[Congressional Record Volume 153, Number 186 (Thursday, December 6, 2007)]
[Senate]
[Pages S14821-S14824]
From the Congressional Record Online through the Government Publishing Office [www.gpo.gov]




                           STEM CELL RESEARCH

  Mr. BROWNBACK. Mr. President, I rise to discuss a recent enormous 
scientific breakthrough on a topic that has engaged this body for much 
of the past 8 years. I think this is a day that many of us--I think 
perhaps all of us--have hoped would take place. I ask unanimous consent 
to include in the Record at the end of my remarks an article that broke 
lose right around Thanksgiving.
  The PRESIDING OFFICER. Without objection, it is so ordered.
  (See exhibit 1.)
  Mr. BROWNBACK. Mr. President, this article is by Dr. James Thomson, 
University of Wisconsin. Some may recognize that name. His name has 
been used on this floor many times during the past 8 years on the issue 
of embryonic stem cell research. He is the man who discovered human 
embryonic stem cells about 10 years ago and described them as being 
what is called pluripotent, which means that an embryonic stem cell 
could form any other type of cell tissue in the body, whether it is for 
the eye, brain, bone, or skin. Any type of cell tissue could regenerate 
on a fast basis, and it was thought that these sorts of pluripotent 
embryonic stem cells were going to solve a number of our human health 
problems. Many of my colleagues on both sides of the aisle embraced the 
news and said this is a fabulous thing and we are going to be able to 
now cure a number of people from diseases who have had great problems 
and difficulties, and we want cures for them.
  There was an ethical glitch with it in that it took the destruction 
of a human embryo to get these human embryonic stem cells, and therein 
ensued a fight that engaged the country and engaged the world about the 
tension between cures and an ethical recognition of human life and the 
sacredness of human life. It has been a long debate. I am hopeful that 
the article I submitted into the Record is the bookend on the other end 
of this debate that was started by Professor Thomson and that, in many 
respects, I hope is ended by Professor Thompson and his colleagues.
  In this article they describe a new type of pluripotent stem cell 
that is manipulated by man. They call it an induced pluripotent stem 
cell. This is an elegant and simple process where they take a skin cell 
from an individual and they reprogram it to be able to act like an 
embryonic stem cell, or what they call an induced pluripotent stem 
cell. They then are able to get it to generate more embryonic-like stem 
cells that are pluripotent and which then can be used to treat diseases 
or to study diseases, thus removing the need to develop and have a 
human embryo destroyed, or the origination of the embryonic stem cells, 
thus removing the problem of not being able to get a genetic match so 
that we have to go to a cloned embryonic stem cell, or a cloned human 
to create an embryonic stem cell that matches genetically. You don't 
have to do that. Get a person's skin cells, reprogram them, back in, 
pluripotent, to form any type of cell--elegant, simple.
  There are still many barriers to go on embryonic-like stem cells 
anyway because they have had a problem with tumor formation. But on the 
ethical issue, I am hopeful we are on the other bookend, and it is now 
over; that we don't need to destroy young human life for cures; that we 
don't need to destroy them for pluripotent cells; that we can do it 
much simpler and ethically and that good ethics is good science.
  I put a description up here of what Dr. Thomson said on this subject. 
There was a University of Tokyo professor who came out with an article 
the same day, using a slightly different or modified technique, to be 
able to do this in humans. The University of Tokyo professor had done 
this earlier in mice and now has perfected it in human cells. He came 
out saying the same thing:

       These induced pluripotent cells described here meet the 
     defining criteria we originally proposed for human ES cells, 
     with the significant exception that the induced pluripotent 
     cells are not derived from embryos.

