Human Germline Genetic Modification: Issues and Options for Policymakers

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Genetics and Public Policy Center
Germline genetic modification is possible in animals, but not yet in humans. If certain technical obstacles were overcome, human germline genetic modification (HGGM) could allow human beings to create permanent heritable genetic changes in their descendants by changing the genetic makeup of human eggs or sperm, or human embryos at the earliest stages. For many decades, the technical barriers to HGGM have seemed insurmountable. Today, however, advances in human reproductive technologies, stem cell science, and animal genetic modification have brought the possibility of HGGM much nearer than it has been before. The Genetics and Public Policy Center believes it is time for renewed consideration of this controversial subject. This report, Human Germline Genetic Modification: Issues and Options for Policymakers, analyzes the scientific, legal, regulatory, ethical, moral, and societal issues raised by genetic modification of the human germline, provides data about the American public’s views about HGGM, and explores possible policy approaches in this area. Science Germline genetic modification is possible in laboratory animals, and some techniques could be translated for use in humans although none has been tried. Scientists are able to replace a faulty gene with a “normal” copy in mouse embryonic stem cells, then introduce those stem cells into an early mouse embryo where they can give rise to genetically modified sperm or eggs. The next generation of mice that results from the modified sperm or eggs will contain the “normal” copy of the gene. It is now possible to replace a gene in human embryonic stem cells, overcoming a huge obstacle to HGGM. In addition, scientists have been able to derive genetically modified sperm directly from mouse stem cells. Together, these developments suggest that HGGM may not be as far off as we thought even five years ago. While advances in these techniques have been driven by more general research goals widely viewed as valuable, and not the pursuit of HGGM specifically, these discoveries will catapult us over what were understood to be the principal technical obstacles to HGGM. Safety Serious consideration of safety is and has been of utmost importance in any deliberation about HGGM. In animal research, many germline genetic modification approaches can introduce unwanted mutations that can lead to severe developmental outcomes, even death. Most safety risks of HGGM would be to the resulting child. The proposed techniques for HGGM involve extensive manipulation of stem cells, eggs, sperm, or embryos in the laboratory prior to introduction into a woman’s uterus. Such manipulation alone could alter the growth and development of the fetus in ways that are not yet well understood, resulting in health problems that in many cases could be lethal. There is a clear need for more animal research and better data, although it is less clear how much and what it would need to show. Many questions exist about how to measure the risks and benefits of HGGM. And although it is a basic tenet of medical practice that patients receiving medical treatment must provide informed consent, opinions are divided as to whether and when the consent of the true “patients” — the future child and future generations — could and should be assumed. Scenarios HGGM may become more technically feasible in the future. The question remains whether and for what purpose HGGM would be attempted. Many first applications could be imagined for HGGM and the technical feasibility and perceived demand are different for each. An example of a technically more feasible use of HGGM with low demand would be its use to prevent recessive genetic disease such as cystic fibrosis. This is more technically feasible because the single-gene mutations have been identified. However, since these diseases can be avoided by other already existing techniques, such as PGD, the perceived demand for using HGGM would be low. An example of a technically less feasible use of HGGM with unclear demand would be its use to enhance traits such as intelligence or strength. This is less technically feasible because the genetics behind these traits are largely unknown. The perceived demand is unclear because of the many ethical questions surrounding the use of HGGM for enhancement. In contrast, there may be fewer ethical objections to — and more demand for — using HGGM to enhance human health, to provide a “vaccine” against HIV for example. Feasibility would depend on both an understanding of the genetic disease at issue and the overall development of safe and efficient methods for HGGM. A table analyzing eight possible scenarios for HGGM is presented in the report. Public Opinion Until now, the most sustained and visible deliberations about HGGM have been within elite governmental commissions or academic institutions. Frequently, these groups have called for increased public input in the discussion, but there has been little public engagement in the issue outside of the extreme portrayals of HGGM by Hollywood or the popular press. As a result, little has been known about the views of the general public. In order to learn more about what the American public knows, thinks, and feels about HGGM and other reproductive genetic technologies, the Genetics and Public Policy Center recently conducted a broad survey of 4,834 Americans. Our data show significant interest in HGGM as a potential means for avoiding serious genetic disease. However, concerns were expressed about how safe the technology would be, who would have access to it and who would not, and the impact of HGGM on society as a whole. Ethics The purposes for which HGGM might be attempted vary, from “fixing” a genetic mutation before an individual is born to enhancing children with socially desirable traits such as athletic skill or intelligence. Views differ as to which purposes are ethically acceptable and whether it is possible to meaningfully distinguish, for example, between a “therapeutic” use of HGGM on the one hand and an “enhancement” use on the other. A vast array of ethical issues arises from HGGM. HGGM raises both the specter of humans “playing God” and questions about whether such interventions in nature would change the human gene pool, ultimately affecting the species as a whole. There are fears that HGGM will negatively affect human dignity and attitudes towards those living with disabilities, casting people as “problems” that could have been avoided and putting pressure on families to have genetically “perfect” children. Some question whether HGGM would start society on a slippery slope to a modern version of eugenics, regardless of the purposes for which it would be used. And for those who categorically oppose manipulation or destruction of human embryos, HGGM would be unacceptable under any circumstances because it would involve one or both for the foreseeable future. Oversight In the United States, both the Food and Drug Administration (FDA) and the Recombinant DNA Advisory Committee (RAC) of the National Institutes of Health (NIH) play a role in current federal oversight of HGGM. FDA has indicated that it would treat any proposals for HGGM the same way it treats proposals for somatic gene modification, and require an investigational new drug application (IND) to be filed before the technology may be attempted in humans. It is unclear what criteria FDA would use to evaluate such an application. At the present time, the RAC has indicated that it will not consider any proposals for HGGM. Options An array of policy approaches is available for future oversight of HGGM. Policymakers and the public may consider a direct ban of HGGM; increased oversight with an eye towards safety, ethical use, or both; or promotion of HGGM by providing additional resources for relevant research. International laws, United States law and regulation, and voluntary self-regulation by scientists are some of the approaches that are described, along with the advantages and disadvantages of each. Although HGGM remains on the distant horizon, technologic advances are bringing HGGM from the imaginable to the possible. Thus it is time to consider the difficult questions about HGGM. An enriched and expanded discussion that includes both experts and the public offers an opportunity to share information and understanding about the underlying values and concerns that inform our individual and collective perspectives on HGGM. Such an approach ultimately will lead to thoughtful and robust public policies.
Public Policy, Germ-Line Mutation, Ethics