Testimony

• Dr. Laurie Zoloth
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  Testimony

  Dr. Laurie Zoloth

  Mr. Chairman, Senators: My name is Laurie Zoloth, and I am a professor of bioethics and religion in the Medical Humanities and Bioethics program, and director of bioethics at the Center for Genetic Medicine at the Feinberg School of Medicine, Northwestern University in Illinois. I want to thank the committee for asking us to testify about the ethical issues in human embryonic cell research, and tell you why my University and many of the organizations in which I serve—the Howard Hughes Medical Institute, the International Society for Stem Cell Research, the AAAS, the NAS, support and encourage human embryonic stem cell research. First, for it is part of our broad commitment to the translation of basic medical research into the great moral enterprise of healing—serving the public’s health is the core moral gesture of the medicine we teach. Second, we support stem cell research as a free academic activity, like free speech, that must be protected and sustained in our University and that must be both funded and regulated in full view of the public. As I wrote this speech, my 10th grader was also writing a speech about stem cells—I note this not tangentially, nor merely to remind that I am a mother of five, and I, like each of you, worry about the sort of moral universe I will leave to my children, but to stress how central this debate has become in our American democracy—it is the subject of how we speak of healing and our duty to heal, and it is the subject when we speak of human dignity, and it is how we express our hope and our fear of the future. Stem cells are important in this way because of the serious rumor of hope they carry for millions of yearning patients and families. As an early watcher of the science of stem cells, I have listened carefully to the excitement of the researchers, and while ethicists urge caution and avoid hyperbolic claims, most ethicists are convinced that the sincerity and veracity of a growing body of evidence about how these cells can be coaxed into useful tissue, and how these cells can explain the very nature of how cells grow, change and divide and die—in short, how disease plays out at the cellular level—is stunningly important. If even some of what we are told to hope for is correct, then how we think about illness and injury will be transformed. So why do ethical considerations stop full funding of this science? I would argue that there are three issues: where we get the cell, how we get the cell and what we use them for. First, is the issue of the origins of the cells, which means the moral status of the human blastocyst—can we destroy blastocysts, made in the lab, for any purpose? Can we do it for medical research and why or why not? Second is the process that researchers need to get eggs and sperm donated fairly and safely and responsibly, and handled with dignity. How are women’s special needs protected? How do we protect human subjects in the first stages of this research? Finally, if researchers can find successful therapies, how will good goals of medicine be protected, and access to the therapies be fair? Can we come to agreement on the proper ends of medicine? Stem cells are interesting to ethicists for precisely the same reason that they are intriguing to the market--they represent a therapeutic intervention that, unlike heart transplants, could be universally available, replicable and scaleable. If the daunting problems of histocompatibility can be overcome, embryonic stem cells could be made universally acceptable to any body. Unlike adult stem cells, which would have to be created each time for each particular user, the premise of application is the wide use. Bioethicists defend high intensity interventions like organ transplant, which have saved, albeit at high cost, thousands of individuals. But organ transplants are terribly expensive, and always rationed, and the risks considerable. Stem cell research is aimed at a wider community of vulnerable patients, and at no one particular category, age, ethnicity, or class. The sort of injury and diseases that stem cells are indicated for are not boutique, or rare--cell death and cell growth is at the core of nearly all disorders. Research into these essential causes would be precisely the sort of research we ought to insist on. Further, understanding how embryonic cells are programmed and reprogrammed might allow us to understand how to de-program cells, allowing adult cells to regenerate, teaching the body to heal itself. The demand for justice and the scrutiny to which genetic medicine is given are indications that we understand the power of genetics to reconfigure the self, and the society--in this way, the very debate about stem cells forces precisely the justice considerations that I would argue must be a part of medicine. The principle of justice places a priority on the public aspects of research--on public funding and on public oversight review boards for protocols. I think we can come to some agreement—around the duties of just medicine, and just science, and we have in the past come to agree on the how we must treat human research subjects and regulate that process, but I think we cannot come to some sort of agreement on what most divides us today—when human life begins, for this is a profoundly religious question in a profoundly religious country, profoundly dedicated to the proposition the our freedom to faithfully interpret our faith is the core of American life. For nearly all Jews, most Muslims, many Buddhists, and many Protestants, it is not only permissible to use human blastocysts to create stem cell lines, it is morally imperative—it must be done if it can lead to saving lives or healing. As an orthodox Jew, I understand the blastocyst, made in the lab, at the very first stages of division, prior to the time it could even successfully be transferred to a women’s body as just what it is at that moment: a cluster of primitive cells. It does not have the moral status of a human child—it lacks a mother’s womb, it existence is only theoretical without this, and even in the course of a normal pregnancy a blastocyst at 3 days is far before our tradition considers it a human person. While I respect that this is a difference in theology, and while I understand the passion and the conviction of those for whom the blastocyst is a person from the moment of fertilization, I do not believe this, and it is matter of faith for me as well. My passion and my conviction are toward the suffering of the one I see in need, ill, or wounded—for Jews and Muslims, the commandment to attend to this suffering is core to our faiths. Jewish organizations from Hadassah to the rabbinic and lay boards of all national Jewish denominations speak in one voice on this matter: human embryonic stem cell research is an activity of pekuah nefesh, saving and healing broken lives, and of tikkun olam—repairing an unfinished natural world. What are you to do, as leaders of our polity when we will not compromise faith positions? I suggest we must learn to compromise our faith policies—we do for other deeply felt issues and we must in this case as well. For example: we did not agree when life ended, but when heart transplants became a possibility, Harvard convened a committee to set criteria for “brain death” –an imperfect, biologically ragged, but useable compromise that allowed transplant research to develop. The US leads the world in successful transplant surgical techniques—and yet some faiths do not agree on these criteria. We do not agree on prenatal diagnosis, yet this is widely done, as is IVF even if it means embryos are destroyed to get one successful pregnancy. We do not agree, but we publicly fund and publicly go forward with research about these polices and we allow each family and physician to make private choices. We do this by a combination of courage and compromise—you shape our policy in different ways: Republicans in one way, Democrats in another, but both allow for research to go forward with limits, based in time, or geography. Now it is time to revisit these limits. In the last six month, I have traveled to three countries to look at their stem cell research and meet with their scientists: Israel, England and Korea. In each of these places, I also met with the bioethicists, philosophers, legal scholars and theologians who reflect on the research—who have demanded the same sort of careful, national, and public oversight I would think ethically important. What I saw was impressive—and for this committee in particular, critical. I saw that these countries understood that basic research in biology would be a core driver of their economy, that the knowledge, wisdom and energy that inspired that research would open the door to a world of new possibilities, some false starts, to be sure, but perhaps-just perhaps—some new starts. These countries understand that turning their full attention to science is not only prudent in our competitive global world, it is compassionate—it is the right thing to do to shape your country’s future toward healing the needs of the suffering. In South Korea’s labs, they meet at dawn to begin the work every single day, working with the same passion and government support we give to our Mars Rover programs, for example. Ought we to tremble when we cross such a threshold of human knowledge? Ought we to worry that we may be going too far or too fast? Of course, for we are being asked to understand the world differently, the self differently, what it means to be human and to be unique, differently—to know and to see things which were impossible to know or see a decade ago. Of course we need to think soberly about the possibility that the research may fail utterly, or that it may succeed but lead us into a place of great unpredictability—that is the very nature of research—that is why the future is what makes us free, this uncertainty. Courage to face the problem will mean a compromise that can be regulated, as we did with recombinant DNA, as we did in organ transplantation. I would urge a far broader and more open policy than our American scientist face now, for it is far too late to stop, ban, or have a moratorium on the basic science of human embryonic stem cells—it not only will proceed, it has proceeded, in Asia, Israel, Europe and England. Stem cell research will now clearly be a possible road. Where that road might turn us is unknown—but what is certain is that if we turn off the road, we will watch others pass us by. Our challenge- and this means each of us—scientist, citizen, congregant, critics and enthusiast—most of all Senator—will be how to live bravely and decently and fairly in a complex world of difficult moral choices. Can stem cell research yield therapies that could help millions who now suffer? Will it yield cures for diabetes, Parkinson’s, spinal cord injury? Who can yet know? If it were able to help even some, that might be light enough in the storm filled world. I tell my son that he must raise these questions, the core questions of ethics and of biology--How are we human? How will we be free? What must I do about the suffering of the other person? And that stem cell science can remind us that we are most human when we act as healers, we are the most free when we explore what we don’t yet know, and we are bound to a duty to shape our work to care always for the person in need. Thank you.

• Mr. Richard Doerflinger
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  Testimony

