6
Findings and Recommendations

Human reproductive cloning is currently the subject of much debate around the world, involving a variety of ethical, religious, societal, scientific, and medical issues. This report from the National Academies addresses only the scientific and medical aspects of human cloning. Consideration of the medical aspects has required the panel to examine issues of scientific conduct and human-subjects protection. But we have not attempted to address the issue of whether cloning, if it were found to be scientifically safe, would or would not be acceptable to individuals or society. Instead, the panel defers to others on the fundamental ethical, religious, and societal questions, and presents this report on the scientific and medical aspects to inform the broader debate. This report differs in this respect from the last major report on the topic in the United States, Cloning Human Beings, a 1997 report developed by the National Bioethics Advisory Commission (NBAC) [1].

Four of the questions in our statement of task remain for the panel to answer:

  • What scientific and medical criteria should be used to evaluate the safety of cloning a person?

  • What issues of responsible conduct of research are raised by the prospect of cloning a person?

  • What process should be used to evaluate future scientific and medical evidence regarding cloning a person?

  • Based on the current scientific and medical evidence, should there



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Scientific and Medical of Aspects: Human Reproductive Cloning 6 Findings and Recommendations Human reproductive cloning is currently the subject of much debate around the world, involving a variety of ethical, religious, societal, scientific, and medical issues. This report from the National Academies addresses only the scientific and medical aspects of human cloning. Consideration of the medical aspects has required the panel to examine issues of scientific conduct and human-subjects protection. But we have not attempted to address the issue of whether cloning, if it were found to be scientifically safe, would or would not be acceptable to individuals or society. Instead, the panel defers to others on the fundamental ethical, religious, and societal questions, and presents this report on the scientific and medical aspects to inform the broader debate. This report differs in this respect from the last major report on the topic in the United States, Cloning Human Beings, a 1997 report developed by the National Bioethics Advisory Commission (NBAC) [1]. Four of the questions in our statement of task remain for the panel to answer: What scientific and medical criteria should be used to evaluate the safety of cloning a person? What issues of responsible conduct of research are raised by the prospect of cloning a person? What process should be used to evaluate future scientific and medical evidence regarding cloning a person? Based on the current scientific and medical evidence, should there

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Scientific and Medical of Aspects: Human Reproductive Cloning be a moratorium on the cloning of a person? What are the implications of doing so? Of not doing so? If a moratorium is enacted, when should the issue be re-evaluated? The panel’s findings with respect to these questions are presented here and are followed by our recommendations based on them. THE FINDINGS THAT SUPPORT A BAN ON HUMAN REPRODUCTIVE CLONING It is a serious event when any group that has potential authority over research intercedes to ban it, and the reasons must therefore be compelling. We are convinced that the scientific and medical data concerning the likely danger to the implanted fetus or the eventual newborn if reproductive cloning of humans is attempted in the near future are very compelling. The panel has based its support for the proposed ban on human reproductive cloning on the following findings: Finding 1: The scientific and medical criteria used to evaluate the safety of reproductive cloning must be the potential morbidity and death of the woman carrying the clone as a fetus and of the newborn and the risk to women donating the eggs. Finding 2: Data on the reproductive cloning of animals through the use of nuclear transplantation technology demonstrate that only a small percentage of attempts are successful; that many of the clones die during gestation, even at late stages; that newborn clones are often abnormal or die; and that the procedures may carry serious risks for the mother. In addition, because of the large number of eggs needed for such experiments, many more women would be exposed to the risks inherent in egg donation for a single cloning attempt than for the reproduction of a child by the presently used in vitro fertilization (IVF) techniques. These medical and scientific findings lead us to conclude that the procedures are now unsafe for humans. Finding 3: At least three criteria would have to be fulfilled before the safety of human reproductive cloning could be established: The procedures for animal reproductive cloning would have to be improved to such an extent that the levels of observed abnormalities in cloned animals, including nonhuman primates, were no more than that seen with existing human assisted reproductive technology (ART) procedures. If that could not be achieved, researchers would have to demonstrate that humans are different from other

