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PERSPECTIVES Links ENCYCLOPEDIA OF LIFE SCIENCES Plant 16. breeding and crop improvement 17. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. Turning Point Project. Who plays God in the 21st century? (Paid Advertisement by Turning Point Project on behalf of 19 non-governmental organizations). The New York Times A11 (New York, 11 October 1999). The Crucible II Group. Seeding Solutions Volume 1. Policy options for genetic resources (People, Plants, and Patents revisited) (International Plant Genetic Resources Institute (IPGRI) and Dag Hammarskjöld Foundation (DHF), Rome & Upsala, 2000). Darwin, C. The Origin of Species (Penguin Books USA Inc., New York, 1958). Darwin, C. The Effects of Cross and Self Fertilization in the Vegetable Kingdom (New York Univ. Press, New York, 1989). Crabb, R. The Hybrid Corn-Makers (West Chicago Publishing Company, West Chicago, Illinois, 1993). Smith, D. C. in Plant Breeding: A Symposium Held at Iowa State University (ed. Frey, K. J.) 3–54 (The Iowa State Univ. Press, Ames, Iowa, United States, 1966). Wallace, H. A. & Brown, W. L. Corn and Its Early Fathers (Iowa State Univ. Press, Ames, Iowa, USA, 1988). USDA/NASS. Iowa Agricultural Statistics (NASS/USDA, Washington DC, 1997). Hallauer, A. R. & Miranda, J. B., Fo. Quantitative Genetics in Maize Breeding (Iowa State University Press, Ames, Iowa, United States, 1988). Fitzgerald, D. The Business of Breeding (Cornell Univ. Press, Ithaca and London, 1990). Jones, D. F. in National Academy of Sciences of the United States of America, Biographical Memoirs Vol. XXIII 217–233 (Natl Acad. Sci., Washington, 1945). Shull, G. H. The composition of a field of maize. American Breeders’ Association Report 4, 296 (1908). Jones, D. F. The effects of inbreeding and cross-breeding upon development. Connecticut Agricultural Experiment Station Bulletin (1918). Coors, J. G. & Pandey, S. (eds) Genetics and Exploitation of Heterosis in Crops (American Society of Agronomy, Inc., Crop Science Society of America, Inc., Madison, 1999). Duvick, D. N. in Maize Seed Industries in Developing 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. Countries (ed. Morris, M. L.) 103–211 (Lynne Rienner Publishers, Inc. and CIMMYT, Boulder, Colorado (USA) and México, D. F. (Mexico), 1998). USDA. Agricultural Statistics (various issues). (USDA, Washington DC, 1944). Russell, W. A. Genetic improvement of maize yields. Advances in Agronomy 46, 245–298 (1991). Duvick, D. N. Genetic contributions to advances in yield of U. S. maize. Maydica 37, 69–79 (1992). Castleberry, R. M., Crum, C. W. & Krull, C. F. Genetic yield improvement of U. S. maize cultivars under varying fertility and climatic environments. Crop Sci. 24, 33–36 (1984). USDA/NASS. Crops Production Data, by States, 1866–1997 (USDA/NASS, Washington, DC, 2000). Cardwell, V. B. Fifty years of Minnesota corn production: sources of yield increase. Agronomy J. 74, 984–990 (1982). Duvick, D. N. in The Genetics and Exploitation of Heterosis in Crops (eds Coors, J. G. & Pandey, S.) 19–29 (American Society of Agronomy, Inc., Crop Science Society of America, Inc., Soil Science Society of America, Inc., Madison, Wisconsin, 1999). Turning Point Project. Biotechnology = Hunger (Paid Advertisement by Turning Point Project on behalf of 22 non-governmental organizations). The New York Times A5 (New York, 8 November, 1999). Goldburg, R., Rissler, J., Shand, H. & Hassebrook, C. Biotechnology’s Bitter Harvest —Herbicide Tolerant Crops and the Threat to Sustainable Agriculture (The Biotechnology Working Group/The Tides Foundation/Environmental Defense Fund, New York, New York, 1990). van Dommelen, A. Hazard Identification of Agricultural Biotechnology: Finding Relevant Questions (International Books, Utrecht, the Netherlands, 1999). Duvick, D. N. Genetic diversity in major farm crops on the farm and in reserve. Economic Botany 38, 161–178 (1984). Duvick, D. N. in Developing Drought- and Low N-Tolerant Maize Proceedings of a Symposium, March 25-29, 1996, CIMMYT, El Batan, Mexico. (eds Edmeades, G. O., Bänziger, M., Mickelson, H. R. & Peña-Valdivia, C. B.) 332–335 (CIMMYT, México, D. F., 1997). Tollenaar, M., McCullough, D. E. & Dwyer, L. M. in Genetic Improvement of Field Crops (ed. Slafer, G. A.) 183–236 (Marcel Dekker, Inc., New York-Basel-Hong Kong, 1994). SCIENCE AND SOCIETY Human embryonic stem cell research: ethical and legal issues John A. Robertson The use of human embryonic stem cells to replace damaged cells and tissues promises future hope for the treatment of many diseases. However, many countries now face complex ethical and legal questions as a result of the research needed to develop these cell-replacement therapies. The challenge that must be met is how to permit research on human embryonic tissue to