  Mr. Richard Doerflinger

  I am Richard M. Doerflinger, Deputy Director of the Secretariat for Pro-Life Activities at the U.S. Conference of Catholic Bishops. On behalf of the bishops’ conference I want to thank this Subcommittee for asking us to present our views on the ethics of human embryonic stem cell research. I. The Need for Ethical Safeguards in Human Research The central ethical issue raised by this research is raised whenever proponents of unlimited research freedom complain that ethical restraints get in the way of “progress.” This tension between technical advance and respect for research subjects is at least as old as modern medicine itself. As soon as Western thinkers began to see medicine as a science that could advance and acquire new knowledge, the temptation arose of using human beings as mere means to this end. When Dr. Claude Bernard sounded an alarm against this temptation in the 19th century, the preferred victims were prisoners convicted of serious crimes. He insisted that the physician must not deliberately do harm to any human being simply to acquire knowledge that may help others: The principle of medical and surgical morality, therefore, consists in never performing on man an experiment that might be harmful to him to any extent, even though the result might be highly advantageous to science, i.e., to the health of others. But performing experiments and operations exclusively from the point of view of the patient’s own advantage does not prevent their turning out profitably to science. In 1865, Dr. Bernard was already making the important distinction between therapeutic and nontherapeutic experimentation. The fact that an experiment may benefit the research subject is only one moral requirement among others; but it is one thing to provide a human being with an experimental treatment whose outcome may also help in treating others in the future, and quite another thing simply to use him or her as a means, imposing significant risk of harm on him or her solely to benefit others. In the Nuremberg Code, the United States and its allies responded to the horrors of the Nazi war crimes by restating this principle, to ensure that human dignity would not again be trampled on in the pursuit of medical knowledge. Among other things, the Code declared: “No experiment should be conducted where there is an a priori reason to believe that death or disabling injury will occur...” This Code inspired many later declarations, including the “Declaration of Helsinki” first approved by the World Medical Association in 1964. Here the key principle is: In medical research on human subjects, considerations related to the well-being of the human subject should take precedence over the interests of science and society. The Helsinki declaration noted that this principle must apply to all human beings, and that “some research populations,” including those who cannot give consent for themselves, “need special protection.” It seems this principle was intended to encompass the unborn, as the same organization’s statement on the ethics of the practicing physician, the “Declaration of Geneva,” had the physician swear that “I will maintain the utmost respect for human life, from the time of conception.” Despite these solemn declarations, American scientists and others dazzled by visions of technical progress have always been tempted to endorse a utilitarian approach to ethics, and to treat helpless or unpopular members of the human race as mere means to their ends. In the Tuskegee syphilis experiment, for example, hundreds of poor black sharecroppers were deliberately left with untreated syphilis for over twenty years to observe the course of their disease. This was no isolated aberration but a sustained, decades-long study conducted with U.S. government support. A report filed by the Public Health Service at the end of the process, in 1953 (years after Nuremberg!), shows no trace of ethical concern — rather, the authors comment favorably on how subjects were encouraged to comply with the study by the offering of “incentives” — including the offer of free burial assistance once they died from their untreated syphilis! The authors concluded: “As public health workers accumulate experience and skill in this type of study, not only should the number of such studies increase, but a maximum of information will be gained from the efforts expended.” There were indeed more such studies. We need only think of the study at Willowbrook children’s home, where retarded children in the 1960s were deliberately injected with hepatitis virus to study ways of preventing spread of the disease. One justification offered by the researchers was that hepatitis was so common in the institution that these children probably would have been exposed to it anyway — an argument we now see in the embryo research debate, when researchers insist that the human embryos they destroy probably would have been discarded anyway. Or we can look to our government’s Cold War studies on the effects of radiation using unsuspecting military and civilian subjects, conducted from the 1940s to the 1970s — where the drive to pursue knowledge could claim additional support from the drive for national security. The same utilitarian approach drives those who seek to justify harmful experiments on human embryos today. When asked in 1994 whether the National Institutes of Health’s Human Embryo Research Panel should base its conclusions on the principle that “the end justifies the means,” the Panel’s chief ethicist quoted the man known as the father of situation ethics, Joseph Fletcher: “If the end doesn’t justify the means, what does?” This ethicist later became the chief ethicist for Advanced Cell Technology, the Massachusetts biotechnology company most prominent in the effort to clone human embryos for research purposes. Interestingly, Fletcher himself claimed that the phrase originally came from Nikolai Lenin, who reportedly used it to justify the killing of countless men, women and children in the Russian revolution of 1917. History provides us with little reason to favor utilitarian thinking about human life -- for even judged by its own terms, making moral judgments solely on the basis of consequences has so often had terrible consequences. Because scientists, and the for-profit companies that increasingly support and make use of their research, are always tempted to treat helpless members of the human family as mere means to their ends, the rest of society – including government – must supply the urgently needed barrier against unethical exploitation of human beings. II. The Moral Status of the Human Embryo Some will object that one-week-old human embryos, uniquely among all classes of living human organisms, deserve no such protection from destructive experiments. They hold that these embryos, “according to science, bear as much resemblance to a human being as a goldfish.” But this is simply scientific ignorance. Modern embryology textbooks tell us that the initial one-celled zygote is “the beginning of a new human being,” and define the “embryo” as “the developing human during its early stages of development.” The continuity of human development from the very beginning, and the reality of the early embryo as a living organism of the human species, has been underscored by recent biological discoveries. Commenting on these new findings, a major science journal concluded that “developmental biologists will no longer dismiss early mammalian embryos as featureless bundles of cells.” Political groups may still attempt to do so, of course, but they cannot claim that science is on their side. While it makes no sense to say that any of us was once a body cell, or a sperm, or an egg, it makes all the sense in the world to say that each of us was once an embryo. For the embryo is the first stage of my life history, the beginning of my continuous development as a human organism. This claim makes the same kind of sense as the claim that I was once a newborn infant, although I do not have any recollection of cognitive or specifically human “experiences” during that stage of life. The principle that the embryo deserves recognition and respect as a member of the human family is also already reflected in numerous areas of federal law. At every stage of development, the unborn child in the womb is protected by federal homicide laws as a separate victim when there is a violent attack upon his or her mother. That same child is recognized in federal health regulations as an eligible patient deserving prenatal care. And of course, for the last eight years that same embryo has been protected, in much the same way as other human subjects, from being harmed or killed in federally funded research. Catholic moral teaching on this issue is very clear. Every human life, from the first moment of existence until natural death, deserves our respect and protection. Human life has intrinsic dignity, not only a relative or instrumental value; thus every living member of the human species, including the human embryo, must be treated with the respect due to a human person. We hold further that attempts to make a principled argument as to why embryos need not be respected as persons end up excluding many other members of the human race from this status as well. Any mental or physical ability or characteristic (aside from simple membership in the human race) that one may propose as the deciding factor for “personhood” will be lacking in some people, or held more by some people than by others. Thus Catholic morality regarding respect for human life, and any secular ethic in agreement with its basic premises, rejects all deliberate involvement with the direct killing of human embryos for research or any other purpose. Such killing is gravely and intrinsically wrong, and no promised beneficial consequences can lessen that wrong. This conviction is also held by many American taxpayers, who should not be forced by government to promote with their tax dollars what they recognize as a direct killing of innocent human persons. But even those who do not hold the human embryo to be a full-fledged human person can conclude that embryonic stem cell research is unethical. Many moral wrongs fall short of the full gravity of homicide but are nonetheless seriously wrong. Setting aside “personhood,” surely no one prefers funding research that requires destroying human life. Four major advisory groups recommending federal policies on human embryo research over the past 23 years have agreed that the destruction of human life is exactly what is at stake in research that involves destroying human embryos. For example, the Ethics Advisory Board to the Department of Health, Education and Welfare concluded in 1979 that the early human embryo deserves “profound respect” as a form of developing human life (though not necessarily “the full legal and moral rights attributed to persons”). The NIH Human Embryo Research Panel agreed in 1994 that “the preimplantation human embryo warrants serious moral consideration as a developing form of human life.” In 1999, the National Bioethics Advisory Commission (NBAC) cited broad agreement in our society that “human embryos deserve respect as a form of human life.” And in 2002, the National Academy of Sciences acknowledged that “in medical terms,” the embryo is a “developing human from fertilization” onwards. What does this respect mean, if it does not mean full and active protection from harm of the kind we extend to human persons? At a minimum, doesn’t it mean that we will not use public funds to promote such harm? It is absurd to treat a human life solely as a source of spare parts for other people, and claim that this demonstrates your “respect” for that life. It is equally absurd to fund stem cell research that encourages researchers to destroy human embryos for their cells, and claim that one is not promoting disrespect for the lives of those embryos. It does not help this argument to claim that the only embryos to be destroyed for research are those who “would have been discarded anyway.” The mere fact that some parents discard “excess” embryos creates no argument that the federal government should intervene to assist in their destruction – any more than the fact that many abortions are performed in the U.S. creates an argument that Congress must use its funding power to promote such killing. In fact, Congress has for many years rejected arguments that it can fund harmful experiments on unborn children slated for abortion because “they will die soon anyway.” See 42 USC §289g. The claim that humans who may soon die automatically become fodder for lethal experiments also has ominous implications for condemned prisoners and terminally ill patients. In the final analysis, all of us will die anyway, but that gives no one a right to kill us. Even on its own amoral terms, that argument also misunderstands the informed consent process for “disposition” of frozen embryos in U.S. fertility clinics. When these clinics produce more embryos in a given cycle than parents need for their immediate reproductive goals, they do indeed freeze the “excess” embryos and ask the parents what should be done with them after a given time. Most clinics offer the options of continuing to preserve the embryos, using them for further reproductive efforts by the couple, donating them to another couple for reproduction, discarding them, or donating them for research. But these are mutually exclusive options. For example, it would violate the professional code of the fertility industry to take embryos “to be discarded” and use them for research instead. And among embryos donated for research, no researcher or government official can tell which embryos “would have been discarded” if this option had not been offered. The problem with past federal advisory panels is that they have generally failed to give any real content to the notion of “respect” or “serious moral consideration” for the embryonic human. The NIH Human Embryo Research Panel failed miserably in this task. Since the Panel approved a wide array of lethal experiments on human embryos -- including some which required specially creating embryos solely to destroy them – even the Panel’s own members publicly observed that it had come to use the word “respect” merely as a “slogan” with no moral force. In the end, the Panel’s report was rejected in part by President Clinton (who denied funding for experiments involving the creation of embryos