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Scientific and Medical of Aspects: Human Reproductive Cloning animals with regard to cloning-related defects. Reproducible data demonstrating that a successful reprogramming of the donor nucleus and proper imprinting can be achieved in animals would be essential, as would an understanding of the mechanisms responsible for such events. New methods would have to be developed to demonstrate that the human preimplantation embryos produced through the use of nuclear transplantation technology are normal with respect to imprinting and reprogramming. That would best be done by first establishing the normal state of reprogramming and imprinting in nonhuman primates and then documenting that the processes in preimplantation human embryos are substantially similar. Methods would have to be developed to monitor—effectively and comprehensively—preimplantation embryos and fetuses in the uterus for cloning-related defects, such as those outlined in Chapter 3; these include alterations in gene expression and imprinting. Finding 4: The issues of responsible conduct of research raised by the prospect of cloning a person are those of medical ethics—in particular, the protection of the participants (the egg donor, the host mother, and the child produced through cloning) in any human cloning research. Participants in any human cloning research efforts require full protection as human research participants, although it should be noted that, as with fetal surgery, this protection cannot be extended fully to the cloned fetus. Human reproductive cloning has not been performed before, and its introduction, if it ever occurred, would require systematic research. That research would likely entail full review by institutional review boards and other human-subjects protections, including informed consent of donors and recipients of all biological materials. Finding 5: If any attempts at human reproductive cloning were ever to occur, they would constitute research, not merely innovative therapy. Such research could then be subject to external technical and ethical review by review boards to ensure that the proposed experiments are both technically and ethically sound and that the rights and welfare of all research participants are protected. This institutional review process should be applied equally to both public- and private-sector research and be transparent to the public. Finding 6: Because medical and scientific findings indicate that cloning procedures are currently not safe for humans, cloning of a human through the use of nuclear transplantation technology is not now appropriate. The panel believes that no responsible scientists or physicians are

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Scientific and Medical of Aspects: Human Reproductive Cloning likely to undertake to clone a human. Nevertheless, no voluntary system that is established to restrict reproductive cloning is likely to be completely effective. Some organizations have already announced their intention to clone humans, and many of the reproductive technologies needed are widely accessible in private fertility clinics that are not subject to federal regulations. The panel therefore concludes that a legally enforceable ban that carries substantial penalties has a much greater potential than a voluntary system or moratorium to deter any attempt to clone a human using these techniques. Finding 7: If no ban is imposed, it is possible that some organizations will attempt the reproductive cloning of humans. Although such attempts would most likely fail, there is a high probability they would be associated with serious risks to any possible fetus or newly born child and may harm the woman carrying the developing fetus. Finding 8: There is concern that legislation or regulation that would ban reproductive human cloning would set a troubling precedent with respect to the restriction of innovative, experimental research and medical procedures. Modern scientific research proceeds rapidly, and its findings are unpredictable and often surprising. It is probable that at least every 5 years there will be significant new information regarding the issues of the safety and applicability of human cloning to medical practice. The above concern can be ameliorated by including in any legislation or regulation a requirement for an updated evaluation of the scientific, medical, and societal issues within 5 years. Such a requirement for periodic reviews would allow for extensive public debate regarding reproductive human cloning and the consideration of modifications to the legislation. Part of that evaluation would include a recommendation as to when the next such evaluation should be conducted. Finding 9: Two activities will be particularly important for an updated evaluation of human reproductive cloning: a thorough scientific and medical review to evaluate whether the procedures are likely to be safe and effective, and a broad national dialogue on the societal, religious, and ethical issues. As part of this process, any persons advocating the practice of human reproductive cloning would need to acknowledge the extent of the abnormalities seen in animal cloning experiments and to demonstrate that these problems—assuming that they still persist—are unlikely to occur in humans. Finding 10: Any future process designed to evaluate the scientific and medical evidence on cloning a person would likely need to involve