  That was Dr. James Thomson.
  I want to speak about this to my colleagues because we have had so 
many debates on the Senate floor about this topic. I hope my colleagues 
will research this. A number of people in the scientific field are 
saying: Great, but let's not stop embryonic stem cell work and 
destroying embryos for research purposes. Or let's not stop human 
cloning because it appears now that the only reason to clone a human 
would be to bring a human to live birth at this point in time, which 
still has everybody in this body opposed to that type of human cloning.
  It is noteworthy that the ``father'' of Dolly the sheep has said he 
has given up on human cloning to go to this type of technique rather 
than human cloning to provide these sorts of cures and research.
  Mr. President, I also ask unanimous consent to be printed in the 
Record at the end of my comments a Telegraph article from the United 
Kingdom in which Ian Wilmut announced he is shunning human cloning.
  The PRESIDING OFFICER. Without objection, it is so ordered.
  (See exhibit 2.)
  Mr. BROWNBACK. Mr. President, it is my hope that we can move together 
in finding cures and developing research that cures humans that is 
ethical and sound and doesn't destroy young human life.
  We have been able to do quite a bit of this already. We recently 
found there was scientific work done by a Northwestern University 
professor in developing cures and treatments for type I diabetes using 
stem cells. Again, this is adult stem cells, which is ethical and 
moral, no problem with it. The only problem I found with it is that the 
Northwestern professor was having to do this in Brazil rather than in 
the United States to get support and funding. He is saying this:

       Though too early to call it a cure, the procedure has 
     enabled the young people, who have type I diabetes, to live 
     insulin-free so

[[Page S14822]]

     far, some as long as 3 years. The treatment involves stem 
     cell transplants from the patient's own blood.

  For parents who are dealing with juvenile diabetes and those 
difficulties, this is fabulous news in humans. We need more of it, and 
we need it to take place in the United States and not Brazil. Nothing 
against Brazil. I am glad for it to take place there, but I want it 
here for our children. We now have--as I have said previously on the 
floor--73 different human applications for adult stem cells. We have 
not been able to come up with any in the embryonic field yet. I think a 
bigger number--and we will verify this for my colleagues, as it is not 
verified yet--is somewhere north of 400,000 people who are now being 
treated with adult or cord blood stem cells in the United States and 
different places around the world, the majority being U.S. citizens. Of 
course, we don't have any in the embryonic field because it continues 
to struggle with tumor formation as an issue. These are wonderful 
numbers of treatments that we are getting in different human maladies 
and, hopefully, we can verify that number of 400,000 people being 
treated with stem cells, getting heart tissue and spinal cord tissue to 
regenerate, and Parkinson's treatment is coming forward. This is a 
beautiful set of treatments--all ethical.
  I want to look at the budgetary numbers briefly to remind my 
colleagues where we have invested taxpayer funding in this field. It is 
my hope that as we look at the numbers--we have an ethical issue on 
human embryonic stem cell research, and I believe we have crossed over 
the line. I hope we can continue to look at our funding issues, where 
we are putting a lot of money, and have put a lot of money, into 
embryonic stem cell research. We are looking at $140 million in fiscal 
year 2006 and over half a billion since 2002 in embryonic stem cell 
research of both human and nonhuman types. We have not cured a single 
patient yet with that money.
  May I submit to my colleagues that with over half a billion dollars, 
we could be treating and developing these cures in the United States 
and not in Brazil.
  In trying to set aside all of the sharp edges that have now been 
associated with this debate, and focusing just on patients and treating 
people, I hope we will say we are all in this for cures, for treating 
people. So if I could take portions of these funds and put it into 
treating people and getting more people treated for Parkinson's, 
congestive heart failure, or diabetes--all the things that we are 
actually doing in humans today but that need more research in funding--
that we would say: OK, you are right. We don't have to go the embryonic 
stem cell route now. Let's go to where people are getting treated and 
treat people.
  This is about curing people. That is what we have debated and talked 
about for some period of time, curing people. We have one that is 
working and one that doesn't. Yet we have invested pretty heavily in 
this.
  I ask my colleagues if there is some way that we could put the swords 
down and talk about this rationally, stop the fighting and say how do 
we treat people. I believe that is our objective.
  With that, I thank my colleagues for their indulgence in this debate. 
It will continue to come up. The next issue will be human animal 
crosses. I advise my colleagues on this, you will see people pushing to 
cross genetic materials from animals into humans. They are going to say 
it is going to cure a lot of people. I think it is an enormous ethical 
boundary that we should not cross at this point in time, with our 
understanding of life and what it is to be human. I hope before we go 
that route, we will all get together and say we are going to pause for 
a while on this one. This is too big for all of us, and we want to 
think about this for a while--left, right, middle. We have a ways to go 
to get some cures. We are getting them. We don't need to cross over to 
that. We can think about that.
  I yield the floor.