for research), and rejected in its entirety by Congress (which enacted the appropriations rider against funding harmful embryo research that remains in law to this day). Five years later, the National Bioethics Advisory Commission tried to give more definition to what “respect” for the embryo might mean in the research context: In our judgment, the derivation of stem cells from embryos remaining following infertility treatments is justifiable only if no less morally problematic alternatives are available for advancing the research. While this standard does not fully respect the embryo as a person with inviolable rights, it creates a presumption against research that requires killing embryos: Such research was to be a last resort, pursued only after it is found that research benefits cannot be pursued in any other way. However, the Commission then evaded the implications of this standard, by ignoring the emerging evidence about the promise of adult stem cells and other alternatives. But the Commission admitted that its factual claim on this point must be reevaluated as scientific knowledge advanced. As the National Institutes of Health acknowledged in 2001, the burden of proof needed to justify human embryo research by NBAC’s ethical standard has never been met. The NIH’s review of stem cell research concluded that any therapies based on embryonic stem cells were “hypothetical and highly experimental,” and that it could not be determined at that time whether these cells would have any advantages over the less morally problematic alternatives. Since that time, in fact, scientific and practical barriers to the medical use of embryonic stem cells have loomed larger than many scientists expected in 1999. Problems of tumor formation, uncontrollability, and genetic instability are now cited among the reasons why embryonic stem cells cannot safely be used in human trials any time in the foreseeable future. At the same time, non-embryonic stem cells have moved quickly into promising clinical trials for a wide array of conditions, including spinal cord injury, multiple sclerosis, Parkinson’s disease, heart damage and corneal damage. Many researchers and biotechnology companies have responded to this evidence by simply abandoning NBAC’s standard. In short, they are losing the game and have decided to move the goalpost. What is now often heard is that research using both embryonic and non-embryonic stem cells must be fully funded now, to determine which source is best for various functions. In other words, we must help researchers violate NBAC’s ethical standard now, to determine whether they will ever be able to meet the burden of proof that standard places on them. But this approach simply reduces “respect” for the embryo to nothing at all. For that is the approach one would take if there were no moral problem whatever -- if the only factor determining our research priorities were relative efficiency at achieving certain goals. “Respect” must mean, at a minimum, that we are willing to give up some ease and efficiency in order to obey important moral norms instead of transgressing them. At this point, it is not even established that continued pursuit of embryonic stem cell research would increase the ease and efficiency of arriving at any treatments, for it may only divert attention and resources away from alternative approaches that could cure diseases more quickly. In short, using federal funds to encourage the destruction of embryos for new stem cell lines not only fails the test of a principled “sanctity of life” ethic. Given the lack of clear evidence for any unique or irreplaceable role for embryonic stem cells in the treatment of devastating diseases, it even fails the test offered by proponents of human embryo research when they advised the federal government on this issue five years ago. III. The Reality of an Ethical Slippery Slope The campaign for expanded federal support for embryonic stem cell research also ignores the fact that its goal cannot be achieved without violating even more ethical norms. Any agenda that will inevitably require such further violations in order to produce any of its promised results must be held accountable now for justifying those violations. Otherwise our government could waste years of effort and millions of dollars on an approach that must be abandoned in midstream, before producing results – with devastating consequences for patients now awaiting treatments. At present, contrary to many misleading comments in the political debate, there are no set limits on the amount of federal funding that may be allocated for embryonic stem cell research. However, current policy is to fund only research using the embryonic stem cells obtained by destroying human embryos prior to August 9, 2001. These cell lines are intended to be adequate only for basic research, to determine whether embryonic stem cells offer uniquely promising benefits without encouraging the destruction of live embryos to obtain the cells for that project. Some claim the currently eligible cell lines are inadequate in number and “contaminated” by the mouse feeder cells used to culture them. They argue that new cell lines like those recently created with private funds by Harvard researchers, and the “more than 400,000 IVF embryos” now frozen that could be used for research, must not be allowed to go to waste. The implied argument is that if only these additional cell lines, and currently existing “excess” embryos, were offered up for federally funded research, researchers would have all they need to cure terrible diseases. But even if embryonic stem cells could ever be used to cure serious illnesses – which at this point is hypothetical – this argument makes no sense. It is important to understand why. First, it has not been shown that the cell lines already eligible for funding are inadequate for their intended task -- conducting basic research in the advantages and disadvantages of these cells. Because some of the cells were frozen for later use immediately after being harvested from embryos, the number of actual cell lines continues to grow as the cells are thawed and cultured. For example, there were 15 lines when House members wrote to President Bush urging an expanded policy this summer, and 19 by the time the Senate letter was circulated a few weeks later. According to the NIH, over 400 derivatives of these lines have been shipped to researchers as of February 2004. Some cells remain frozen at this point (and so could be cultured without the ‘contamination” of animal feeder cells if necessary), while over two dozen eligible cell lines are currently unavailable to federally funded researchers only because their owners have not yet agreed to share them with other researchers. Second, the new Harvard cell lines have the same deficiencies as the currently eligible cell lines. They are inadequate for any significant clinical use, they were cultured in mouse feeder cells, and – most interesting of all – they have already developed serious genetic “abnormalities” in culture. A recent study suggests that all human ESC lines may spontaneously accumulate extra chromosomes that are typical of human embryonal carcinoma cells from testicular cancer. Third, the Rand study which concluded that there may be as many as 400,000 frozen embryos in the United States also found that only 11,000 (less than 3% of the total) are designated by parents for possible use in research. If all these 11,000 frozen embryos were destroyed for their stem cells (seen by the authors as a “highly unlikely”scenario), this may produce a grand total of 275 cell lines – surely inadequate for use in treating any major disease. Last year an opinion piece attacking President Bush’s policy cited two prominent researchers in support of the claim that merely determining the “best options for research” (to say nothing of clinical use) would require “perhaps 1,000” stem cell lines -- about four times as many as those which could be obtained by destroying every available human embryo in frozen storage nationwide. Another group of researchers has concluded that in order to reflect the genetic and ethnic diversity of the American population, an embryonic stem cell bank geared toward treating any major disease would have to include cell lines from many embryos created solely in order to be destroyed for those cells – including a disproportionate number of specially created embryos conceived by black couples and other racial minorities, who are underrepresented among current fertility clinic clients. Yet another prominent stem cell researcher estimated that unless researchers resort to human cloning to produce genetically matched stem cells for each patient, “millions” of embryos from fertility clinics may be needed to create cell lines of sufficient genetic diversity for clinical use. Of course, trying to address this problem with cloning would require specially creating and then destroying many millions of embryos as well – an estimated hundred embryos per individual patient, potentially requiring the exploitation of many millions of women for their eggs to treat even one major disease. Undaunted, the national Biotechnology Industry Organization (BIO), in a statement echoed by many researchers, has testified that the use in humans of the cloning technique that created Dolly the sheep will be “essential” to realizing the promise of embryonic stem cell research. BIO’s testimony on this point should help to clarify our minds, for it may be rephrased as follows: Unless you are willing to commit yourself in the future to human cloning and the mass-production of human lives in order to exploit and destroy them, there is no point in promoting federally funded research using so-called “excess” embryos now. And there is yet another moral line to cross beyond this. For the effort to use human embryo cloning for “therapeutic” purposes involves all the practical barriers inherent in embryonic stem cell research in general, plus some additional problems. For example, even cloned embryos with a normal genetic makeup generally suffer from chaotic gene expression, leading to many embryonic and fetal deaths and to increased risks in using any cells from these embryos for future therapies. There is evidence that there may be a later opportunity in fetal development to correct these gene expression problems, if the embryo can survive to that point. Perhaps due partly to this phenomenon, the major studies seeking to provide an animal model for “therapeutic” cloning have found it necessary to implant the cloned embryo in a womb and develop it past the embryonic stage to obtain usable cells and tissues. Thus the old alleged distinction between “reproductive” cloning (placing cloned embryos in a womb for gestation) and “therapeutic” cloning (destroying cloned embryos for research purposes) is breaking down, as the former increasingly becomes a necessary component of the latter. BIO has already acted to provide legislative authorization for this approach in humans -- by supporting state laws to allow researchers to clone human embryos and develop them in wombs into the last stages of fetal development, as long as they do not allow a full-term live birth. One such law has already been enacted, in New Jersey. And the pending California ballot initiative known as Proposition 71, which would force the financially strapped state government to borrow $3 billion to fund embryonic stem cell and human cloning research, would “initially” forbid developing cloned human embryos past 12 days -- but allow indefinite expansion of this limit, by vote of a new Oversight Committee dominated by stem cell advocates. In short, no new breakthroughs have shown that embryonic stem cells are ready or almost ready for clinical use. Use of new cell lines from frozen embryos has not been shown to be necessary for current basic research, and would still be completely inadequate for any large-scale clinical research – suggesting that proposals for expanding the current embryonic stem cell policy are themselves only a transitional step toward mass-producing embryos (by cloning or other means) solely for harmful experimentation. The for-profit biotechnology industry has known this for years, and has begun paving the legislative road toward large-scale human cloning and “fetus farming” in case these prove necessary for technical progress in this field. Conclusion Since human embryonic stem cells were isolated and cultured in 1998, initial hyped promises of miracle cures for devastating diseases have collided with reality. More than two decades of research using mouse embryonic stem cells have produced no treatments in mice that are safe or effective enough for anyone to propose in humans. These cells have not helped a single human being, and the practical barriers to their safe and effective use loom larger than ever. Meanwhile, alternative approaches that harm no human being have moved forward to offer realistic hope for patients who many said could be helped only by research that destroys human embryos. Campaigns for increased public funding have grown in inverse proportion to the dwindling hopes of medical benefit, as private funding sources increasingly realize that embryonic stem cell research may not be a wise investment. We should not succumb to this latest campaign, but reflect on the ethical errors that brought us this far. Even proponents of the research have admitted that it poses an ethical problem, because it involves destroying human lives deserving our respect. Based in part on the actions and statements of proponents, we can see that still further ethical breaches will be required of Congress and society to realize the “promise” of this approach. Already the policy debate has moved from “spare” embryos in fertility clinics, to specially creating embryos for destruction, to mass-production of embryos through cloning, to the gestation of these embryos for “fetus farming” and the harvesting of body parts. Congress should take stock now and realize that the promise of this approach is too speculative, and the cost too high. That cost includes the early human lives destroyed now and in the future, the required exploitation of women for their eggs and perhaps for their wombs, and the diversion of finite public resources away from research avenues that offer real reasons for hope for patients with terrible diseases. Let’s agree to support avenues to medical progress that we can all live with.