occur while maintaining respect for human life generally. Embryonic stem (ES) cell research offers the hope of cell-replacement therapy for diseases such as Parkinson disease, diabetes and cardiac myopathy, but formidable scientific and clinical challenges must be over- 74 come before such therapies could become available1,2. For example, scientists need to learn how to direct pluripotent ES cells to differentiate into the required cell or tissue type3. Clinicians must then determine the transplanted cells’ immune compatibility with the host, and where, and in what amounts, to replace cells in diseased organs to achieve a therapeutic effect. These scientific efforts are also complicated by ethical concerns about obtaining human ES cells from aborted fetuses or from the destruction of early human embryos. The resulting controversy has delayed or stopped human ES cell research in some countries, and could affect the extent to which human EScell derived therapies are developed and used. This article will survey the main ethi- | JANUARY 2001 | VOLUME 2 cal and legal issues that arise from human ES cell research, and how public policy should accommodate them. Legality of human embryo research Legal treatment of the use of human fetal tissue or the destruction of human embryos to obtain ES cells for research varies widely throughout the world. The United States, the United Kingdom and many other countries permit the use of human fetal tissue for research when a woman’s decision to donate fetal tissue is clearly separate from the decision to abort. Although most American states permit ES cell research that requires the destruction of human embryos, federal law prohibits the direct funding of embryo destruction to obtain such cells4,5. However, federal law permits the funding of research on human embryonic tissue that has been derived with private funds, provided that guidelines for how these cells should be derived have been followed6. Although the United Kingdom at present only permits human embryos to be used to study infertility, contraception and birth defects, an expert group at the Department of Health has recommended that embryo research involving cell-based treatments be added to the list of acceptable purposes 7. Germany and France prohibit destructive embryo research, whereas other European Union members are split on the question8,9. Australia also has a mixture of positions, with the state of Victoria specifically banning “destructive embryo research” that produces ES cells for research10, whereas the states of New South Wales and Queensland permit it according to the guidelines of the Australian Medical Research Council11. A legal ban on destroying human embryos to produce ES cells, however, does not mean that research on ES cells legally derived in another jurisdiction is also prohibited. The United States Congress’ ban on federal funding of human embryo research restricts only federal support for the derivation of human ES cells. The ban does not affect research on human ES cells that have been derived by using private funds, provided that National Institutes of Health (NIH) regulations for how those cells were derived have been observed6. Similarly, human ES cell research is now occurring in Victoria, despite its ban on embryo destruction, with cells derived in Singapore where their destructive derivation is legal. Some countries or states, including Michigan in the United States12 and Victoria in Australia, now ban human cloning without drawing a distinction between cloning www.nature.com/reviews/genetics © 2001 Macmillan Magazines Ltd PERSPECTIVES a b Nuclear transfer Adult cell c Oocyte activation and development Enucleated oocyte Nucleus of adult cell Inner cell mass d Culture and differentiate cells in vitro Trophoblast Blastocoel Figure 1 | Somatic-cell nuclear cloning for therapeutic purposes. a | A nucleus from an adult cell is removed and dedifferentiated in vitro. b | It is then transferred to an enucleated oocyte, which is activated so that it grows in vitro to the blastocyst stage. c | At this stage, cells from the inner cell mass would be harvested and cultured in vitro to select embryonic stem (ES) cells. d | ES cells would then be differentiated in vitro to form a cell type or tissue that the patient needs. for reproductive or for therapeutic purposes. If clinical research shows that immunologically competent ES cells could aid the treatment of certain diseases, such as diabetes or Alzheimer disease, these legal bans could prevent the use of nuclear-transfer cloning (FIG. 1) to produce such cells. However, both the Council of Europe’s Convention on Human Rights and Biomedicine, and UNESCO’s Universal Declaration on the Human Genome and Human Rights have been careful to recommend the banning of only reproductive cloning, thereby