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Scientific and Medical of Aspects: Human Reproductive Cloning scientists, physicians, ethicists, and the public. A public debate could be facilitated by a committee that issues regular updates on the state of the science surrounding animal cloning and reaches out to involved constituencies in a systematic manner. Such a body could derive its powers by executive order, by executive action within the Department of Health and Human Services under the Public Health Service Act, or by legislation. Among many other issues, the debate should be structured to inform the public that clones are not precise replicas, but persons with identical genetic material. Finding 11: The science of cloning is an international one with research conducted throughout the world. Furthermore, the issue of human reproductive cloning is the subject of worldwide debate. A number of countries and international organizations have prepared reports and issued statements on the issue. Participation by the United States in such international debates about human reproductive cloning will be beneficial to any future process to evaluate the scientific and medical evidence on this issue. Finding 12: The limited regulation and monitoring of experimental ART procedures in the United States means that important data needed for assessing novel ART procedures are in some cases lacking, in other cases incomplete and hard to find. Because the panel was not charged to investigate ART regulation and did not solicit expert testimony thereon, we make no recommendations regarding oversight of, registration of, or required data collection from ART clinics. But we do believe that a request from Congress or the Executive Branch for a panel of experts to study the matter and report its findings and recommendations publicly would probably be useful. Having such information is likely to be beneficial to any process of evaluating future scientific and medical evidence regarding both reproductive cloning and new ART procedures. IMPLICATIONS OF THE PROPOSED BAN ON REPRODUCTIVE CLONING FOR NUCLEAR TRANSPLANTATION TO PRODUCE STEM CELLS As part of our panel’s charge, we were asked: “Based on the current scientific and medical evidence, should there be a moratorium on the cloning of a person? What are the implications of doing so? Of not doing so?” This raises the question of the implications of a ban on human reproductive cloning for the very different process of nuclear transplantation to produce stem cells. None of the findings summarized in the preceding section that sup-

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Scientific and Medical of Aspects: Human Reproductive Cloning port the panel’s conclusions regarding a ban on human reproductive cloning would support a ban on the use of the nuclear transplantation technology to produce stem cells. An independent recent report from the National Academies has emphasized that there is a great potential for studies on stem cells isolated through nuclear transplantation to increase the understanding and potential treatment of various diseases and debilitating disorders, as well as fundamental biomedical knowledge. The diseases and debilitating disorders include “Lou Gehrig’s disease” (amyotrophic lateral sclerosis, or ALS), Parkinson’s disease, Alzheimer’s disease, spinal-cord injury, cancer, cardiovascular diseases, diabetes, and rheumatoid arthritis. The necessary research would entail transfer of human somatic cell nuclei into enucleated human eggs for the purpose of deriving blastocysts and embryonic stem cells and stem cell lines; there would be no implantation in a uterus. Some have expressed concern that this research might nevertheless be misdirected to human reproductive cloning. If our recommendation is adopted, the development and birth of a newborn would be criminalized by a legally-enforceable ban on any such attempts at implantation. The committee that produced the report from the National Academies entitled Stem Cells and the Future of Regenerative Medicine considered a wide range of views on the ethical and societal issues involved in the production of human embryonic stem cells—including nuclear transplantation technology [2]. After carefully considering all sides of the issue, that committee produced the following conclusion and recommendation concerning this technology: Conclusion: Regenerative medicine is likely to involve the implantation of new tissue in patients with damaged or diseased organs. A substantial obstacle to the success of transplantation of any cells, including stem cells and their derivatives, is the immunemediated rejection of foreign tissue by the recipient’s body. In current stem cell transplantation procedures with bone marrow and blood, success hinges on obtaining a close match between donor and recipient tissues and on the use of immunosuppressive drugs, which often have severe and potentially life-threatening side effects. To ensure that stem cell-based therapies can be broadly applicable for many conditions and people, new means of overcoming the problem of tissue rejection must be found. Although ethically controversial, the somatic cell nuclear transfer technique promises to have that advantage. Other options for this purpose include genetic manipulation of the stem cells and the development of a very large bank of ES cell lines [2].