Witness Panel 2

• Dr. George Daley
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  Witness Panel 2

  Dr. George Daley

  Senator Brownback, members of the Committee, thank you for inviting me here today to testify before you. My name is George Daley. I am here representing The American Society for Cell Biology where I serve as a member of the Public Policy Committee. The ASCB represents over 11,000 basic biomedical researchers in the United States and in 45 other countries. [For the record, I am Associate Professor of Pediatrics and Biological Chemistry at the Boston Children's Hospital and Harvard Medical School, Associate Director of the Children’s Hospital Stem Cell Program, a member of the Executive Committee of the Harvard Stem Cell Institute, a Board member of the International Society for Stem Cell Research, and chair of the Scientific Review Committee of the Stem Cell Research Foundation. I received one of the first grants issued by the NIH for the study of human embryonic stem cells.] I am a physician-scientist, board certified in Internal Medicine and Hematology and clinically active in the care of children and adults with malignant and genetic diseases of the blood and bone marrow. I run an NIH-supported laboratory that studies both adult and embryonic stem cells. Part of my lab focuses on the human disease Chronic Myeloid Leukemia, a cancer that arises from the adult blood stem cell. Part of my lab is investigating how to coax embryonic stem cells to differentiate into blood stem cells. My laboratory has succeeded in transplanting mice with blood stem cells derived entirely in vitro from embryonic stem cells. Our goal is to replicate this success using human embryonic stem cells, with the hope of someday treating patients with leukemia, immune deficiency, aplastic anemia, and genetic diseases like sickle cell anemia. As the title of the hearing states, controversy surrounds the field of human embryonic stem cell research. At the core of the controversy is the fact that harvesting embryonic stem cells requires the destruction of a human embryo. If you ascribe full personhood to the earliest stages of human development, then you are vigorously opposed to embryonic stem cell research and opposed to fertility treatments that generate embryos that are the source of embryonic stem cells. In contrast, if you believe that the earliest human embryos, as microscopic balls of primitive cells, are not the moral equivalents of babies, then you are likely to be equally vigorous in supporting embryonic stem cell research because of its immense promise for understanding and treating disease. These dueling perspectives are informed more by religious and moral beliefs than by scientific principles. However, scientific issues indeed play an important role in the current debate. As with most controversies, much misinformation exists. Today, I am here to offer scientific testimony to clarify the facts and dispel the myths surrounding competing claims in adult and embryonic stem cell research. I will address two central scientific questions: First, is research on human adult stem cells so promising that we need not pursue research with embryonic stem cells? Second, is the current Presidential policy that restricts researchers to only a limited set of cell lines created before August 9th, 2001 adequate to explore the potential of human embryonic stem cell research? The simple but emphatic answer to the first question is “no.” Although research on adult stem cells is enormously promising and has already yielded clinical success in the form of bone marrow transplantation, adult stem cells are not the biological equivalents of embryonic stem cells, and adult stem cells will not satisfy all scientific and medical needs. Moreover, a great many questions about adult stem cells remain unanswered. Adult stem cells have been unequivocally isolated from bone marrow, skin, and mesenchyme, but adult stem cells do not appear to exist for all tissues of the body. Claims of stem cells for the heart, pancreas, and kidney remain controversial. You will also hear claims that adult stem cells are plastic, perhaps as versatile as embryonic stem cells, and that success with adult stem cells obviates the need to study embryonic stem cells. As an expert in both adult and embryonic stem cell biology, I take issue with these claims. It is the nature of adult stem cells to regenerate only a limited subset of the body’s tissues. As best we can tell, under normal physiologic circumstances, adult stem cells do not have a measurable capacity to differentiate beyond their tissue of origin. Therefore, asking blood stem cells to regenerate heart or liver or brain is to ask adult stem cells to betray their intrinsic nature. Like cellular alchemy, attempts to engineer adult stem cell plasticity may never succeed in a clinically practical manner. I am not arguing we should not invest in some highly speculative realms of cellular engineering with adult stem cells. Indeed, we should. I am arguing however, that the promise of adult stem cells in no way obviates the need to investigate embryonic stem cells. Claiming that the study of adult stem cells should trump the study of embryonic stem cells is an opinion at the fringe and not the forefront of scientific thinking. While the differentiation spectrum of adult stem cells is restricted, it is an incontrovertible fact that embryonic stem cells have the ability to form all cells in the body. Such is the natural endowment of the stem cells of the early embryo, and the very reason they inspire such fascination among stem cell biologists. Scientists are seeking to discover the natural mechanisms that drive formation of specific cells and tissues, so that these principles can be faithfully reproduced with embryonic stem cells in the Petri dish. I would argue that coaxing embryonic stem cells to do what comes naturally to them is more likely to prove successful in the near term than reengineering adult stem cells towards unnatural ends. The American Society of Cell Biology and every other major scientific society supports the study of both adult and embryonic stem cells. To the second question, “Is the current Presidential policy adequate to explore the potential of human embryonic stem cell research?” I also answer an emphatic “no.” Today, federally-funded scientists operate under a restrictive policy that limits the human embryonic stem cells that can be studied to a modest number of lines generated over three years ago. With the pre-2001 vintage cell lines we can address generic questions, but are prohibited from exploiting the latest tools being developed around the Globe. It runs contrary to the American spirit of innovation for our government to deny its scientists every advantage to push the frontiers. Ultimately this will slow the pace of medical research, and compromise the next generation of medical breakthroughs. I recently published an article in the New England Journal of Medicine entitled “Missed opportunities in human embryonic stem cell research1”, in which I articulated the scientific avenues that are not being adequately investigated due to the current Presidential policy. In the three years since the President announced his policy, over a hundred additional lines have been generated, many with advantageous properties that make them highly valuable to medical scientists. Some of these new lines model diseases like cystic fibrosis, muscular dystrophy, and genetic forms of mental retardation. What does the President say to families whose children are affected by these devastating diseases? How does the President justify his lack of support for this research? Where is the compassion in such a policy? Thankfully, I am the father of two healthy boys, ages 3 and 6. I am taking great delight in teaching them baseball and watching them root for the Red Sox. (They have much to learn about heartache in the world). As a father, I count my blessings for these God-given gifts, more so every time I walk through the lobby of the Children’s Hospital, and see the many kids who will never run the bases or smack a home run. As a physician, I see the mission of ES cell research as providing the greatest hope to relieve the suffering I see in many of my patients. As a scientist, I am not impervious to the expressions of ethical concern for the sanctity of the human embryo. But in our religiously plural society, I fear we may never reach an ethical consensus given the competing entities in this debate: microscopic human embryos that represent incipient human life on the one hand, desperate patients suffering from debilitating diseases on the other. From my perspective as a father, physician, and scientist, I am moved by concern for my two boys, my patients, and for the life-affirming mission of hope and promise in embryonic stem cell research. 1) Daley GQ. Missed opportunities in embryonic stem-cell research. N Engl J Med 351:627-8, 2004.