avoiding this problem. Ethical status of human embryos If pluripotent stem cells could be obtained from adult tissues, as some research suggests, an important source of ethical conflict would vanish13. However, when stem cells are obtained from preimplantation human embryos, ethical objections arise from the need to destroy embryos to obtain those cells. Those who believe that preimplantation human embryos are themselves persons or subjects with rights are against the destruction of embryos for research, whereas those who view the embryo as too rudimentary in development to have an inherent moral status generally permit this research. Although the conflict between these positions might ultimately be unresolvable, two sets of distinctions are helpful to negotiate the terrain between them. Symbolic versus rights issues. An important distinction in this ethical and legal debate is whether objections to human ES cell research rest on rights-based or symbolic grounds. Those who view the human preimplantation embryo as a person or subject with rights and interests believe that the intentional destruction of an embryo is equivalent to murder. If that position is correct then the beneficial goal of saving or prolonging life would not matter, for no life may be taken to preserve the life of one or even many persons (except in cases of self-defence, war and dire necessity). Although some religions, and many people, take this position, it conflicts with widely held philosophical and moral views that hold that status as a person or as an entity with interests requires, at the very least, a nervous system capable of sentience, if not also of cognition and consciousness14–16. The neural development that is essential to have inherent moral status and interests in one’s own right is not present in the undifferentiated cells of preimplantation embryos. The earliest differentiation in the embryo is towards TROPHOBLASTIC tissue, after which the INNER CELL MASS forms — it is from these cells that the embryo proper develops and from which ES cells are derived17. Only after implantation in the uterus does the embryo proper begin to establish its body plan, events that are later followed by the development of the nervous system. Because of the preimplantation embryo’s rudimentary state of development, removing ES cells from the inner cell mass of human BLASTOCYSTS does not wrong them, and so should be permitted. Denial of the early embryo’s inherent moral status and of the correlative moral duty not to destroy embryos does not, however, mean that the human embryo is perceived as being without value, or that it may then be treated like any other excised human tissue. An object or thing can be invested with meaning, even if it lacks rights or interests in itself, as occurs with religious objects, monuments, works of art or even parts of nature. Many people, for example, reject the view that the embryo is a person but believe that the embryo is different from ordinary human tissue because of the unique potential it has to develop into a new human being. Sometimes described as ‘special respect,’ this attitude towards human embryos shows or symbolizes our respect for human life generally14,18–20. NATURE REVIEWS | GENETICS The desire to make a symbolic commitment to non-rights-bearing entities, such as human embryos, depends on the entity and context involved. In the context of in vitro “Those who view the human preimplantation embryo as a person or subject with rights and interests believe that the intentional destruction of an embryo is equivalent to murder.” fertilization (IVF) treatment, for example, the generation of more embryos than can be safely transferred to the uterus is widely accepted as not being unduly disrespectful of human life, because it enables children to be born to infertile couples. Similarly, destroying embryos that are left over from IVF procedures to develop cell-replacement therapies should also be ethically acceptable, for the goal of treating disease and saving life justifies the symbolic loss that arises from destroying embryos in the process. By contrast, selling human embryos or using them in cosmetic-toxicology testing seems to be disrespectful of the symbolic meaning that many people attach to embryos because those uses fulfil no life-affirming, or other important, purpose. The distinction between rights/duties and symbols explains many of the laws and regulations that exist in countries that permit embryo research. In the United Kingdom, for example, embryos may be used in research but only for specified purposes. Many countries, such as the United VOLUME 2 | JANUARY 2001 | 7 5 © 2001 Macmillan Magazines Ltd PERSPECTIVES States, permit unlimited research in the private sector but ban or strictly limit human embryo research that is funded by