parts of the world but
those people want to publish in Science and Nature just like
American scientists do.
Mr. Abraham. Yeah. Thank you.
Mr. Chairman, I'll yield back.
Mr. Moolenaar. Thank you.
I now recognize Mr. Sherman.
Mr. Sherman. Thank you, Mr. Chairman, for holding these
hearings. This has been an area of intense interest on my part
since the year 2000 when I went to the Floor and said that the
most important decision we will make this century is whether
our successor species is carbon-based or silicon-based, whether
the new and intelligent species on this planet is the product
of genetic engineering or the product of computer engineering.
Some of you will remember I served on this Committee in the
107th and 108th Congresses and this was pretty much my main
reason for serving on the Science Committee.
I should bring to the attention of this Subcommittee that
on June 19, 2008--transcript available--the relevant
Subcommittee of Foreign Affairs had a hearing titled ``Genetic
and Other Human Modification Technologies: Sensible
International Regulation or a New Kind of Arms Race?'' And in
fact the analogy to what we're talking about here is the only
other technology that was equally explosive perhaps, and that
is nuclear weapons technology. In 1939 Albert Einstein wrote to
Roosevelt saying what was possible and policymakers had only
six years before that technology literally exploded onto the
scene. Thank God we've got a little bit more time but the
Nonproliferation Treaty took many decades after 1939 or after
1945 and I think could be a good model for what we need here.
Dr. Kahn, it may be too long to list but I don't know
whether America is exactly number one in this technology or
whether Britain or China might be slightly ahead, but we're all
within, I think, a few years, but there are a whole bunch of
other countries either at that level or maybe four or five
years behind. Can you even list the countries that within five
years could be where we are now?
Dr. Kahn. I don't know--
Mr. Sherman. Are we talking a dozen, two dozen?
Dr. Kahn. I'm not sure that it's--that I or anybody could
do that, and in fact, I'm not sure that it even requires
countries. It's individuals who have access to the capacity--
Mr. Sherman. Um-hum.
Dr. Kahn. --which, as Dr. Doudna has said, is actually
fairly democratic I think was the term that she used. So in a
way, you know, it's about where people have the laboratory
capacity and that's almost anywhere in the world.
Mr. Sherman. Well, thank God nuclear weapons take an
industrial scale. And although they reflect only 1945
technology, we've seen in Iran that you have to do something
big, you have to spend billions of dollars, it has to be
visible to the world that you're doing something. You seem to
be saying that what we're concerned about here could be a lot
cheaper and take place in a laboratory basement?
Dr. Kahn. And I'll let my colleagues speak to the concrete
answer to that question but I think exactly that kind of point
is really important for how we think about what appropriate
oversight, regulation, guidelines need to be--
Mr. Sherman. And I want to pick up on Mr. Foster's question
about time frame, but one of the concerns we will have is that
countries will see this as, oh my God, it might be terribly
unethical but it gives us a leg up militarily or economically.
Damn the torpedoes.
Leaving aside engineering intelligence and looking to
things that would--other than that that would affect soldiers,
soldier is a little better if they've got courage, stamina, and
strength. We're already at a point where drugs are going to be
used by various militaries to impart those characteristics to
their soldiers but then we can go further to genetic
engineering. What is the time frame before there's genetic
engineering that would do the simplest of--I don't know which
of those three is easiest--would give a soldier either more
strength or more stamina or, say, more courage, more
willingness to charge out? Is there any way to say that that
soldier is five years from now, fifteen years from now, or are
we in the world of science fiction? Anybody venture a guess?
Dr. McNally. Science fiction.
Mr. Sherman. Okay. Well, we'll be in a position I think
next decade where at least--well, already many militaries are
using drugs on their soldiers and then the next step will be to
use the next element of medical technology, not drugs, but
genetic engineering.
Does anyone have--I mean we're--the first and most ethical
use of this technology is to remedy maladies. The next step
will be to allow parents to have kids that have all the best
characteristics of anyone in their family or in the world. And
then we'll go to giving kids unprecedented capacities, and at
that point we're talking maybe human, maybe trans-human. What--
does anyone here have any view as to how long it will be before
we can affect the intelligence of either people--either adults
or of germ cell--the germ line?
Dr. McNally. I'll dive in.