                               Exhibit 1


  Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells

       Somatic cell nuclear transfer allows trans-acting factors 
     present in the mammalian oocyte to reprogram somatic cell 
     nuclei to an undifferentiated state. Here we show that four 
     factors (OCT4, SOX2, NANOG, and LIN28) are sufficient to 
     reprogram human somatic cells to pluripotent stem cells that 
     exhibit the essential characteristics of embryonic stem 
     cells. These human induced pluripotent stem cells have normal 
     karyotypes, express telomerase activity, express cell surface 
     markers and genes that characterize human ES cells, and 
     maintain the developmental potential to differentiate into 
     advanced derivatives of all three primary germ layers. Such 
     human induced pluripotent cell lines should be useful in the 
     production of new disease models and in drug development as 
     well as application in transplantation medicine once 
     technical limitations (for example, mutation through viral 
     integration) are eliminated.
       Mammalian embryogenesis elaborates distinct developmental 
     stages in a strict temporal order. Nonetheless, because 
     development is dictated by epigenetic rather than genetic 
     events, differentiation is, in principle, reversible. The 
     cloning of Dolly demonstrated that nuclei from mammalian 
     differentiated cells can be reprogrammed to an 
     undifferentiated state by trans-acting factors present in the 
     oocyte (1), and this discovery led to a search for factors 
     that could mediate similar reprogramming without somatic cell 
     nuclear transfer. Recently. four transcription factors (Oct4, 
     Sox2, c-myc, and Klf4) were shown to be sufficient to 
     reprogram mouse fibroblasts to undifferentiated, pluripotent 
     stem cells (termed induced pluripotent stem (iPS) cells) (2-
     5). Reprogramming human cells by defined factors would allow 
     the generation of patient-specific pluripotent cell lines 
     without somatic cell nuclear transfer, but the observation 
     that the expression of c-Myc causes death and differentiation 
     of human ES cells suggests that combinations of factors 
     lacking this gene are required to reprogram human cells (6). 
     Here we demonstrate that OCT4, S0X2, NANOG, and LIN28 are 
     sufficient to reprogram human somatic cells.
       Human ES cells can reprogram myeloid precursors through 
     cell fusion (7). To identify candidate reprogramming factors, 
     we compiled a list of genes with enriched expression in human 
     ES cells relative to myeloid precursors, and prioritized the 
     list based on known involvement in the establishment or 
     maintenance of pluripotency (table S1). We then cloned these 
     genes into a lentiviral vector (fig. S1) to screen for 
     combinations of genes that could reprogram the differentiated 
     derivatives of an OCT4 knock-in human ES cell line generated 
     through homologous recombination (8). In this cell line, the 
     expression of neomycin phosphotransferase, which make cells 
     resistant to geneticin, is driven by an endogenous OCT4 
     promoter, a gene that is highly expressed in pluripotent 
     cells but not in differentiated cells. Thus reprogramming 
     events reactivating the OCT4 promoter can be recovered by 
     geneticin selection. The first combination of 14 genes we 
     selected (table S2) directed reprogramming of adherent cells 
     derived from human ES cell-derived CD45+ hematopoietic cells 
     (7, 9), to geneticin-resistant (OCT4 positive) colonies with 
     an ES cell-morphology (fig. S2A) (10). These geneticin-
     resistant colonies expressed typical human ES cell-specific 
     cell surface markers (fig. S2B) and formed teratomas when 
     injected into immunocompromised SCID-beige mice (fig. S2C).
       By testing subsets of the 14 initial genes. we identified a 
     core set of 4 genes, OCT4, SOX2, NANOG, and LIN28, that were 
     capable of reprogramming human ES cell-derived somatic cells 
     with a mesenchymal phenotype (Fig. 1A and fig. S3). Removal 
     of either OCT4 or SOX2 from the reprogramming mixture 
     eliminated the appearance of geneticin resistant (OCT4 
     positive) reprogrammed mesenchymal clones (Fig. 1A). NANOG 
     showed a beneficial effect in clone recovery from human ES 
     cell-derived mesenchymal cells but was not required for the 
     initial appearance of such clones (Fig. 1A). These results 
     are consistent with cell fusion-mediated reprogramming 
     experiments, where overexpression of Nanog in mouse ES 
     cells resulted in over a 200-fold increase in 
     reprogramming efficiency (11). The expression of NANOG 
     also improves the cloning efficiency of human ES cells 
     (12). and thus could increase the survival rate of early 
     reprogrammed cells. LIN28 had a consistent but more modest 
     effect on reprogrammed mesenchymal cell clone recovery 
     (Fig. 1A).
       We next tested whether OCT4, SOX2, NANOG, and LIN28 are 
     sufficient to reprogram primary, genetically unmodified, 
     diploid human fibroblasts. We initially chose IMR90 fetal 
     fibroblasts because these diploid human cells are being 
     extensively characterized by the ENCODE Consortium (13), are 
     readily available through the American Type Culture 
     Collection (ATCC, Catalog No. CCL-186) and have published DNA 
     fingerprints that allow confirmation of the origin of 
     reprogrammed clones. IMR90 cells also proliferate robustly 
     for more than 20 passages before undergoing senescence but 
     grow slowly in human ES cell culture conditions, a difference 
     that provides a proliferative advantage to reprogrammed 
     clones and aids in their selection by morphological criteria 
     (compact colonies, high nucleus to cytoplasm ratios, and 
     prominent nucleoli) alone (14, 15). IMR90 cells were 
     transduced with a combination of OCT4, SOX2, NANOG, and 
     LIN28. Colonies with a human ES cell morphology (iPS 
     colonies) first became visible after 12 days 
     posttransduction. On day 20, a total of 198 iPS colonies were 
     visible from 0.9 million starting IMR90 cells whereas no iPS 
     colonies were observed in non-