the government. Both the 1994 report of the NIH Human Embryo Research Panel and the 1999 report of the United States National Bioethics Advisory Commission rejected the idea that the embryo is a person or moral subject in its own right but, at the same time, restricted certain kinds of human embryo research. They put in place special consent and review procedures that can be interpreted as a form of symbolic or ‘special respect’ for human embryos21,22. Two kinds of complicity. A second important ethical distinction is the difference between causative and beneficial complicity. A legal ban on destroying human embryos to obtain ES cells need not constitute a ban on conducting human ES cell research with ES cells derived elsewhere, if that derivation would have occurred regardless of a particular later use. Recognition of the use versus derivation distinction now informs federal research funding law in the United States6. In other countries, it distinguishes whether embryo research activities are permitted or made criminal, as in Victoria, Australia. As long as some jurisdictions permit destructive embryo research to occur, ES cell lines might be derived that could be used for research in countries that themselves ban the derivation of human ES cells by embryo destruction. This is because the cells lines would have been derived independently of the later decision to use them for research. The distinction between use and derivation is neither cynical nor disingenuous for it reflects the basic distinction in the ethics of complicity between causing an immoral or wrongful act to occur and benefiting from it once it has occurred. One who intends or Glossary TROPHOBLAST CELLS Cells that contribute to the placenta but not to the embryo itself and that are required for an embryo to implant into the uterine wall. INNER CELL MASS Cells that give rise to the embryo proper and that arise from the inner cells of an early preimplantation embryo. BLASTOCYST A preimplantation embryo that contains a fluid-filled cavity called a blastocoel. CLEAVAGE The mitotic divisions of the early embryo that occur in the absence of growth to divide the embryo into many smaller nucleated cells. 76 causes an immoral act to occur is responsible or has complicity in a causative sense, and may be held responsible for the event. Conversely, one who does not proximately cause a wrongful event is not morally responsible for its occurrence, even if he or she later benefits from it. “Because of the preimplantation embryo’s rudimentary state of development, removing ES cells from the inner cell mass of human blastocysts does not wrong them, and so should be permitted.” This distinction explains the general willingness to transplant organs from murder (or suicide) victims, despite the fact that a benefit is being reaped from what is clearly a wrongful act. It also explains national policy in the United States and the United Kingdom for the use of fetal tissue, when procedures were put in place to ensure that the prospect of research use of fetal tissue did not cause the abortion to occur23. The distinction between causing and benefiting from a wrong also explains the United States government’s position that a Congressional ban on federally funded ‘embryo research’ does not ban funding of ‘ES cell research’, because ES cells are not ‘embryos’22. Because researchers at many institutions will produce lines of human ES cells for their own purposes, other researchers can use them without being causatively complicit in their production. Those who reject the line between causative and beneficial complicity often do so for symbolic reasons; for example, they do not want to be associated with what they regard as a prior immoral act. The acceptability of this distinction will affect the willingness of governments that ban human embryo research to allow research with human ES cells derived elsewhere to occur, as will the adoption of procedures to discourage the generation of IVF embryos to meet the demand for human ES cells6. It will also affect the willingness of people to use human ES cell therapies once they are developed. Beyond embryo destruction A different set of ethical issues arises once researchers have learnt safe and effective | JANUARY 2001 | VOLUME 2 ways to direct human ES cells to differentiate into specified cell or tissue types, and to transplant them for therapeutic effect in patients. An important clinical issue at this point will be whether ES cells not derived from the patient will be rejected by the patient’s immune system. If so, one strategy for dealing with this problem would be to use a patient’s nuclear DNA to create an embryo from which ES cells compatible with that patient could then be derived21,22,24 (FIG. 1). If nuclear-transfer cloning were necessary for safe and effective