Mr. Sherman. Dr. McNally is coming close.
Dr. McNally. I'll dive in.
As Dr. Doudna has said, the limitations of engineering
things like intelligence--
Mr. Sherman. Um-hum.
Dr. McNally. --are far more limited by our genetic
observations--
Mr. Sherman. Um-hum.
Dr. McNally. --than they are by our capacity to do genome
engineering. We have actually very large scale genetic projects
ongoing right now, the 1,000 Genomes Project in the next year
or two we'll be looking at a million human sequences and a lot
of information connected to it. And the simple answer is that
traits like intelligence are not single-gene--
Mr. Sherman. Yeah.
Dr. McNally. They're probably not even entirely genetic is
what people are referring to on a regular basis right now.
There's a whole series of articles written about the missing
heritability for many different traits, things that we thought
were genetic when it turns out we look at the genes, they may
not be so genetic or they are a very high complexity.
Mr. Sherman. So the technology--it's interesting because in
nuclear weapons there's two components. One is weaponizing the
highly enriched uranium, which turns out to be the easy part.
It seems the most dangerous. Oh, my God, you're going to turn
it into a nuclear weapon. The real hard part and the decider as
to which countries have nuclear weapons technology is the
ability to enrich uranium.
Mr. Moolenaar. The gentleman's time is--
Mr. Sherman. If I--it seems like what you're describing is
a situation where the roadmap to what genes do--have what
characteristics is the hard part and the part that will
determine and the actual snipping and replacing and editing,
you guys have that down.
I yield back.
Mr. Moolenaar. Thank you.
Ms. Bonamici.
Ms. Bonamici. Thank you very much, Mr. Chairman. And thank
you to the Chairman and Ranking Member for holding this hearing
about this important topic, and I--my absence for most of the
hearing was only because I was in another hearing. It does not
indicate my lack of interest in the subject.
And I'm really glad that we have this, I agree, very
incredibly qualified panel and I especially appreciate the
gender diversity. As someone who works on education issues and
trying to get more women in STEM, thank you for having a
balanced panel.
So I missed--a lot of the questions have already been asked
but there's a couple of things that I wanted to follow up on.
There's been a lot of attention on using gene editing
technologies in human embryos, and of course we--with the press
from what happened in China, that's getting attention. But I
know that a lot of the research is not in human embryos, so
could you discuss how the technologies are being used in
research today in other areas, including in organisms other
than humans? And also can you talk about the potential promise
from sectors other than healthcare, energy, for example?
Dr. Doudna. Okay. Well, I'll--I can take a stab at that. So
you're absolutely right that the technology is being widely
employed in many different kinds of cells and organisms, and
I'll just give you a couple of examples. I think that in plant
biology this is going to be, you know, equally impactful as the
kind of thing that--kind of applications that we're talking
about here in human health in terms of enabling very, you know,
widespread introduction of genes into plants that could be
beneficial especially for dealing with climate change and other
kinds of environmental impacts in plants. And I'm just--I'm not
a plant biologist but I'm saying this based on conversations
I've had with people that are already doing those kinds of
experiments and are extremely excited about the way that that
research has been enabled.
And then you mentioned biofuels and I think that's very
interesting because I'm aware of several groups that are
actually using this kind of genome engineering for what we call
systems biology, basically being able to make large-scale
changes in the genomes of organisms that will be useful for
producing various kinds of chemicals, including, you know,
biofuels and other very important materials that can be
difficult to obtain in other ways.
Ms. Bonamici. Terrific. And I know Dr. Dzau wants to----
Dr. Dzau. This in fact is a very important area. Today
we're talking about human genome editing but I'm glad you
raised the question about the usage in other living organisms.
Mr. Sherman asked about, you know, what will be the misuse, if
you will, but we do have to think about, you know, the use in
plants, insects, et cetera, you know, what happens if there's
misuse and what would happen to the environmental impact and
who actually gets to decide who's going to do what? And there
are more commercial sources I believe--opportunity for
commercialization in changing coffee beans or whatever that you
can imagine.
So this is an area that in fact--called gene drive that,
again, National Academies are looking very carefully at this
and how to regulate this. So I do think this is to me a very
important area even though our focus is on human gene editing.
Ms. Bonamici. Terrific. And I'm going to slightly change
the topic.
