Exploring the Ethical Boundaries on
Genomic and Genetic Research
National Human Genome Research Institute
July 22, 2002
This workshop explored the ethical and policy challenges raised by genetic science in four areas: reproductive genetic testing, cloning/stem cell research, germline gene transfer and genetic enhancement. The goal of the workshop was to discuss major issues at the intersection of science and medical ethics to determine what ethical, legal and social implications (ELSI) research and policy development these areas might require. The workshop also endeavored to determine what role, if any, the National Human Genome Research Institute (NHGRI) might play in addressing these issues.
NHGRI Director Dr. Francis S. Collins, and meeting Chair Jeffrey Botkin, of the University of Utah, welcomed the participants and discussed what they hoped the meeting would accomplish. Dr. Collins explained that, as has been true since the beginning of the Human Genome Project, in thinking about the future of genomic research, it remains critically important to consider the ELSI issues that accompany the biomedical science. He described what he thought was meant by "boundaries on research." He noted that many presume that science moves on regardless of the ethical issues. He suggested that science is designed to explore the unknown, and that we should not assume that science applications occur without societal implications. Dr. Collins concluded by urging the group to be concrete in its recommendations for future National Institutes of Health (NIH) research on these topics and in identifying opportunities for policy consideration.
Dr. Botkin asked the group to focus on the possible research priorities for the four topic areas. He then discussed the controversial nature of the topics and the need to base ethical analysis on facts. He noted that conducting ELSI research before a technology has been fully developed is a challenge. From his perspective, the day's discussion would ultimately focus on children and their health. Dr. Botkin suggested that the NHGRI ELSI program is a significant asset to better understanding the societal implications of science research, so much so that other NIH institutes are now beginning to create similar programs.
Dr. Joe Leigh Simpson described the current state of reproductive genetic testing. Tests are used for diagnostic purposes early in pregnancy, in order to give women reproductive options. He discussed the risks involved with some tests, including amniocentesis and pre-implantation genetic diagnosis (PGD). Dr. Simpson predicted that PGD will be increasingly utilized to detect Mendelian disorders and translocations. He added that if a limit existed on the number of embryos that would be transferred, PGD would become attractive and almost ineluctably be chosen by patients to increase pregnancy rates. Then, the capacity may not exist nationwide to offer this service. He foresaw increased screening for genetic markers that are predictive for implantation and pre-implantation embryos. These screening techniques may also play a role in gene-transfer experiments.
Dr. Nancy Press discussed the policy issues associated with the two types of reproductive genetic testing - late (or established) pregnancy testing and early (or pre-pregnancy) testing. A number of concerns about late prenatal testing have been raised, including: issues of abortion, effects on people with disabilities, impact on women and the experience of pregnancy, and effects on the family. She raised a number of questions about how such tests should be administered, for example who should have access to them and how they should be regulated and marketed.
The workshop participants then identified several aspects of reproductive genetic testing worth further consideration:
- Understanding the underlying values of the public about reproductive genetic testing, as assessing patient understanding and use of these technologies is necessary to get a sense of their ethical limits.
- Using a more rapid grant process to study these issues.
- Access to these technologies.
- A disability perspective on this field.
- More conversations with interested parties.
Dr. John Gearhart described the current state of stem cell research. He began with a review of the definition of stem cells. He then described the many scientific issues that must be worked out in order for this technology to be practical, including staging modalities, tumorigenesis, immune response, tolerance, genetic alterations, and nuclear/cellular reprogramming. He presented an experiment in mice that dramatically showed the effects of stem cells, but stated clearly that there is a long way to go to translate that work into treatments for humans.
Dr. Gearhart then discussed reproductive cloning. He cited the need for perfection without experimentation as a problem with attempting such cloning. In other words, given safety concerns, one would have to perfect human cloning before attempting it. He added that the hope is that nuclear transfer will overcome problems of immune rejection in stem cell therapy, but that we do not know whether that will be successful. He further noted that we need to learn a great deal more about cell reprogramming before cloning can be used in humans.
Dr. Laurie Zoloth described several reasons why the issues of stem cell and cloning research have caught the imagination of the public and bioethicists. She wondered why religious and philosophical arguments are so dominant in this debate, and asked if science should be a matter of ethics or of politics. She suggested that we now confront new and contested science in part because the science is uncertain. Dr. Zoloth noted that there is disagreement as to who should decide whether particular aspects of science should proceed. She also argued that combining stem cells and cloning in the same debate has muddled the discussion. She offered several questions that could be addressed by ELSI research and provided policy options for addressing some of these questions.
The workshop participants suggested several positions regarding this topic:
- There was grave concern about the NHGRI funding ELSI/Policy research in the area of cloning/stem cell research.
- NHGRI ELSI scholarly work should be done before moving toward policy recommendations.
- There is a need for NHGRI to educate the public on the science of these technologies; for instance, explaining what making a genetic copy is and is not.