use of ES-cellderived replacement therapies, three additional ethical issues beyond the destruction of left-over embryos to obtain human ES cells would arise. One issue would be ethical concerns about creating human embryos for the sole purpose of destroying them to obtain replacement cells for the patient who provided the nuclear DNA. However, the problem of creating embryos to be destroyed is an ethical problem primarily for those who accept that embryos left over from IVF procedures may be destroyed. People who believe that embryos are persons to whom moral duties are owed would also object to such a practice, but on the grounds that any destruction of an embryo is wrong, not merely the destruction of embryos created to be destroyed for their ES cells. Ethical debates about creating human embryos solely for research have existed since the inception of debates over embryo research 25. One can question, however, whether those concerns are even relevant to generating human ES cells by somatic cell nuclear transfer, for the haplogenomes of gametes are not combined through sexual fertilization to form the blastocyst that provides the ES cells. In addition, there is no intention of culturing the embryo beyond the blastocyst stage, nor of implanting that blastocyst in a uterus for reproduction. Given the asexual means of creating the embryo and the lack of intent of implanting it in the uterus, the embryonic entity produced in these circumstances lacks the reproductive significance that some have argued is the moral basis for valuing early embryos21,26. In any event, the question of the ethical acceptability of creating embryos solely for research or for therapeutic purposes clearly implicates symbolic rather than substantive moral concerns. If one rejects the view that embryos have interests or are the subjects of moral duties, then creating them for research or for therapeutic purposes does www.nature.com/reviews/genetics © 2001 Macmillan Magazines Ltd PERSPECTIVES “Sometimes described as ‘special respect,’ this attitude towards human embryos shows or symbolizes our respect for human life generally.” no further substantive harm to them. Objections to the practice might then be viewed as the symbolic expression of a more generalized commitment to respect for human life14,18,20. Many people, however, would fail to see symbolic harm beyond that already occurring by the destruction for research of left-over IVF embryos. If they accept that embryos lack rights or interests, it becomes difficult to argue that any further significant symbolic harm is caused by creating embryos from a person’s own cells for that person’s therapeutic use. The additional symbolic harm of creating embryos only to destroy them will matter to some people but is not in itself a sufficiently strong ethical argument to justify a legal ban on or to morally condemn nuclear-transfer cloning with the patient’s own cells. Nor should it support a ban on the public funding of this research, because the practice of generating ES cells with a patient’s own DNA to prolong or improve the quality of their life does not imply disrespect for human life generally. A second ethical issue presented by the generation of ES cells from adult somatic cell nuclear DNA is that such a practice could lead to reproductive cloning or to the eventual engineering of an offspring’s characteristics. This objection assumes that all forms of reproductive cloning and genetic alteration would be so antithetical to human values, and would be so likely to occur once ES cell cloning for therapeutic uses was established, that society should give up the considerable benefits of histocompatible, cell-replacement therapy to prevent any such potential uses from occurring. A more reasonable position, reflected in both the Council of Europe’s Convention on Human Rights and Biomedicine and UNESCO’s Universal Declaration on the Human Genome and Human Rights, is that the line between therapeutic cloning and reproductive cloning is so clear that it is not necessary to prevent cloning for therapeutic purposes to prevent reproductive cloning. A third ethical issue that would arise if therapeutic cloning became necessary for effective cell-replacement therapy is the access and cost demands that would then be placed on a health-care system. Such costs might be manageable if cell-replacement therapies turned out to be more cost effective and more efficient than existing therapies and systems of care. An equally serious problem in meeting that demand, however, would be the scarcity of human oocytes needed to receive the patient’s nuclear DNA for this cloning. The cloning of non-human mammals so far has been highly inefficient, often requiring in excess of 100 oocytes to obtain one viable clone24,27. If cell-reprogramming factors