[[Page S14823]]

     transduced controls. Forty-one iPS colonies were picked, 35 
     of which were successfully expanded for an additional three 
     weeks. Four clones (iPS(IMR90)1-4) with minimal 
     differentiation were selected for continued expansion and 
     detailed analysis.
       Each of the four iPS(IMR90) clones had a typical human ES 
     cell morphology (Fig. 1B) and a normal karyotype at both 6 
     and 17 weeks of culture (Fig. 2A). Each iPS(IMR90) clone 
     expressed telomerase activity (Fig. 2B) and the human ES 
     cell-specific cell surface antigens SSEA-3, SSEA-4, Tra-1-60 
     and Tra-1-81 (Fig. 2C) whereas the parental IMR90 cells did 
     not. Microarray analyses of gene expression of the four 
     iPS(IMR90) clones confirmed a similarity to five human ES 
     cell lines (H1, H7, H9, H13 and H14) and a dissimilarity to 
     IMR90 cells (Fig. 3, table S3, and fig. S4). Although there 
     was some variation in gene expression between different 
     iPS(IMR90) clones (fig. S5), the variation was actually less 
     than that between different human ES cell lines (Fig. 3A and 
     table S3). For each of the iPS(IMR90) clones, the expression 
     of the endogenous OCT4 and NANOG was at levels similar to 
     that of human ES cells, but the exogenous expression of these 
     genes varied between clones and between genes (Fig. 3B). For 
     OCT4, some expression from the transgene was detectable in 
     all of the clones, but for NANOG, most of the clones 
     demonstrated minimal exogenous expression, suggesting 
     silencing of the transgene during reprogramming. Analyses 
     of the methylation status of the OCT4 promoter showed 
     differential methylation between human ES cells and IMR90 
     cells (fig. S6). All four iPS(IMR90) clones exhibited a 
     demethylation pattern similar to that of human ES cells 
     and distinct from the parental IMR90 cells. Both embryoid 
     body (fig. S7) and teratoma formation (Fig. 4) 
     demonstrated that all four of the reprogrammed iPS(IMR90) 
     clones had the developmental potential to give rise to 
     differentiated derivatives of all three primary germ 
     layers. DNA fingerprinting analyses (short tandem repeat-
     STR) confirmed that these iPS clones were derived from 
     IMR90 cells and confirmed that they were not from the 
     human ES cell lines we have in the laboratory (table S4). 
     The STR analysis published on the ATCC website for IMR90 
     cells employed the same primer sets and confirms the 
     identity of the IMR90 cells used for these experiments. 
     The iPS(IMR90) clones were passaged at the same ratio 
     (1:6) and frequency (every 5 days) as human ES cells, had 
     doubling times similar to that of the human H1 ES cell 
     line assessed under the same conditions (table S5), and as 
     of this writing, have been in continuous culture for 22 
     weeks with no observed period of replicative crisis. 
     Starting with an initial 4 wells of a 6-well plate of iPS 
     cells (one clone/well, approximately 1 million cells), 
     after 4 weeks of additional culture, 40 total 10-cm dishes 
     (representing approximately 350 million cells) of the 4 
     iPS(IMR90) clones were cryopreserved and confirmed to have 
     normal karyotypes.
       Since IMR90 cells are of fetal origin, we next examined 
     reprogramming of postnatal fibroblasts. Human newborn 
     foreskin fibroblasts (ATCC, Catalog No. CRL-2097) were 
     transduced with OCT4, SOX2, NANOG, and LIN28. From 0.6 
     million foreskin fibroblasts, we obtained 57 iPS colonies. No 
     iPS colonies were observed in non-transduced controls. 
     Twenty-seven out of 29 picked colonies were successfully 
     expanded for three passages, four of which (iPS(foreskin)-l 