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Scientific and Medical of Aspects: Human Reproductive Cloning Recommendation: In conjunction with research on stem cell biology and the development of potential stem cell therapies, research on approaches that prevent immune rejection of stem cells and stem cell-derived tissues should be actively pursued. These scientific efforts include the use of a number of techniques to manipulate the genetic makeup of stem cells, including somatic cell nuclear transfer [2]. Our panel includes members who participated in the workshop held at the National Academies on June 23, 2001. This workshop was convened as part of the data-gathering process for the separate committee that produced the above report focused on stem cells. We have also conducted our own extensive literature review and consulted with many of the world’s leaders in nuclear transplantation to produce stem cells in our own workshop held on August 7, 2001—including I. Wilmut, R. Jaenisch, R. Yanagimachi, J. Cibelli, P. Mombaerts, and A. Trounson (see Appendix C). Based on this review and discussion, the panel determined that although there is a clear therapeutic potential for techniques in which stem cells are produced through nuclear transplantation (as in Figure 2), this potential is nascent and needs considerable research. As described in Chapter 2, the potential of this research also includes developing a broader understanding of how human tissue cells develop normally, and how human diseases that have a genetic component are caused at a cellular level. THE PANEL’S CONCLUSIONS AND RECOMMENDATIONS The panel has examined and analyzed the scientific, medical, and legal literature on the issue, and heard testimony at a workshop from experts in animal cloning, assisted reproductive technologies, and science, technology, and legal policy—including people who, on scientific and medical grounds, either oppose or defend human cloning. After carefully considering the issues raised, we conclude that the case has not been proven that human reproductive cloning would lead to fewer negative outcomes at this time than reproductive cloning in other mammals, and we make the following recommendations: Human reproductive cloning should not now be practiced. It is dangerous and likely to fail. The panel therefore unanimously supports the proposal that there should be a legally enforceable ban on the practice of human reproductive cloning. For this purpose, we define human reproductive cloning as the placement in a uterus of a human blastocyst derived by the technique that we call nuclear transplantation. In reaching this con-

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Scientific and Medical of Aspects: Human Reproductive Cloning clusion, we considered the relevant scientific and medical issues, including the record from cloning other species, and the standard issues that are specifically associated with evaluating all research involving human participants. The scientific and medical considerations related to this ban should be reviewed within 5 years. The ban should be reconsidered only if at least two conditions are met: (1) a new scientific and medical review indicates that the procedures are likely to be safe and effective and (2) a broad national dialogue on the societal, religious, and ethical issues suggests that a reconsideration of the ban is warranted. Finally, the scientific and medical considerations that justify a ban on human reproductive cloning at this time are not applicable to nuclear transplantation to produce stem cells. Because of its considerable potential for developing new medical therapies for life-threatening diseases and advancing fundamental knowledge, the panel supports the conclusion of a recent National Academies report that recommended that biomedical research using nuclear transplantation to produce stem cells be permitted. A broad national dialogue on the societal, religious, and ethical issues is encouraged on this matter. SUMMARY This panel was charged with assessing the scientific and medical evidence surrounding human reproductive cloning. Most of the relevant data on reproductive cloning are derived from animal studies. The data reveal high rates of abnormalities in the cloned animals of multiple mammalian species and lead the panel to conclude that reproductive cloning of humans is not now safe. Our present opposition to human reproductive cloning is based on science and medicine, irrespective of broader considerations. The panel stresses, however, that a broad ethical debate must be encouraged, so that the public can be prepared to make decisions if human reproductive cloning is some day considered medically safe for mothers and offspring. The panel’s discussion inevitably included a comparison of the methods used for reproductive cloning and nuclear transplantation to produce stem cells. The panel is in agreement with the recent report from the National Academies entitled Stem Cells and the Future of Regenerative Medicine [2] in affirming the potential for studies on stem cells isolated through nuclear transplantation. The probable benefits include advances in funda-

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Scientific and Medical of Aspects: Human Reproductive Cloning mental biomedical knowledge, as well as the understanding and treatment of various diseases and debilitating disorders. REFERENCES 1. NATIONAL BIOETHICS ADVISORY COMMISSION. Cloning Human Beings, Volume I: Report and Recommendations of the National Bioethics Advisory Commission. Rockville, MD. 1997 Jun. Online at: http://bioethics.gov/pubs/cloning1/cloning.pdf. 2. COMMITTEE ON STEM CELLS AND THE FUTURE OF REGENERATIVE MEDICINE, BOARD ON LIFE SCIENCES AND BOARD ON NEUROSCIENCE AND BEHAVIORAL HEALTH. Stem Cells and the Future of Regenerative Medicine. Report of the National Academy of Sciences and the Institute of Medicine. 2001 Sep.