could not be extracted from oocytes with which to dedifferentiate a patient’s somatic cells to stem-cell types (which could then be multiplied for therapeutic purposes), the ability to meet the therapeutic demand for oocytes would present an important problem. The ability of live, unrelated donors to meet such a demand is highly unlikely for several reasons: the hormone treatments that stimulate the production of many oocytes imposes a considerable burden on women; surgery is required to retrieve the oocytes; oocyte donations are costly; and ethical problems now surround such donations28. Indeed, even if it became ethically and socially acceptable to pay thousands of unrelated women to undergo repeated cycles of oocyte retrieval for therapeutic uses, the demand for oocytes for therapeutic cloning might still outstrip that supply, leaving many patients dependent on the generosity of their female relations to donate the needed oocytes. A system of safely retrieving and storing ES cells from young, healthy women for their own later use would still leave males in need of live donors. Alternative sources of human eggs might be cadavers or aborted fetuses. Techniques to mature oocytes in vitro so that they could receive transferred nuclei would have to be developed, but little research to perfect such techniques is occurring. If it became possible to mature oocytes in vitro, other ethical issues concerning the use of cadaveric or fetal ovary donations would then have to be faced, such as the risk of non-consensual posthumous reproduction by the cadaveric or fetal donor. A clear legal ban on the use of oocytes from cadaveric or fetal ovaries for reproduction would meet that concern. If the use of oocytes from these sources did not lead to reproduction, their use in cloning for therapeutic purposes should be as acceptable as is the use of other cadaveric or fetal transplants to save or prolong lives. NATURE REVIEWS | GENETICS A third alternative to meet the demand for oocytes would be to use bovine eggs, which are in plentiful supply from slaughterhouses. As reported in the press 29 (although as yet unpublished in the scientific literature), one company has already experimented with transferring human nuclear DNA to enucleated bovine oocytes, and found that development to early CLEAVAGE stages does occur. They hypothesize that proteins in the bovine cytoplasm that activate the human DNA would soon be overwhelmed by human proteins, and therefore would not create a true hybrid, even at the embryonic level. Viewed solely as a way to get the nucleus to express itself to the blastocyst stage, with no transfer to the uterus permitted, bovine eggs might be an ethically acceptable way to supply the oocytes needed to provide many patients with immunologically competent replacement cells. Future prospects Biomedical research and therapy based on human embryonic material present complex ethical, legal and social issues that require careful attention if society is to reap the benefits that these techniques potentially offer to many patients. Those who believe that preimplantation human embryos are already persons or moral subjects with rights have profound and probably insurmountable objections to their destruction to obtain ES cells for research or therapy. However, such a person might not object to all uses of human ES cells if those cells had already been derived for other research or therapeutic purposes and if procedures were in place to discourage the creation of embryos just to produce ES cells. “The goal of treating disease and saving life justifies the symbolic loss that arises from destroying embryos in the process. By contrast, selling human embryos or using them in cosmetic-toxicology testing seems to be disrespectful … because those uses fulfil no life-affirming, or other important, purpose.” VOLUME 2 | JANUARY 2001 | 7 7 © 2001 Macmillan Magazines Ltd PERSPECTIVES Those who do not view embryos as having inherent moral status, however, should see no significant ethical barrier to the derivation of human ES cells from early preimplantation embryos for their use in research or therapy. Those people might still value embryos as important symbols of human life generally but the strength of the desire to use embryos to show respect for human life will vary depending on the therapeutic context or research use. Just as discarding surplus embryos generated in the course of treating infertility is generally acceptable, so deriving ES cells from those embryos before their being discarded should be acceptable as well, for in each case an important human purpose — initiating pregnancy or developing new therapies — is fulfilled. Given the prevalence of such views and the strength of the reasoning underlying them, public policies that permit human ES cell research and therapy to occur should be both ethically acceptable and legally available in many countries. In some countries, however, views against abortion, or politics, might continue to block human ES cell research conducted with private or public funds. Once the science progresses to the point that ES cell-derived replacement therapies are safe and effective, ethical concerns will shift from issues of embryo status and protection to issues of cloning for therapeutic purposes, oocyte supply and access to treatment for all who could benefit from these potentially revolutionary therapies. 