• Dr. David Prentice
  Read statement

  Witness Panel 2

  Dr. David Prentice

  Mr. Chairman, Distinguished Members of the Committee, thank you for the opportunity to provide testimony on this important subject. Mark Twain noted that “There is something fascinating about science. One gets such wholesale returns of conjecture out of such a trifling investment of fact.” This is certainly true regarding the hype and emotion surrounding the stem cell issue. We should start with some biological definitions, to provide a common scientific frame of reference. “Almost all higher animals start their lives from a single cell, the fertilized ovum (zygote)... The time of fertilization represents the starting point in the life history, or ontogeny, of the individual.” The quotes below are from internationally preeminent human embryologist Ronan O’Rahilly in his latest textbook. Dr. O’Rahilly originated the international Carnegie Stages of Human Embryological Development, used for many decades now by the International Nomina Embryologica (now the Terminologica Embryologica) Committee which determines the scientifically correct terms to be used in human embryology around the world. “Although life is a continuous process, fertilization...is a critical landmark because, under ordinary circumstances, a new, genetically distinct human organism is formed when the chromosomes of the male and female pronuclei blend in the oocyte. This remains true even though the embryonic genome is not actually activated until 2-8 cells are present, at about 2-3 days... During the embryonic period proper, milestones include fertilization, activation of embryonic from extra-embryonic cells, implantation, and the appearance of the primitive streak and bilateral symmetry. Despite the various embryological milestones, however, development is a continuous rather than a saltatory process, and hence the selection of prenatal events would seem to be largely arbitrary.” “Prenatal life is conveniently divided into two phases: the embryonic and the fetal…[I]t is now accepted that the word embryo, as currently used in human embryology, means ‘an unborn human in the first 8 weeks’ from fertilization. Embryonic life begins with the formation of a new embryonic genome (slightly prior to its activation).” Thus whether within the body or in the laboratory via In vitro fertilization or other assisted reproductive techniques, the first stage of development of a new individual begins with fertilization. Because it has become an area of interest, it is useful to point out that biologically the process of cloning (somatic cell nuclear transfer; SCNT) also produces a zygote as the starting point for development. As the President’s Council on Bioethics has noted, “The first product of SCNT is, on good biological grounds, quite properly regarded as the equivalent of a zygote, and its subsequent stages as embryonic stages in development.” The National Academy of Sciences noted the following: “The method used to initiate the reproductive cloning procedure is called nuclear transplantation, or somatic cell nuclear transfer (SCNT). It involves replacing the chromosomes of a human egg with the nucleus of a body (somatic) cell from a developed human. In reproductive cloning, the egg is then stimulated to undergo the first few divisions to become an aggregate of 64 to 200 cells called a blastocyst. The blastocyst is a preimplantation embryo that contains some cells with the potential to give rise to a fetus and other cells that help to make the placenta. If the blastocyst is placed in a uterus, it can implant and form a fetus. If the blastocyst is instead maintained in the laboratory, cells can be extracted from it and grown on their own.” Embryonic stem cells can be isolated from a blastocyst-stage embryo early in human development, whether produced by fertilization or by cloning (SCNT): “[A]n embryonic stem cell (ES cell) is defined by its origin. It is derived from the blastocyst stage of the embryo. The blastocyst is the stage of embryonic development prior to implantation in the uterine wall.” A first question we might address is, “Why use stem cells?” The short answer is to treat degenerative diseases. In the past, infectious diseases were the scourge of mankind; antibiotics, vaccinations, and sanitation have dealt with these as killers. Today degenerative diseases, such as heart disease, stroke, chronic lung disease, Parkinson’s disease, and diabetes are our main concern. These leading causes of death in the U.S. are common to all developed nations and are becoming more prevalent in developing nations. In degenerative diseases, it is usually only part of the organ or tissue that is damaged, rather than the entire organ. Stem cells are proposed to treat these diseases by repairing and replacing the damaged tissue. A stem cell has two chief characteristics: (1) it multiplies, maintaining a pool of stem cells, and (2) given the correct signal, it can differentiate into other specific cell types for use by the body. There are several sources of stem cells (see figure above). The two types which have generated the most interest are embryonic stem cells derived from the early embryo (5-7 days after conception), and so-called adult stem cells which reside in most, if not all, tissues of the body. Embryonic stem cells were first isolated in mice in 1981, and in humans in 1998; adult stem cells were first identified in bone marrow in the 1960’s, and in recent years have been found in a wide range of tissues throughout the body. Adult stem cells are actually present in the tissues of the individual from the moment of birth, and could more properly be termed tissue stem cells, post-natal stem cells, or non-embryonic stem cells, and include umbilical cord blood stem cells and placental stem cells. Embryonic stem cells are derived by removing the inner cell mass of the early human embryo (the blastocyst); in this process, the embryo is destroyed. The cells are placed into culture, and their purported advantages are that they can proliferate indefinitely, and can form any tissue. Scientific publications support the claim that they can proliferate for long periods of time in culture. In theory they can form any tissue; however, the experimental basis of their potential to form any tissue relies on the cells being within the normal developmental context of the embryo, where they form the range of tissues and organs of the human body during normal development. While embryonic stem cells might seem to have a theoretical advantage over adult stem cells, the published literature shows that the claims for embryonic stem cell advantages over adult stem cells are thus far unsubstantiated. Indeed, the National Institutes of Health has noted that: “Thus, at this stage, any therapies based on the use of human ES cells are still hypothetical and highly experimental.” And also “Whether embryonic stem cells will provide advantages over stem cells derived from cord blood or adult bone marrow hematopoietic stem cells remains to be determined.” There are no current clinical treatments based on embryonic stem cells, and there are in fact only few and modest published successes using animal models of disease. Those who work with embryonic stem cells even have difficulty obtaining pure cultures of specific cell types in the laboratory dish. For example, an Israeli group reported in 2001 that they had obtained insulin-secreting cells from human embryonic stem cells. While this report was seized on by the press as a potential treatment for diabetes, what was not reported, and what was revealed by the scientific paper, was that only 1% of the cells in the culture dish supposedly made insulin. The remaining 99% of the cells were a mixture of other cell types, including nerve, muscle, a few beating heart cells, and also cells which continued to proliferate. In fact, those growing cells point out another problem with embryonic stem cells—the potential for tumor formation. Embryonic stem cells have a distinct tendency to run out of control. Embryonic stem cells are actually difficult to establish and maintain in culture. James Thompson, who originated the first human embryonic stem cells in 1998, required 36 human embryos to finally obtain just 5 stem cell lines. Each stem cell line derives from one embryo. The Jones Institute in Virginia, in the summer of 2001, used 110 human embryos to derive 3 stem cell lines. And in the spring of 2004, a Harvard group used 342 human embryos to obtain 17 stem cell lines. In addition, embryonic stem cells face a significant risk of immune rejection. Tissue formed from embryonic stem cells will thus be rejected like most organ transplants without a precise tissue match. Indeed, a group from the Whitehead Institute reported that embryonic stem cells are actually genomically unstable, meaning that the expression of their genes is unstable: “The epigenetic state of the embryonic stem cell genome was found to be extremely unstable.” This might in fact explain why there is such difficulty in obtaining pure cultures and why they tend to form tumors. This may also explain the problems in achieving true functional differentiation of embryonic stem cells. This has been particularly troubling with regards to diabetes. While some reports have suggested that a fraction of embryonic stem cells could be stimulated to produce insulin, those reports were called into question by a Harvard study that indicated the embryonic stem cells were not making insulin themselves, but were imbibing it from the culture medium in which they were grown and then releasing it. Another recent study found that supposedly differentiated insulin-expressing embryonic stem cells were not actually true beta cells, and when injected into animals caused tumors. Human embryonic stem cells (even new lines) have been found to accumulate chromosomal abnormalities in culture as well. , It is illustrative to examine some quotes from proponents of embryonic stem cell research. In a review paper co-authored by James Thompson, the following statements are noteworthy: “Rarely have specific growth factors or culture conditions led to establishment of cultures containing a single cell type.” “Furthermore, there is significant culture-to-culture variability in the development of a particular phenotype under identical growth factor conditions.” “[T]he possibility arises that transplantation of differentiated human ES cell derivatives into human recipients may result in the formation of ES cell-derived tumors.” “[T]he poor availability of human oocytes, the low efficiency of the nuclear transfer procedure, and the long population-doubling time of human ES cells make it difficult to envision this [generation of human embryos by nuclear reprogramming] becoming a routine clinical procedure…” Other researchers have noted similar problems with embryonic stem cells: “The work presented here shows that none of the eight growth factors tested directs a completely uniform and singular differentiation of cells.” “Transplanted ES cells spontaneously differentiate into any of a variety of ectodermal, endodermal and mesodermal cell types—sometimes into a disorganized mass of neurons, cartilage and muscle; sometimes into teratomas containing an eye, hair or even teeth.” A commentary in the journal Science included the following: “[M]urine ES cells have a disturbing ability to form tumors, and researchers aren’t yet sure how to counteract that. And so far reports of pure cell populations derived from either human or mouse ES cells are few and far between--fewer than those from adult cells.” “Bone marrow stem cells can probably form any cell type,” says Harvard’s [Douglas] Melton. And a commentary in the New England Journal of Medicine noted the significant problems still facing potential utility of embryonic stem cells: “There are still many hurdles to clear before embryonic stem cells can be used therapeutically. For example, because undifferentiated embryonic stem cells can form tumors after transplantation in histocompatible animals, it is important to determine an appropriate state of differentiation before transplantation. Differentiation protocols for many cell types have yet to be established. Targeting the differentiated cells to the appropriate organ and the appropriate part of the organ is also a challenge.” Furthermore, the theory that cloning (SCNT) will produce matching tissues for transplant that will not be rejected has already been shown incorrect. When tested in mice, the ES cells from the cloned mouse embryo were rejected by the genetically-identical host: “Jaenisch addressed the possibility that ES clones derived by nuclear transfer technique could be used to correct genetic defects… However, the donor cells, although derived from the animals with the same genetic background, are rejected by the hosts.” As noted above, Dr. James Thomson has stated that cloning is unlikely to be clinically significant. Other leaders in the embryonic stem cell field have also published similar views, including Australia’s Alan Trounson: “However, it is unlikely that large numbers of mature human oocytes would be available for the production of ES cells, particularly if hundreds are required to produce each ES line… In addition, epigenetic remnants of the somatic cell used as the nuclear donor can cause major functional problems in development, which must remain a concern for ES cells derived by nuclear transfer. …it would appear unlikely that these strategies will be used extensively for producing ES cells compatible for transplantation.” The evidence from animal studies indicates that it will indeed require a tremendous number of human oocytes to produce even one ES line from cloned embryos. Dr. Peter Mombaerts, who was one of the first mouse cloners, estimates that it will require a minimum of 100 eggs. The reported first cloning of a human embryo in South Korea this year actually required 242 eggs to obtain just one ES cell line. There are in truth few actual positive published scientific reports regarding the claims put