     to 4) were selected for continued expansion and analyses. DNA 
     fingerprinting of the iPS(foreskin) clones matched the 
     fingerprints for the parental fibroblast cell line published 
     on the ATCC website (table S4).
       Each of the four iPS(foreskin) clones had a human ES cell 
     morphology (fig. S8A), had a normal karyotype (fig. S8B), and 
     expressed telomerase, cell surface markers, and genes 
     characteristic of human ES cells (Figs. 2 and 3 and fig. S5). 
     Each of the four iPS(foreskin) clones proliferated robustly, 
     and as of this writing, have been in continuous culture for 
     14 weeks. Each clone demonstrated multilineage 
     differentiation both in embryoid bodies and teratomas (figs. 
     S9 and S10); however, unlike the iPS(IMR90) clones, there was 
     variation between the clones in the lineages apparent in 
     teratomas examined at 5 weeks. In particular, neural 
     differentiation was common in teratomas from iPS(foreskin) 
     clones 1 and 2 (fig. S9A), but was largely absent in 
     teratomas from iPS(foreskin) clones 3 and 4. Instead, 
     there were multiple foci of columnar epithelial cells 
     reminiscent of primitive ectoderm (fig. S9D). This is 
     consistent with the embryoid body data (fig. Sl0), where 
     the increase in PAX6 (a neural marker) in iPS(foreskin) 
     clones 3 and 4 was minimal compared to the other clones, a 
     difference that correlated with a failure to downregulate 
     NANOG and OCT4. A possible explanation for these 
     differences is that specific integration sites in these 
     clones allowed continued high expression of the lentiviral 
     transgenes, partially blocking differentiation.
       PCR for the four transgenes revealed that OCT4, SOX2, and 
     NANOG were integrated into all four of the iPS(IMR90) clones 
     and all four of the iPS(foreskin) clones, but that LIN28 was 
     absent from one iPS(IMR90) clone (#4) and from one 
     iPS(foreskin) clone (#1) (Fig. 2D). Thus, although LIN28 can 
     influence the frequency of reprogramming (Fig. 1A), these 
     results confirm that it is not absolutely required for the 
     initial reprogramming, nor is it subsequently required for 
     the stable expansion of reprogrammed cells.
       The human iPS cells described here meet the defining 
     criteria we originally proposed for human ES cells (14), with 
     the significant exception that the iPS cells are not derived 
     from embryos. Similar to human ES cells, human iPS cells 
     should prove useful for studying the development and function 
     of human tissues, for discovering and testing new drugs, and 
     for transplantation medicine. For transplantation therapies 
     based on these cells, with the exception of autoimmune 
     diseases, patient-specific iPS cell lines should largely 
     eliminate the concern of immune rejection. It is important to 
     understand, however, that before the cells can be used in the 
     clinic, additional work is required to avoid vectors that 
     integrate into the genome, potentially introducing mutations 
     at the insertion site. For drug development, human iPS cells 
     should make it easier to generate panels of cell lines that 
     more closely reflect the genetic diversity of a population, 
     and should make it possible to generate cell lines from 
     individuals predisposed to specific diseases. Human ES cells 
     remain controversial because their derivation involves the 
     destruction of human preimplantation embryos and iPS cells 
     remove this concern. However, further work is needed to 
     determine if human iPS cells differ in clinically significant 
     ways from ES cells.
                                  ____