78 John A. Robertson, J.D. Law School, 727 East Dean Keeton Street, University of Texas, Austin 78705, Texas, USA. email: [email protected] Links FURTHER INFORMATION Parliament advisory group’s recommendations on therapeutic cloning | The United States Congress’ ban on federal funding of human embryo research | Council of Europe’s Convention on Human Rights and Biomedicine | UNESCO’s Universal Declaration on the Human Genome and Human Rights | United States National Bioethics Advisory Commission 1. 2. 3. 4. 5. 6. 7. 8. 9. Thomson, J. A. et al. Embryonic stem cell lines derived from human blastocysts. Science 282, 1145–1147 (1998). Shamblott, M. J. et al. Derivation of pluripotent stem cells from cultured human primoridial germ cell. Proc. Natl Acad. Sci. USA 95, 13726–13731 (1998). Reubinoff, B. E., Pera, M. F., Fong, C. -Y., Trounson, A. & Bongso, A. Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro. Nature Biotechnol. 18, 399–404 (2000). Andrews, L. State regulation of embryo research, (National Institutes of Health, Papers Commissioned for the Human Embryo Research Panel, Vol. II 1994). Public Law No. 105–277, 112 Stat. 2681 (1998). National Institutes of Health. National Institute of Health Guidelines for Research using Human Pluripotent Stem Cells. Federal Register 65 FR 51976–51981 (2000). Department of Health. Stem Cell Research: Medical Progress with Responsibility A report from the chief medical officer’s expert group reviewing the potential of developments in stem cell research and cell nuclear replacement to benefit human health (London, June, 2000). France: Law No. 94-654 No. 175. 11060–11068 (Journal officiel de la République française, Lois et Decret, 30 July 1994). Germany: Law of 13 December 1990 for the protection of embryos (the Embryo Protection Law), (Bundesgestetzblatt, Part I, 2746–2748, 19 December 1990). | JANUARY 2001 | VOLUME 2 10. The Infertility Treatment Act 1995 (Act No. 63/1995). 11. Szoke, H. in Controversies in Health Law (eds Freckelton, I. & Peterson, K.) 242–243 (Federation, Melbourne, 1999). 12. Michigan Public Acts 108 (Michigan Comp. Laws #333. 16274) (1998). 13. Clarke, D. L. et al. Generalized potential of adult neural stem cells. Science 288, 1660–1663 (2000). 14. Dworkin, R. M. Life’s Dominion: An Argument About Abortion, Euthanasia, and Individual Freedom (Knopf, New York, 1993). 15. Feinberg, J. Harm to Others: The Moral Limits of the Criminal Law (Oxford Univ. Press, New York, 1986). 16. Tooley, M. Abortion and infanticide. Phil. Pub. Affairs 2, 1–31 (1972). 17. Grobstein, C. The early development of human embryos. J. Med. Phil. 10, 213–220 (1985). 18. Robertson, J. A. Children of Choice: Freedom and the New Reproductive Technologies (Princton Univ. Press, Princeton, 1994). 19. American Fertility Society. Ethical considerations in the use of new reproductive technologies. Fertil. Steril. 46, S5–S7 (1986). 20. Robertson, J. A. Symbolic issues in embryo research. Hastings Center Report 25, 37–38 (1995). 21. Ad Hoc group of consultants to the advisory committee to the Director, NIH. Report of the Human Embryo Research Panel. (National Institutes of Health, Bethesda, Maryland, 1994). 22. National Bioethics Advisory Commission. The Ethical Use of Human Stem Cells in Research (National Bioethics Advisory Commission, Rockville, Maryland, 1999). 23. National Institutes of Health Revitalization Act of 1993, Pub. L. No. 10–43, Sect. 111, 107 Stat. 129 (codified at 42 U. S. C. Sec. 498A). 24. Solter, D. Mammalian cloning: advances and limitations. Nature Rev. Genet. 1, 199–207 (2000). 25. Robertson, J. A. Embryo research. Western Ontario Law Rev. 24, 15–37 (1986). 26. Annas, G. A., Caplan, A. & Elias, S. The politics of human-embryo research — avoiding ethical gridlock. N. Engl. J. Med. 334, 1329–1332 (1996). 27. Lanza, R. P. et al. Extension of cell life-span and telomere length in animals cloned from senescent somatic cells. Science 288, 666–669 (2000). 28. Cohen, C. B. (ed.) New Ways of Making Babies: The Case of Egg Donation (Indiana University, Bloomington, Indiana, 1996). 29. Wade, N. Ethics panel is guarded about hybrid of cow cells. New York Times A7 21 December (1998). www.nature.com/reviews/genetics © 2001 Macmillan Magazines Ltd