forth for embryonic stem cells, and a significant number of negative characteristics. At present embryonic stem cells have shown modest success in repairing spinal cord damage and Parkinson’s disease, though the latter experiments showed significant tumor formation in the animals. The theoretical potential of embryonic stem cells to treat diseases, and the theoretical ability to control their differentiation without tumor formation, is wishful thinking. The relative lack of success of embryonic stem cells should be compared with the real success of adult stem cells. A wealth of scientific papers published over the last few years document that adult stem cells are a much more promising source of stem cells for regenerative medicine. Adult stem cells actually do show pluripotent capacity in generation of tissues, meaning that they can generate most, if not all, tissues of the body. In a paper published in May 2001, the researchers found that one adult bone marrow stem cell could regenerate not only marrow and blood, but also form liver, lung, digestive tract, skin, heart, muscle. Other researchers have found pluripotent ability of adult stem cells various sources including from bone marrow, , peripheral blood, inner ear, and umbilical cord blood. The chart attached as Appendix A shows examples (not all-inclusive) of tissues from which adult stem cells have been isolated, as well as some of the derivatives from those stem cells. Bone marrow stem cells seem particularly “plastic”, potentially with the ability to form all adult tissues. Even liposuctioned fat has been found to contain stem cells which can be transformed into other tissues. In point of fact, any time someone has looked in a tissue for stem cells, they have found them. Many published references also show that adult stem cells can multiply in culture for extensive periods of time, retaining their ability to differentiate, and providing sufficient numbers of cells for clinical treatments. More importantly, adult stem cells have been shown to be effective in treating animal models of disease, including such diseases as diabetes, stroke, spinal cord injury, Parkinson’s disease, and retinal degeneration. Moreover, adult stem cells are already being used clinically for many diseases. These include as reparative treatments with various cancers, autoimmune diseases such as multiple sclerosis, lupus, and arthritis, anemias including sickle cell anemia, and immunodeficiencies. Adult stem cells are also being used to treat patients by formation of cartilage, growing new corneas to restore sight to blind patients, treatments for stroke, and several groups are using adult stem cells with patients to repair damage after heart attacks. Early clinical trials have shown initial success in patient treatments for Parkinson’s disease and spinal cord injury. An advantage of using adult stem cells is that in most cases the patient’s own stem cells can be used for the treatment, circumventing the problems of immune rejection, and without tumor formation. The mechanism for these amazing regenerative treatments is still unclear. Adult stem cells in some cases appear capable of interconversion between different tissue types, known as transdifferentiation. In some tissues, adult stem cells appear to fuse with the host tissue and take on that tissue’s characteristics, facilitating regeneration. And in some studies, the adult stem cells do not directly contribute to the regenerating tissue, but instead appear to stimulate the endogenous cells of the tissue to begin repair. Whatever the mechanism, the adult cells are successful at regenerating damaged tissue. As Robert Lanza, a proponent of embryonic stem cells and cloning has noted, “there is ample scientific evidence that adult stem cells can be used to repair damaged heart or brain tissue… if it works, it works, regardless of the mechanism.” The citations given above for adult stem cells are only a sampling, including some more recent references. A representative list of diseases currently in patient clinical trials with adult stem cells is given as Appendix B. A more complete review of the recent adult stem cell literature is appended at the end, as a paper prepared for the President’s Council on Bioethics in 2003 (see: http://bioethics.gov/reports/stemcell/appendix_k.html). In summary, adult stem cells have been shown by the published evidence to be a more promising alternative for patient treatments, with a vast biomedical potential. Adult stem cells have proven success in the laboratory dish, in animal models of disease, and in current clinical treatments. Adult stem cells also avoid problems with tumor formation, transplant rejection, and provide realistic excitement for patient treatments. Mr. Chairman, Distinguished Members, thank you once again for allowing me to present testimony on this issue. Appendix A Post-Natal (non-embryonic) Stem Cells and their Known or Possible Derivatives (not an all-inclusive list) (From the peer-reviewed scientific literature; for placenta by company press releases) Appendix B CURRENT CLINICAL APPLICATIONS OF ADULT STEM CELLS (not a complete listing) ADULT STEM CELLS--HEMATOPOIETIC REPLACEMENT CANCERS BRAIN TUMORS—medulloblastoma and glioma Dunkel, IJ; “High-dose chemotherapy with autologous stem cell rescue for malignant brain tumors”; Cancer Invest. 18, 492-493; 2000. Abrey, LE et al.; “High dose chemotherapy with autologous stem cell rescue in adults with malignant primary brain tumors”; J. Neurooncol. 44, 147-153; Sept., 1999 Finlay, JL; “The role of high-dose chemotherapy and stem cell rescue in the treatment of malignant brain tumors: a reappraisal”; Pediatr. Transplant 3 Suppl. 1, 87-95; 1999 RETINOBLASTOMA Hertzberg H et al.; “Recurrent disseminated retinoblastoma in a 7-year-old girl treated successfully by high-dose chemotherapy and CD34-selected autologous peripheral blood stem cell transplantation”; Bone Marrow Transplant 27(6), 653-655; March 2001 Dunkel IJ et al.; “Successful treatment of metastatic retinoblastoma”; Cancer 89, 2117-2121; Nov 15 2000 OVARIAN CANCER Stiff PJ et al.; “High-dose chemotherapy and autologous stem-cell transplantation for ovarian cancer: An autologous blood and marrow transplant registry report”; Ann. Intern. Med. 133, 504-515; Oct. 3, 2000 Schilder, RJ and Shea, TC; “Multiple cycles of high-dose chemotherapy for ovarian cancer”; Semin. Oncol. 25, 349-355; June 1998 MERKEL CELL CARCINOMA Waldmann V et al.; “Transient complete remission of metastasized merkel cell carcinoma by high-dose polychemotherapy and autologous peripheral blood stem cell transplantation”; Br. J. Dermatol. 143, 837-839; Oct 2000 TESTICULAR CANCER Bhatia S et al.; “High-dose chemotherapy as initial salvage chemotherapy in patients with relapsed testicular cancer”; J. Clin. Oncol. 18, 3346-3351; Oct. 19, 2000 Hanazawa, K et al.; “Collection of peripheral blood stem cells with granulocyte-colony-stimulating factor alone in testicular cancer patients”; Int. J. Urol. 7, 77-82; March 2000. LYMPHOMA Tabata M et al.; “Peripheral blood stem cell transplantation in patients over 65 years old with malignant lymphoma--possibility of early completion of chemotherapy and improvement of performance status”; Intern Med 40, 471-474; June 2001 Josting, A; “Treatment of Primary Progressive Hodgkin’s and Aggressive Non-Hodgkin’s Lymphoma: Is There a Chance for Cure?”; J Clin Oncol 18, 332-339; 2000 Koizumi M et al.; “Successful treatment of intravascular malignant lymphomatosis with high-dose chemotherapy and autologous peripheral blood stem cell transplantation”; Bone Marrow Transplant 27, 1101-1103; May 2001 ACUTE LYMPHOBLASTIC LEUKEMIA Ohnuma K et al.; “Cord blood transplantation from HLA-mismatched unrelated donors as a treatment for children with haematological malignancies”; Br J Haematol 112(4), 981-987; March 2001 Marco F et al.; “High Survival Rate in Infant Acute Leukemia Treated With Early High-Dose Chemotherapy and Stem-Cell Support”; J Clin Oncol 18, 3256-3261; Sept. 15 2000 ACUTE MYELOGENOUS LEUKEMIA Ohnuma K et al.; “Cord blood transplantation from HLA-mismatched unrelated donors as a treatment for children with haematological malignancies”; Br J Haematol 112(4), 981-987; March 2001 Gorin NC et al.; “Feasibility and recent improvement of autologous stem cell transplantation for acute myelocytic leukaemia in patients over 60 years of age: importance of the source of stem cells”; Br. J. Haematol. 110, 887-893; Sept 2000 Bruserud O et al.; “New strategies in the treatment of acute myelogenous leukemia: mobilization and transplantation of autologous peripheral blood stem cells in adult patients”; Stem Cells 18, 343-351; 2000 CHRONIC MYELOGENOUS LEUKEMIA Ohnuma K et al.; “Cord blood transplantation from HLA-mismatched unrelated donors as a treatment for children with haematological malignancies”; Br J Haematol 112(4), 981-987; March 2001 JUVENILE MYELOMONOCYTIC LEUKEMIA Ohnuma K et al.; “Cord blood transplantation from HLA-mismatched unrelated donors as a treatment for children with haematological malignancies”; Br J Haematol 112(4), 981-987; March 2001 ANGIOIMMUNOBLASTIC LYMPHADENOPATHY with DYSPROTEINEMIA Lindahl J et al.; “High-dose chemotherapy and APSCT as a potential cure for relapsing hemolysing AILD”; Leuk Res 25(3), 267-270; March 2001 MULTIPLE MYELOMA Laughlin MJ et al.; “Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors”, New England Journal of Medicine 344, 1815-1822; June 14, 2001 Vesole, DH et al.; “High-Dose Melphalan With Autotransplantation for Refractory Multiple Myeloma: Results of a Southwest Oncology Group Phase II Trial”; J Clin Oncol 17, 2173-2179; July 1999. MYELODYSPLASIA Ohnuma K et al.; “Cord blood transplantation from HLA-mismatched unrelated donors as a treatment for children with haematological malignancies”; Br J Haematol 112(4), 981-987; March 2001 Bensinger WI et al.; “Transplantation of bone marrow as compared with peripheral-blood cells from HLA-identical relatives in patients with hematologic cancers”; New England Journal of Medicine 344, 175-181; Jan 18 2001 BREAST CANCER Damon LE et al.; “High-dose chemotherapy and hematopoietic stem cell rescue for breast cancer: experience in California”; Biol. Blood Marrow Transplant 6, 496-505; 2000 Paquette, RL et al., “Ex vivo expanded unselected peripheral blood: progenitor cells reduce posttransplantation neutropenia, thrombocytopenia, and anemia in patients with breast cancer”, Blood 96, 2385-2390; October, 2000. Stiff P et al.; “Autologous transplantation of ex vivo expanded bone marrow cells grown from small aliquots after high-dose chemotherapy for breast cancer”; Blood 95, 2169-2174; March 15, 2000 Koc, ON et al.; “Rapid Hematopoietic Recovery After Coinfusion of Autologous-Blood Stem Cells and Culture-Expanded Marrow Mesenchymal Stem Cells in Advanced Breast Cancer Patients Receiving High-Dose Chemotherapy”; J Clin Oncol 18, 307-316; January 2000 NEUROBLASTOMA Kawa, K et al.; “Long-Term Survivors of Advanced Neuroblastoma With MYCN Amplification: A Report of 19 Patients Surviving Disease-Free for More Than 66 Months”; J Clin Oncol 17:3216-3220; October 1999 NON-HODGKIN’S LYMPHOMA Tabata M et al.; “Peripheral blood stem cell transplantation in patients over 65 years old with malignant lymphoma--possibility of early completion of chemotherapy and improvement of performance status”; Intern Med 40, 471-474; June 2001 Josting, A; “Treatment of Primary Progressive Hodgkin’s and Aggressive Non-Hodgkin’s Lymphoma: Is There a Chance for Cure?”; J Clin Oncol 18, 332-339; 2000 Kirita T et al.; “Primary non-Hodgkin’s lymphoma of the mandible treated with radiotherapy, chemotherapy, and autologous peripheral blood stem cell transplantation”; Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 90, 450-455; Oct. 2000 Yao M et al.; “Ex vivo expansion of CD34-positive peripheral blood progenitor cells from patients with non-Hodgkin’s lymphoma: no evidence of concomitant expansion of contaminating bcl2/JH-positive lymphoma cells”; Bone Marrow Transplant 26, 497-503; Sept. 2000 HODGKIN’S LYMPHOMA Josting, A; “Treatment of Primary Progressive Hodgkin’s and Aggressive Non-Hodgkin’s Lymphoma: Is There a Chance for Cure?”; J Clin Oncol 18, 332-339; 2000 RENAL CELL CARCINOMA Childs R et al., “Regression of Metastatic Renal-Cell Carcinoma after Nonmyeloablative Allogeneic Peripheral-Blood Stem-Cell Transplantation”, New England Journal of Medicine 343, 750-758; Sept. 14, 2000 Childs, RW; “Successful Treatment of Metastatic Renal Cell Carcinoma With a Nonmyeloablative Allogeneic Peripheral-Blood Progenitor-Cell Transplant: Evidence for a Graft-Versus-Tumor Effect:; J Clin Oncol 17, 2044-2049; July 1999 VARIOUS SOLID TUMORS Nieboer P et al.; “Long-term haematological recovery following high-dose chemotherapy with autologous bone marrow transplantation or peripheral stem cell transplantation in patients with solid tumours”; Bone Marrow Transplant 27, 959-966; May 2001 Lafay-Cousin L et al.; “High-dose thiotepa and hematopoietic stem cell transplantation in pediatric malignant mesenchymal tumors: a phase II study”; Bone Marrow Transplant 26, 627-632; Sept. 2000 Michon, J and Schleiermacher, G. “Autologous haematopoietic stem cell transplantation for paediatric solid tumors”, Baillieres Best Practice Research in Clinical Haematology 12, 247-259, March-June, 1999. Schilder, RJ et al.; “Phase I trial of multiple cycles of high-dose chemotherapy supported by autologous peripheral-blood stem cells”; J. Clin. Oncol. 17, 2198-2207; July 1999 SOFT TISSUE SARCOMA Blay JY et al.; “High-dose chemotherapy with autologous hematopoietic stem-cell transplantation for advanced soft tissue sarcoma in adults”; J. Clin. Oncol. 