                               Exhibit 2

              Dolly Creator Prof Ian Wilmut Shuns Cloning

                          (By Roger Highfield)

       The scientist who created Dolly the sheep, a breakthrough 
     that provoked headlines around the world a decade ago, is to 
     abandon the cloning technique he pioneered to create her.
       Prof Ian Wilmut's decision to turn his back on 
     ``therapeutic cloning'', just days after US researchers 
     announced a breakthrough in the cloning of primates, will 
     send shockwaves through the scientific establishment.
       He and his team made headlines around the world in 1997 
     when they unveiled Dolly, born July of the year before.
       But now he has decided not to pursue a licence to clone 
     human embryos, which he was awarded just two years ago, as 
     part of a drive to find new treatments for the devastating 
     degenerative condition, Motor Neuron disease.
       Prof Wilmut, who works at Edinburgh University, believes a 
     rival method pioneered in Japan has better potential for 
     making human embryonic cells which can be used to grow a 
     patient's own cells and tissues for a vast range of 
     treatments, from treating strokes to heart attacks and 
     Parkinson's, and will be less controversial than the Dolly 
     method, known as ``nuclear transfer.''
       His announcement could mark the beginning of the end for 
     therapeutic cloning, on which tens of millions of pounds have 
     been spent worldwide over the past decade. ``I decided a few 
     weeks ago not to pursue nuclear transfer,'' Prof Wilmut said.
       Most of his motivation is practical but he admits the 
     Japanese approach is also ``easier to accept socially.''
       His inspiration comes from the research by Prof Shinya 
     Yamanaka at Kyoto University, which suggests a way to create 
     human embryo stem cells without the need for human eggs, 
     which are in extremely short supply, and without the need to 
     create and destroy human cloned embryos, which is bitterly 
     opposed by the pro life movement.
       Prof Yamanaka has shown in mice how to turn skin cells into 
     what look like versatile stem cells potentially capable of 
     overcoming the effects of disease.
       This pioneering work to revert adult cells to an embryonic 
     state has been reproduced by a team in America and Prof 
     Yamanaka is, according to one British stem cell scientist, 
     thought to have achieved the same feat in human cells.
       This work has profound significance because it suggests 
     that after a heart attack, for example, skin cells from a 
     patient might one day be manipulated by adding a cocktail of 
     small molecules to form muscle cells to repair damage to the 
     heart, or brain cells to repair the effects of Parkinson's. 
     Because they are the patient's own cells, they would not be 
     rejected.
       In theory, these reprogrammed cells could be converted into 
     any of the 200 other type in the body, even the collections 
     of different cell types that make up tissues and, in the very 
     long term, organs too. Prof Wilmut said it was ``extremely 
     exciting and astonishing'' and that he now plans to do 
     research in this area.
       This approach, he says, represents, the future for stem 
     cell research, rather than the nuclear transfer method that 
     his large team used more than a decade ago at the Roslin 
     Institute, near Edinburgh, to create Dolly.
       In this method, the DNA contents of an adult cell are put 
     into an emptied egg and stimulated with a shock of 
     electricity to develop into a cloned embryo, which must be 
     then dismantled to yield the flexible stem cells.
       More than a decade ago, biologists though the mechanisms 
     that picked the relevant DNA code that made a cell adopt the 
     identity of skin, rather than muscle, brain or whatever, were 
     so complex and so rigidly fixed that it would not be possible 
     to undo them.
       They were amazed when this deeply-held conviction was 
     overturned by Dolly, the first mammal to be cloned from an 
     adult cell, a feat with numerous practical applications, most 
     remarkably in stem cell science.
       But although ``therapeutic cloning'' offers a way to get a 
     patient's own embryonic stem cells to generate unlimited 
     supplies of cells