Dr. Doudna--did I say your name properly?
Dr. Doudna. Yes.
Ms. Bonamici. I know you cofounded several startup
companies and we've had conversations in this Committee before
about the challenges in trying to launch companies but also
transferring academic research into the marketplace. So can you
chat a little bit about that and what the challenges have been
and what the Federal Government can do to help with
transferring academic research into the marketplace?
Dr. Doudna. Yeah, this is a very important area and I'm a
real newbie to it. This is actually the first time that
research in my lab has led to something that, you know, had
clear commercial applications. So I can tell you my experience,
you know, being involved in starting companies and raising
money for companies. We've had different experiences I would
say. I've been involved in three different startups around this
technology so far. And I've had a lot of help with one of them
in particular through a--what would I call it? I guess it's a
biomedical research initiative in the Bay area that was
actually funded in part by the State of California. And what
that does is to give people like me who know nothing about, you
know, starting a business some training. We got access to some
legal advice early on. We--I think this Institute paid for the
incorporation of the company initially and then gave us some
support in terms of writing for federal funding for the
company.
I think this kind of support is really important. And as I
talk to my colleagues around the country who are trying to do
similar things, commercializing work coming out of their
academic labs, I hear over and over how all of us who are in
the academic world could really benefit from that kind of level
of support. I'm not sure if it's something that happens at the
federal level or if it's better done lower down, hard to say.
Ms. Bonamici. Thank you so much.
And my time is expired. I yield back, Mr. Chairman. Thank
you.
Mr. Moolenaar. Thank you.
And now I want to recognize Mr. Palmer.
Mr. Palmer. A couple of quick questions. Most of this
discussion I think has been about government research. You're
talking about convening an international summit. I just want to
make sure that when we're talking about implementing safeguards
that this includes the private sector, that they're not running
out there as mavericks. Is that correct?
Dr. Dzau. Certainly our intention, if you look carefully at
the way we put our advisory committee together, we have people
who have great industry experience on it and our intention is
to include industry and, you know, people in the commercial
sector to be in this discussion.
Mr. Palmer. Thank you. I yield the balance of my time, Mr.
Chairman.
Mr. Moolenaar. Thank you.
I now recognize Mr. Foster.
Mr. Foster. Thank you.
It's my understanding that very often there's a computing
bottleneck in our ability to analyze genomes. And I guess, Dr.
McNally, can you tell the Committee about some of the work
you've done at Argonne----
Dr. McNally. Yeah.
Mr. Foster. --which is a facility shared by the Ranking
Member and myself.
Dr. McNally. Yeah, so right now it's--since more than a
year-and-a-half, it's been very possible to sequence a human
genome with the consumable cost being about $1,000, which is an
amazingly low price for a single genome. That doesn't include
the cost of analysis, and so the real rate-limiting step right
now is the time it takes to analyze genomes.
So what we've done is we've actually, working together with
Argonne National Labs, the University of Chicago, and now
Northwestern, we've actually taken a Cray XE6 supercomputer
that's at Argonne and outfitted it with all the computing code
that's available through the Broad Institute so that we can
now, for example, analyze 250 genomes in a weekend if they give
us the whole machine to work. So that dramatically accelerates
our ability to screen through three billion bases of an
individual genome and score it's four million differences that
exist in each one of those genomes, the vast majority of which
are rare and private.
Mr. Foster. And--well, thank you. That's very interesting.
I guess another application of federal investments that are
having an unintended benefit.
I guess for Dr. Kahn, has anyone ever taken the bull by the
horns and actually attempted to draft legislation or
international treaties, you know, at regulating human genetic
engineering or other genetic engineering in the environment?
Dr. Kahn. That's a good question. I don't know that there
have been legislation or, you know, bills proposed and I don't
know about international treaties. There certainly have been
efforts to craft guidelines but they're nonbinding by entities
like the World Health Organization or the World Medical
Association, which has crafted actually fairly well-known
guidelines on human subjects research which is called
Declaration of Helsinki, which tends to be followed but in a
voluntary way and then built into regulation at the national
level. But I don't think that there has been any successful
international regulation.
Mr. Foster. All right, or even proposed--just--you know,
lists enumeration of all of the issues that you have to resolve
when you write rules.