18, 3643-3650; Nov 1 2000 ADULT STEM CELLS—IMMUNE SYSTEM REPLACEMENT AUTOIMMUNE DISEASES SCLEROMYXEDEMA A.M. Feasel et al., "Complete remission of scleromyxedema following autologous stem cell transplantation," Archives of Dermatology 137, 1071-1072; Aug. 2001. MULTIPLE SCLEROSIS Mancardi GL et al.; “Autologous hematopoietic stem cell transplantation suppresses Gd-enhanced MRI activity in MS”; Neurology 57, 62-68; July 10, 2001 Rabusin M et al.; “Immunoablation followed by autologous hematopoietic stem cell infusion for the treatment of severe autoimmune disease”; Haematologica 85(11 Suppl), 81-85; Nov. 2000 Burt, RK and Traynor, AE; “Hematopoietic Stem Cell Transplantation: A New Therapy for Autoimmune Disease”; Stem Cells17, 366-372; 1999 Burt RK et al.; “Hematopoietic stem cell transplantation of multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus”; Cancer Treat. Res. 101, 157-184; 1999 CROHN’S DISEASE Burt RK et al., “High-dose immune suppression and autologous hematopoietic stem cell transplantation in refractory Crohn disease”, Blood 101, 2064-2066, March 2003 Rabusin M et al.; “Immunoablation followed by autologous hematopoietic stem cell infusion for the treatment of severe autoimmune disease”; Haematologica 85(11 Suppl), 81-85; Nov. 2000 Hawkey CJ et al.; “Stem cell transplantation for inflammatory bowel disease: practical and ethical issues”; Gut 46, 869-872; June 2000 RHEUMATOID ARTHRITIS Burt RK et al., “Induction of remission of severe and refractory rheumatoid arthritis by allogeneic mixed chimerism”, Arthritis & Rheumatism 50, 2466-2470, August 2004 Verburg RJ et al.; “High-dose chemotherapy and autologous hematopoietic stem cell transplantation in patients with rheumatoid arthritis: results of an open study to assess feasibility, safety, and efficacy”; Arthritis Rheum 44(4), 754-760; April 2001 Rabusin M et al.; “Immunoablation followed by autologous hematopoietic stem cell infusion for the treatment of severe autoimmune disease”; Haematologica 85(11 Suppl), 81-85; Nov. 2000 Burt, RK and Traynor, AE; “Hematopoietic Stem Cell Transplantation: A New Therapy for Autoimmune Disease”; Stem Cells17, 366-372; 1999 Burt RK et al.; “Hematopoietic stem cell transplantation of multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus”; Cancer Treat. Res. 101, 157-184; 1999 Burt, RK et al., “Autologous hematopoietic stem cell transplantation in refractory rheumatoid arthritis: sustained response in two of four patients”, Arthritis & Rheumatology 42, 2281-2285, November, 1999. JUVENILE ARTHRITIS Rabusin M et al.; “Immunoablation followed by autologous hematopoietic stem cell infusion for the treatment of severe autoimmune disease”; Haematologica 85(11 Suppl), 81-85; Nov. 2000 Burt, RK and Traynor, AE; “Hematopoietic Stem Cell Transplantation: A New Therapy for Autoimmune Disease”; Stem Cells17, 366-372; 1999 SYSTEMIC LUPUS Wulffraat NM et al.; “Prolonged remission without treatment after autologous stem cell transplantation for refractory childhood systemic lupus erythematosus”; Arthritis Rheum 44(3), 728-731; March 2001 Rosen O et al.; “Autologous stem-cell transplantation in refractory autoimmune diseases after in vivo immunoablation and ex vivo depletion of mononuclear cells”; Arthritis res. 2, 327-336; 2000 Traynor AE et al.; “Treatment of severe systemic lupus erythematosus with high-dose chemotherapy and haemopoietic stem-cell transplantation: a phase I study”; Lancet 356, 701-707; August 26, 2000 Burt, RK and Traynor, AE; “Hematopoietic Stem Cell Transplantation: A New Therapy for Autoimmune Disease”; Stem Cells17, 366-372; 1999 Burt RK et al.; “Hematopoietic stem cell transplantation of multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus”; Cancer Treat. Res. 101, 157-184; 1999 Traynor A and Burt RK; “Haematopoietic stem cell transplantation for active systemic lupus erythematosus”; Rheumatology 38, 767-772; August 1999 Martini A et al.; “Marked and sustained improvement 2 years after autologous stem cell transplant in a girl with system sclerosis”; Rheumatology 38, 773; August 1999 POLYCHONDRITIS Rosen O et al.; “Autologous stem-cell transplantation in refractory autoimmune diseases after in vivo immunoablation and ex vivo depletion of mononuclear cells”; Arthritis res. 2, 327-336; 2000 SYSTEMIC VASCULITIS Rabusin M et al.; “Immunoablation followed by autologous hematopoietic stem cell infusion for the treatment of severe autoimmune disease”; Haematologica 85(11 Suppl), 81-85; Nov. 2000 SJOGREN’S SYNDROME Rabusin M et al.; “Immunoablation followed by autologous hematopoietic stem cell infusion for the treatment of severe autoimmune disease”; Haematologica 85(11 Suppl), 81-85; Nov. 2000 BEHCET’S DISEASE Rabusin M et al.; “Immunoablation followed by autologous hematopoietic stem cell infusion for the treatment of severe autoimmune disease”; Haematologica 85(11 Suppl), 81-85; Nov. 2000 MYASTHENIA Rabusin M et al.; “Immunoablation followed by autologous hematopoietic stem cell infusion for the treatment of severe autoimmune disease”; Haematologica 85(11 Suppl), 81-85; Nov. 2000 RED CELL APLASIA Rabusin M et al.; “Immunoablation followed by autologous hematopoietic stem cell infusion for the treatment of severe autoimmune disease”; Haematologica 85(11 Suppl), 81-85; Nov. 2000 AUTOIMMUNE CYTOPENIA Rabusin M et al.; “Immunoablation followed by autologous hematopoietic stem cell infusion for the treatment of severe autoimmune disease”; Haematologica 85(11 Suppl), 81-85; Nov. 2000 Papadaki HA et al.; “Assessment of bone marrow stem cell reserve and function and stromal cell function in patients with autoimmune cytopenias”; Blood 96, 3272-3275; Nov 1 2000 IMMUNODEFICIENCIES Banked unrelated umbilical cord blood was used to reconstitute the immune system in 2 brothers with X-linked lymphoproliferative syndrome and 1 boy with X-linked hyperimmunoglobulin-M syndrome. Two years after transplantation, all 3 patients have normal immune systems. These reports support the wider use of banked partially matched cord blood for transplantation in primary immunodeficiencies. Reference: Ziegner UH et al.; “Unrelated umbilical cord stem cell transplantation for X-linked immunodeficiencies”; J Pediatr 138(4), 570-573; April 2001 Eight children with severe immunodeficiencies treated by adult bone marrow stem cell transplants. Six of 8 showed relatively normal immune systems after 1 year. Reference Amrolia, P. et al., “Nonmyeloablative stem cell transplantation for congenital immunodeficiencies”, Blood 96, 1239-1246, Aug. 15, 2000. SEVERE COMBINED IMMUNODEFICIENCY SYNDROME-X1 (ASC gene therapy) Cavazzana-Calvo M et al.; “Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease”; Science 288, 669-672; April 28, 2000 ANEMIAS SICKLE CELL ANEMIA Gore L. et al.; “Successful cord blood transplantation for sickle cell anemia from a sibling who is human leukocyte antigen-identical: implications for comprehensive care”, J Pediatr Hematol Oncol 22(5):437-440; Sep-Oct 2000 Steen RG et al.; “Improved cerebrovascular patency following therapy in patients with sickle cell disease: initial results in 4 patients who received HLA-identical hematopoietic stem cell allografts”; Ann Neurol 49(2), 222-229; Feb. 2001 Wethers DL; “Sickle cell disease in childhood: Part II. Diagnosis and treatment of major complications and recent advances in treatment”; Am. Fam. Physician 62, 1309-1314; Sept. 15, 2000 SIDEROBLASTIC ANEMIA Ayas M et al.; “Congenital sideroblastic anaemia successfully treated using allogeneic stem cell transplantation”; Br J Haematol 113, 938-939; June 2001 Gonzalez MI et al.; “Allogeneic peripheral stem cell transplantation in a case of hereditary sideroblastic anaemia”; British Journal of Haematology 109, 658-660; 2000 WALDENSTROM’S MACROGLOBULINEMIA Anagnostopoulos A et al.; “High-dose chemotherapy followed by stem cell transplantation in patients with resistant Waldenstrom's macroglobulinemia”; Bone Marrow Transplant 27, 1027-1029; May 2001 APLASTIC ANEMIA Gurman G et al.; “Allogeneic peripheral blood stem cell transplantation for severe aplastic anemia”; Ther Apher 5(1), 54-57; Feb. 2001 Kook H et al.; “Rubella-associated aplastic anemia treated by syngeneic stem cell transplantations”; Am. J. Hematol. 64, 303-305; August 2000 AMEGAKARYOCYTIC THROMBOCYTOPENIA Yesilipek et al.; “Peripheral stem cell transplantation in a child with amegakaryocytic thrombocytopenia”; Bone Marrow Transplant 26, 571-572; Sept. 2000 CHRONIC EPSTEIN-BARR INFECTION Fujii N et al.; “Allogeneic peripheral blood stem cell transplantation for the treatment of chronic active epstein-barr virus infection”; Bone Marrow Transplant 26, 805-808; Oct. 2000 Okamura T et al.; “Blood stem-cell transplantation for chronic active Epstein-Barr virus with lymphoproliferation”; Lancet 356, 223-224; July 2000 FANCONI’S ANEMIA Kohli-Kumar M et al., “Haemopoietic stem/progenitor cell transplant in Fanconi anaemia using HLA-matched sibling umbilical cord blood cells”, British Journal of Haematology 85, 419-422, October 1993 DIAMOND BLACKFAN ANEMIA Ostronoff M et al., “Successful nonmyeloablative bone marrow transplantation in a corticosteroid-resistant infant with Diamond-Blackfan anemia”, Bone Marrow Transplant. 34, 371-372, August 2004 THALASSEMIA Tan PH et al., “Unrelated peripheral blood and cord blood hematopoietic stem cell transplants for thalassemia major”, Am J Hematol 75, 209-212, April 2004 STROKE Meltzer CC et al.; “Serial [18F]Fluorodeoxyglucose Positron Emission Tomography after Human Neuronal Implantation for Stroke”; Neurosurgery 49, 586-592; 2001. Kondziolka D et al.; “Transplantation of cultured human neuronal cells for patients with stroke”; Neurology 55, 565-569; August 2000 Cartilage and Bone Diseases OSTEOGENESIS IMPERFECTA Horwitz EM et al., “Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone”, Proceedings of the National Academy of Sciences USA 99, 8932-8937; 25 June 2002. Horwitz EM et al., “Clinical responses to bone marrow transplantation in children with severe osteogenesis imperfecta”, Blood 97, 1227-1231; 1 March 2001. Horwitz, EM et al.; “Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta”; Nat. Med. 5, 309-313; March 1999. SANDHOFF DISEASE CORNEAL REGENERATION Anderson DF et al.; “Amniotic Membrane Transplantation After the Primary Surgical Management of Band Keratopathy”; Cornea 20(4), 354-361; May 2001 Anderson DF et al.; “Amniotic membrane transplantation for partial limbal stem cell deficiency”; Br J Ophthalmol 85(5), 567-575; May 2001 Henderson TR et al.; “The long term outcome of limbal allografts: the search for surviving cells”; Br J Ophthalmol 85(5), 604-609; May 2001 Daya SM, Ilari FA; “Living related conjuctival limbal allograft for the treatment of stem cell deficiency”; Opthalmology 180, 126-133; January 2001 Schwab IR et al.; “Successful transplantation of bioengineered tissue replacements in patients with ocular surface disease”; Cornea 19, 421-426; July 2000. Tsai et al.; “Reconstruction of damaged corneas by transplantation of autologous limbal epithelial cells.”; New England Journal of Medicine 343, 86-93, 2000. Tsubota K et al.; “Treatment of severe ocular-surface disorders with corneal epithelial stem-cell transplantation”; New England Journal of Medicine 340, 1697-1703; June 3, 1999 Ocular corneal regeneration HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS Matthes-Martin S et al.; “Successful stem cell transplantation following orthotopic liver transplantation from the same haploidentical family donor in a girl with hemophagocytic lymphohistiocytosis”; Blood 96, 3997-3999; Dec 1, 2000 PRIMARY AMYLOIDOSIS Sezer O et al.; “Novel approaches to the treatment of primary amyloidosis”; Exper Opin. Investig. Drugs 9, 2343-2350; Oct 2000 LIMB GANGRENE Tateishi-Yuyama E et al.; “Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial”; Lancet 360, 427-435; 10 August 2002. SURFACE WOUND HEALING Badiavas EV, “Participation of Bone Marrow Derived Cells in Cutaneous Wound Healing”, Journal Of Cellular Physiology 196, 245-250; 2003. HEART DAMAGE Wollert KC et al., “Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial”, Lancet 364, 141-148, 10 July 2004 Britten MB et al., “Infarct remodeling after intracoronary progenitor cell treatment in patients with acute myocardial infarction”; Circulation 108, 2212-2218; Nov 2003 Perin EC et al.; “Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure”; Circulation 107, r75-r83; published online May 2003 Stamm C et al.; “Autologous bone-marrow stem-cell transplantation for myocardial regeneration”; The Lancet 361, 45-46; 4 January 2003 Tse H-F et al.; “Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation”; The Lancet 361, 47-49; 4 January 2003 Strauer BE et al.; “Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans”; Circulation 106, 1913-1918; 8 October 2002 Strauer BE et al.; “Myocardial regeneration after intracoronary transplantation of human autologous stem cells following acute myocardial infarction”; Dtsch Med Wochenschr 126, 932-938; Aug 24, 2001 Menasché P et al. “Myoblast transplantation for heart failure.” Lancet 357, 279-280; Jan 27, 2001 Menasché P et al. [“Autologous skeletal myoblast transplantation for cardiac insufficiency. First clinical case.”] [article in French] Arch Mal Coeur Vaiss 94(3), 180-182; March 2001 PARKINSON’S DISEASE Lévesque M and Neuman T, “Autologous transplantation of adult human neural stem cells and differentiated dopaminergic neurons for Parkinson disease: 1-year postoperative clinical and functional metabolic result”, American Association of Neurological Surgeons annual meeting, Abstract #702; 8 April 2002 Gill SS et al.; “Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease”; Nature Medicine 9, 589-595; May 2003 (published online 31 March 2003) See also July 14, 2004 Senate testimony by Dr. Michel Lévesque: http://commerce.senate.gov/hearings/testimony.cfm?id=1268&wit_id=3670 and Mr. Dennis Turner: http://commerce.senate.gov/hearings/testimony.cfm?id=1268&wit_id=3676 SPINAL CORD INJURY See July 14, 2004 Senate testimony by Dr. Jean Peduzzi-Nelson: http://commerce.senate.gov/hearings/testimony.cfm?id=1268&wit_id=3671 and a more extensive testimony at: http://www.stemcellresearch.org/testimony/peduzzi-nelson.htm and Ms. Laura Dominguez: http://commerce.senate.gov/hearings/testimony.cfm?id=1268&wit_id=3673 and Ms. Susan Fajt: http://commerce.senate.gov/hearings/testimony.cfm?id=1268&wit_id=3674 For appended paper, see http://bioethics.gov/reports/stemcell/appendix_k.html