[[Page S14824]]

     and tissue there is an intense search for alternatives 
     because of pressure from the pro-life lobby, the opposition 
     of President George W Bush and ever present concerns about 
     cloning babies.
       Prof Wilmut's decision signals the lack of progress in 
     extending his team's pioneering work on Dolly to humans.
       The hurdles seem to have been overcome a few years ago by a 
     team led by Prof Hwang Woo-Suk in South Korea, with whom he 
     set up a collaboration.
       Then it was discovered Prof Hwang's work was fraudulent. 
     ``We spent a long time talking to him before discovering it 
     was all a fraud,'' he said. ``I never really got started 
     again after that.''
       And Prof Wilmut believes there is still a long way to go 
     for therapeutic cloning to work, despite the headlines 
     greeting this week's announcement in Nature by Dr Shoukhrat 
     Mitalipov and colleagues at Oregon Health & Science 
     University, Beaverton, that they cloned primate embryos.
       In all Dr Mitalipov used 304 eggs from 14 rhesus monkeys to 
     make two lines of embryonic stem cells, one of which was 
     chromosomally abnormal. Dr Mitalipov himself admits the 
     efficiency is low and, though his work is a ``proof of 
     principle'' and the efficiency of his methods has improved, 
     he admits it is not yet a cost effective medical option.
       Cloning is still too wasteful of precious human eggs, which 
     are in great demand for fertility treatments, to consider for 
     creating embryonic stem cells. ``It is a nice success but a 
     bit limited,'' commented Prof Wilmut. ``Given the low 
     efficiency, you wonder just how long nuclear transfer will 
     have a useful life.''
       Nor is it clear, he said, why the Oregon team was 
     successful, which will hamper attempts to improve their 
     methods. Instead, Prof Wilmut is backing direct reprogramming 
     or ``de-differentiation'', the embryo free route pursued by 
     Prof Yamanaka, which he finds ``100 times more interesting.''
       ``The odds are that by the time we make nuclear transfer 
     work in humans, direct reprogramming will work too.
       I am anticipating that before too long we will be able to 
     use the Yamanaka approach to achieve the same, without making 
     human embryos. I have no doubt that in the long term, direct 
     reprogramming will be more productive, though we can't be 
     sure exactly when, next year or five years into the future.''
       Prof Yamanaka's work suggests the dream of converting adult 
     cells into those that can grow into many different types can 
     be realised remarkably easily.
       When his team used a virus to add four genes (called Oct4, 
     Sox2, c-Myc and KIf4) into adult mouse fibroblast cells they 
     found they could find resulting embryo-like cells by sifting 
     the result for the one in 10,000 cells that make proteins 
     Nanog or Oct4, both typical markers of embryonic cells.
       When they studied how genes are used in these reprogrammed 
     cells, ``called induced pluripotent stem (iPS) cells'', they 
     were typical of the activity seen in an embryo. In the test 
     tube, the new cells look and grow like embryonic stem cells.
       And they were also able to generate viable chimaeras from 
     the cells, where the embryo cells created by the new method 
     could be mixed with those of a mouse embryo to grow into a 
     viable adult which could pass on the DNA of the reprogrammed 
     cells to the next generation.
       Nonetheless, there will have to be much work to establish 
     that they behave like embryo cells, let alone see if they are 
     safe enough to use in the body. Even so, in the short term 
     they will offer an invaluable way to create lines of cells 
     from people with serious diseases, such as motor neuron 
     disease, to shed light on the mechanisms.
       Given the history of fraud in this field, the Oregon 
     research was reproduced by Dr David Cram and colleagues at 
     Monash University, Melbourne. ``At this stage, nuclear 
     transfer to create pluripotent stem cell lines remains an 
     inefficient process,'' said Dr Cram.

  Mr. BROWNBACK. Mr. President, I suggest the absence of a quorum.
  The PRESIDING OFFICER. The clerk will call the roll.
  The legislative clerk proceeded to call the roll.
  Mr. CRAIG. Mr. President, I ask unanimous consent that the order for 
the quorum call be rescinded.
  The PRESIDING OFFICER (Mr. Salazar). Without objection, it is so 
ordered.
  Mr. CRAIG. Mr. President, let me inquire, we are in morning business?
  The PRESIDING OFFICER. The Senator is correct.

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