Dr. Kahn. Yeah, I'm not aware, although not a historian of
science. That's a really interesting question that I--maybe
I'll do some looking and see if I can get back to you.
Mr. Foster. I would appreciate that.
Dr. Kahn. Sure.
Mr. Foster. And do you understand right now if you're on a
hospital ship in international waters, who's the regulator?
Dr. Kahn. That's the right kind of question to be asking.
And this sort of issue came up when there was a supposed
cloning of a human being. You may remember back in--when that--
whenever that was, the late '90s, early 2000s--
Mr. Foster. All the----
Dr. Kahn. Yeah, which turned out to be a hoax. But one of
the claims was it was being done in international waters and
out of the reach of any of the national regulations or
governance structure, which, you know, in a way was a helpful
aha moment, right? You need to think about what to do when all
you need is a well-fitted ship that has the laboratory on board
and you're outside of the--any restrictions that an
international treaty or national government might employ.
Mr. Foster. Okay. And I guess one last question. The issue
of gene drives has entered the news and interestingly is with
the potential to sort of take over the genome of an entire
species in the wild in the course of, you know, a few dozens of
generations. And so this obviously has huge environmental
effects and has to be internationally regulated presumably
because of, you know, insects don't normally, you know, obey
national borders.
And so I was just wondering if that is an area where, for
example, this Committee might interestingly have a separate
branch of investigation that all of the applications of this
technology to plants and animals in the wild and in the
laboratory?
Yes, Dr. Dzau.
Dr. Dzau. Mr. Foster, as I mentioned, I think the National
Academies is undertaking such a study. We'd be happy to send
you all the materials, and in fact, as we look at what we are
potentially covering and not covering, we can have a
conversation about what else should be done.
Mr. Foster. Okay. And so the charge is complete for the
study or is it----
Dr. Dzau. Yes.
Mr. Foster. --ongoing? All right. I'd appreciate that.
Thank you.
I yield back.
Mr. Moolenaar. Thank you.
And I'd like to thank our witnesses for the testimony
today, outstanding, and all the Members for the questions. The
record will remain open for two weeks for additional comments
and written questions from Members. The witnesses are excused
and this hearing is adjourned.
[Whereupon, at 3:56 p.m., the Subcommittee was adjourned.]
Appendix I
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Answers to Post-Hearing Questions
Answers to Post-Hearing Questions
Responses by Dr. Elizabeth McNally
[GRAPHIC NOT AVAILABLE IN TIFF FORMAT]
Appendix II
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Additional Material for the Record
Statement submitted by full Committee Ranking Member
Eddie Bernice Johnson
Thank you, Madam Chairwoman for holding this hearing, and I
want to join you in welcoming our distinguished panel of
witnesses.
This afternoon we are talking about new gene editing
technologies that have promising applications in fields ranging
from medicine to energy to agriculture. The Chinese research
paper that prompted this hearing highlights the need to have a
serious examination of the science, safety, and ethics of gene
editing technologies.
I want to thank the Chairwoman and Ranking Member for
putting together this hearing with an impressive panel of
expert witnesses. Additionally, I want to acknowledge Dr.
Foster, whom I understand was instrumental in advocating for
this hearing.
The technologies we are discussing today can alter DNA--the
blueprint of life. There are significant safety, efficacy, and
ethical issues concerning these technologies. What are the
ethical uses of these technologies? Is it ethical to use them
if they could cure a disease? What if they just treated a
disease?
Any applications that would alter germline cells, where
changes are passed down through generations, have additional
ethical issues. For example, is it ethical for the current
generation to consent to changes for a future one?
Although today we are discussing human applications, we
should not forget that these same technologies also have great
potential for use in energy and agriculture. Gene editing could
be used to create biofuels and new crops. Responsible
applications of these technologies could lead to significant
economic growth if the U.S. takes the lead in research and
transferring that research to the private sector.
I look forward to hearing from the witnesses about the
state of the gene editing science and potential applications.
Additionally, the U.S. needs to take a leadership role in
addressing relevant ethical issues so I am glad that the panel
includes a bioethicist to help us better understand what is
involved.
Finally, I look forward to hearing about the National
Academies' plans to address these and other important questions
surrounding this emerging research area.
Thank you and I yield the balance of my time.
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