• Dr. Marc Hedrick
  Read statement

  Witness Panel 2

  Dr. Marc Hedrick

  Mr. Chairman, Distinguished Members of Committee, I would like to thank you for the opportunity to be here today. I have been fortunate to have been involved on the front lines of the stem cell issue for some time. As a surgeon at UCLA, I saw first hand the need for stem cell treatments in my patients. As a researcher, I received NIH funding to study adult stem cells at our program at UCLA. And now I serve as President of MacroPore Biosurgery, a public company from San Diego, California. Our company is dedicated to developing adult stem cell therapies to help as many people as we can. Based on this experience, I feel I can say to you in the strongest possible terms, we truly are on the edge of a new frontier in medicine. Over the past two years, our company, has made a strategic decision to take a leadership role in developing adult stem cell therapies. This decision was based both on our excitement for the technology and our vision for what it could ultimately do for patients. If I may, permit to quote from the NIH website, “…given the enormous promise of stem cells to the development of new therapies for the most devastating diseases, when a readily available source of stem cells is identified, it is not too unrealistic to say that this research will revolutionize the practice of medicine and improve the quality and length of life.” And that is absolutely is our goal. We agree with the NIH that cell availability has been a significant challenge not only for the clinical, but for the commercial application of stem cells. Stem cells have been thought to be rare, difficult to obtain, often requiring long periods of cell culture or multiplication. But today, we have found a potential solution to the significant challenge of cell availability. We believe the solution is the use of fat or adipose tissue, as a source of stem cells. This is a low cost, high volume alternative to other stem cell sources. This technology enables us to rethink how patients may be treated using their own stem cells. This is an important breakthrough for adult stem cell therapies. From adipose, we can obtain at least two of the key types of adult stem cells that can potentially treat many diseases such as: · heart disease; · stroke; · injured bones and joints; · degenerative spinal disease; and · vascular diseases. The first adult stem cells were identified about 40 years ago in bone marrow. Since then, bone marrow transplants have been used to treat many diseases, specifically blood diseases and cancer. And until recently, bone marrow was thought to be the only significant clinical reservoir of adult stem cells. But even this source yields a relatively limited number of cells. So how does adipose measure up as a stem cell source? Well, one cup of adipose tissue can yield approximately 1 million stem cells. This is about 100x more stem cells found in the same amount of bone marrow. Let me use myself as an example: I am six feet, one inch tall my weight is 180 pounds; and fifteen percent of my body weight is adipose. So I have 27 pounds of fat on me, which represents over 6 billion adult stem cells. What does this mean? It means opportunities - opportunities for your own body to potentially heal itself with its own cells, not within days or weeks but within an hour. What we are talking about here is ‘real-time’ stem cell therapy. This real-time approach is not just conceptual. This week, at a cardiology meeting in Washington, D.C., our Company along with our collaborators at UCLA and Cedars Sinai, reported that adipose derived stem cells are safe and improve heart function after heart attacks. We used pigs in this study because they are predictive of future success in the treatment of human heart attacks. Heart disease is becoming the most promising emerging area for the use of stem cell therapy. In 15 years, cardiovascular disease will be the principle cause of death worldwide. Over 1 million Americans each year have a heart attack and another 6 million have significant heart failure. Sadly though, that means that one out of every three people in this room will die of cardiovascular disease. It’s a staggering thought. MacroPore is addressing this clinical need by developing a unique system that enables doctors to treat patients with their own stem cells from adipose tissue. If successful, this system will fundamentally change the state of the art for heart attack treatment. It will enable us to move from supportive care- which is what we do now- to regenerative therapy. Both our research and that of others indicates that adult stem cells can do 3 important things for the ailing heart: · make new heart cells, · make new blood vessels, · and rescue dying heart muscle. While the science is complex; for the doctor and patient, the procedure represents a simple way to help heal the heart. Seven clinical studies, mostly clinician initiated, are now in progress around the world to study adult stem cells for cardiovascular disease. The early results are promising. For example, follow up data just presented from the joint Texas Heart Institute and Brazilian heart failure/stem cell human trial noted that four out of five patients being studied were no longer in need of a heart transplant after being treated with adult marrow stem cells. But despite all the clinical success of adult stem cells, misconceptions are still commonplace. For example, in a recent study of Americans who claim to be knowledgeable about stem cells, Sixty-eight percent thought that adult stem cells come from embryos. Other misconceptions are more subtle. Some think that adult stem cells are too rare, don’t multiply well enough, or are too limited in their potency to ever be useful. But all of these misconceptions are just that, they are not factually correct. The truth is that both bone marrow and adipose tissue are plentiful and clinically promising sources of adult stem cells. They grow well and have the ability to make and repair many tissue types throughout the body. We often make the mistake of referring to the promise of stem cells as if it’s a future event. In fact, this ‘promise’ has become a reality. The list of successful therapies using adult stem cell grows each year, as does the list of patients helped. While there is still a lot of work to be done, I would humbly remind you that, in many cases, the promise is already being realized.