Dr. Gerald Schatten described the current state of the science of germline gene transfer. Among topics included under this category are: Assisted Reproductive Technologies (ART), transgenesis, gene therapy, genetic enhancement, embryonic stem cells, and cloning.
While scientific research has focused on transgenic mouse models, Schatten stressed the "missing link" between mouse models and human patients. He also discussed the difference between human and primate embryonic development. He noted that, because science is making new forms of human development possible, children have been born with two sets of mitochondrial mothers. Schatten added that ART has assisted many couples, but people are still concerned about issues of safety. He suggested a need for an "ART Silamar" conference to explore the need for regulation in this area. The meeting would address relevant issues about ART, such as what are and are not the facts as well as what is acceptable, unacceptable and experimental. He also suggested that there be discussion of raising standards in genetic counseling.
Dr. Amy Patterson defined human gene transfer, or gene therapy, and discussed the significant safety and ethical concerns in this area. These include concerns about modification of the human genome (i.e., vertical "germline" transmission), safety risks and controversial applications (such as enhancements). She suggested that the main concern in proceeding with this technology is genetic alteration of reproductive cells that change the genes transmitted to offspring. Will there be negative consequences for future generations if such gene transfer occurs? Patterson also articulated the difference between intentional and inadvertent gene transfer. A 2001 study found evidence for the distribution of vector DNA after gene transfer therapy in two male patients' sperm, which poses great concern. The Recombinant DNA Advisory Committee (RAC) of the National Institutes of Health (NIH) is now working to respond to issues concerning protocols that involve inadvertent gene transfer. Through the RAC, NIH will explore scientific and ethical aspects of this research. She believes that inadvertent gene transfer falls into a policy "gray zone," because for the most part, policies are not developed regarding unintentional actions of scientists.
The group suggested several possible areas for ELSI research and policy development in this arena:
- Clarifying the definition of germline gene therapy.
- Collecting data on the reproductive outcomes of gene transfer subjects, which could help policy makers address the likely scenarios/adverse events that might result from this technology.
- Further review of intentional germline gene transfer as a possible therapy.
- Policy development regarding inadvertent gene transfer.
Dr. Lee Sweeney described the science behind genetic enhancement. He cited his own work involving injections of growth hormone in mice as an example of how genetic therapy could be used to enhance athletic performance. The intent of such work is to expand muscle growth and regeneration through production of Insulin-like Growth Factor I (IGF-I). He found that IGF-I over-expression promotes skeletal muscle hypertrophy in younger mice, prevents muscle loss in older mice, and leads to greatly improved repair and function of dystrophic muscles. IGF-I or similar gene transfer in skeletal muscle might someday be used for genetic enhancement of human athletic performance, which could have profound effects on sports at all levels.
Dr. Eric Juengst described the current state of public policy discussions regarding genetic enhancement. He noted that, currently, there is not a major policy debate regarding genetic enhancement. He suggested the need to distinguish between enhancement and treatment as a matter of policy, which he thought would prove difficult. He also pointed out that, once the distinction is made, it would still be unclear as to how enhancements should be regulated. Dr. Juengst stated that there is a need to define medical boundaries, such as limits on off-label usage. He pointed out that NHGRI could help to develop a public dialogue on this subject, support policy development in this area and be an arbiter of sound medical practice regarding genomics.
The workshop participants suggested a few specific items for further consideration:
- Finding a new mechanism for redefining genetic enhancement. Reaching a consensus about the difference between experimental therapy and enhancement.
- Enabling the broader community, including industry, to reach consensus regarding therapy and enhancement.
- Developing a collaborative conference with the American Society of Gene Therapy and commercial sponsors focusing on the definitional issues.
- Defining what is meant by aging
This workshop provided the NHGRI helpful ideas about which questions ELSI research should address. It provided fewer insights regarding public policy development, but suggested that:
- The NHGRI should, for the most part, avoid policy development related to cloning or stem cells.
- The time is not ripe for policy development regarding genetic enhancements.
- Policy development in the area of reproductive genetic testing would clearly have to involve many other organizations, and it could prove difficult for the NHGRI to play a leading role in this area. On the other hand, this meeting was unique in that it brought people together to discuss reproductive genetic testing who almost never meet, and the NHGRI might serve a similar useful role as a convener in the future.
- Germline gene transfer appears not to be a viable technology at present, given issues of safety. However, the time required for the technology to mature may provide an opportunity to develop policy in this area before it becomes a viable therapy. Clearly, work needs to occur in the area of inadvertent gene transfer. The NHGRI might consider working with other NIH institutions, including the RAC, on this issue.
This meeting helped clarify the NHGRI's role in these four topic areas. One major theme that came out of this workshop, as with other NHGRI planning workshops, was the need to educate the public further, specifically regarding each of these four topics. Ultimately, this meeting not only pointed out the need for boundaries on research, but the need for the NHGRI to place boundaries on the topics it chooses to address, in both ELSI research and public policy development.
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Last Reviewed: December 2005