AAAS Panel Addresses Science and Policy of Stem Cells and Reproductive Technologies
The best available research supports a “guesstimate” that sometime within the next five to fifteen years, researchers will be able to derive human eggs and sperm from pluripotent stem cells, according to Robin Lovell-Badge of the UK National Institute for Medical Research. Speaking at an American Association for the Advancement of Science panel yesterday on the science, ethics, and policy challenges of deriving human eggs and sperm, or gametes, from pluripotent stem cells, Lovell-Badge emphasized that the scientific hurdles should not be underestimated. Eggs and sperm are very complex cells, and it takes very complex biological processes to make them.
Lovell-Badge further argued that it will probably be extremely difficult to derive eggs that could be used for reproduction from XY (chromosomally male) cells, and even more difficult, if not impossible, to derive sperm that could be used for reproduction from XX (chromosomally female) cells. Nonetheless, the science is worth pursuing because of the difficulty of studying germ cells in vivo, and the potential benefits of being able to study them in vitro.
The AAAS, the Johns Hopkins Berman Institute of Bioethics, and the British Embassy co-sponsored the panel, “The Science, Ethics and Policy Challenges of Pluripotent Stem Cell-Derived Gametes,” which served as a report on the April meeting of the Hinxton Group, an international consortium on stem cells, ethics, and law. Alan I. Leshner, CEO of AAAS, moderated the group, which included Lovell-Badge, PhD, FMedSci, FRS, Head of Division of Stem Cell Biology and Developmental Genetics, MRC National Institute for Medical Research (UK); Ruth Faden, PhD, MPH, Philip Franklin Wagley Professor of Biomedical Ethics and Executive Director, Berman Institute of Bioethics, Johns Hopkins University; and Debra Matthews, PhD, MA, Assistant Director for Science Programs, Berman Institute of Bioethics, and Assistant Professor, Department of Pediatrics, Johns Hopkins University.
Lovell-Badge also mentioned a long list of projected scientific uses of in-vitro derived germ cells and gametes in basic research, including a better understanding of the role of specific genes in biological processes and in vitro genetics. He also explained clinical uses of in vitro derived oocytes and sperm, emphasizing in particular the projected fertility treatments. Those include treatments for premature ovarian failure, post-menopausal women, new methods of contraception, and germ-line gene therapy for patients with defined genetic diseases. He also talked about the possibility of same sex reproduction, but emphasized that the Hinxton Group concluded this would be extremely difficult or even practically impossible.
Ruth Faden discussed the ethical issues and societal implications of the science of stem cell-derived gametes. She began by making a distinction between ethical challenges relating to the methods of undertaking the science and ethical challenges raised by its possible applications. The former are means-related ethical challenges while the latter are end-related. With regards to the means, she noted that in order for this science to proceed at all, there is an unavoidable need to create human embryos solely for research, maintain them at least until the blastocyst stage, and then destroy them. There is no way to get around this because the only way of establishing that two cells are in fact a viable sperm and a viable egg is to observe them joining to form an embryo. Thus, proof of concept requires the creation of embryos for research. Once it is established that they are, in fact, gametes, scientists can then answer many important questions simply by studying the eggs and sperm that have been derived in vitro. Faden pointed out that currently, the only way to produce eggs for research is by hyperstimulation of the ovaries. The technology, if successful, can get around this difficulty and allow the production of eggs for research without having to resort to taking eggs from women.
As far as the ends are concerned, Faden pointed out that again, an unavoidable feature of scientific knowledge is that it can be used for multiple ends, some of which may be socially controversial. While there are clear, uncontroversial, and good outcomes, including the prevention and treatment of infertility and cancers, there are also more societally controversial ends, such as the possibility of germ line genetic modification, genetic enhancement, and the possibility of same sex offspring. Faden emphasized the importance of highlighting the science as we know it and its avenues of application as we go forward. She underlined the need to have a straightforward description and discussion of these issues from the outset, rather than let them come out of the woodworks in unhelpful ways down the line.
Debra Matthews addressed the policy implications of those ethical and societal challenges, pointing out that there is a great deal of variation among societies in their responses to different aspects of this research. She also stressed that the Hinxton Group acknowledges that societies do have the authority to regulate science, and that scientists do have an obligation to follow the law. Within this larger context, however, the Group’s main policy recommendation is that the mere presence of moral disagreement does not in and of itself justify restrictive policy. Instead, it signals a need for debate on the hard issues until a sufficient consensus can inform intelligent policy. The approach that seeks to avoid all difficulties by automatically banning research about which there is moral disagreement is a bad one.
Matthews said that there was broad agreement within the Group that the standard should be demonstrable risks. With regard to pluripotent stem cell-derived gametes, this standard appears to have been met. There are indeed safety concerns relating to the derivation of gametes from stem cells, and this requires strong oversight mechanisms to regulate the research. Initial attempts to implant embryos need to happen within the context of research, she said: sustained follow-up and care of pregnant women, as well as long-term follow-up of their children must happen with the appropriate oversight. Any individual providing tissue, such as skin cells, should give explicit consent in order for that tissue to be useable for de-differentiation and production of eggs or sperm. This is in contrast to current in vitro fertility treatment, where donors do not have to give consent for the use of their sperm or eggs in particular ways. Since IVF was not originally developed in the context of research, there was not the same kind of oversight. Insisting that this work be conducted in the context of research provides the right kind of oversight to regulate it and ensure its safety and ethical acceptability, she said.
In response to questions, panelists made three additional points: first, they pointed out that if we take IVF to be morally acceptable, then it is not clear, once safety issues are addressed, what the difference would be with stem cell-derived eggs and sperm. The panelists argued that where the egg and sperm come from does not in itself make an ethical difference. If we are OK with IVF, we should be fine with IVF using stem cell-derived gametes as long as any residual safety issues have been addressed. They also emphasized that even if this research were never put to reproductive use, whether for safety or for ethical reasons, there is still a value to the science. Finally, they stressed the need for straightforward, transparent, and respectful dialogue about the science and its implications.
Sirine Shebaya is a Greenwall Fellow with the Berman Institute of Bioethics.
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