A friend of mine refuses to vote. He believes that it makes you responsible for what the government does. He shares the belief of the little old lady who is supposed to have declared, "Vote? I never vote. It only encourages them!" As a modern bioethicist might put it, my friend and the little old lady are afraid of "being complicit with suspect norms."
This question of complicity became a live one for me this week as I participated in a Washington. D.C., meeting of the National Human Genome Research Institute (NHGRI). The gathering brought together 50 nationally prominent bioethicists and biomedical researchers to discuss the NHGRI's research priorities. The group was asked to consider ethical and policy research on four hot button issues: reproductive genetic testing, cloning/stem cells, germline gene transfer, and genetic enhancement.
These deliberations are supposed to result in an action plan for the next 10 years of ethical, legal, and social implications research . Since the establishment of the Human Genome Project about 5 percent of all its federal funding has been spent on this sort of research, "making it the largest source of bioethics funding in the world," according to NHGRI Director Francis Collins. The new plan will be issued in April 2003, when the NHGRI expects to publish the completed human genome on the 50th anniversary of Watson and Crick's paper describing the double helix structure of DNA.
Collins opened the meeting by noting that the most frequent question he hears when he speaks in public is, "Where is this all going to stop?" He charged us with considering: "Should there be boundaries on genetic and genomic research? If so, what should they be? Who should define any boundaries? And how can they be enforced?" The meeting's chairman, University of Utah pediatric researcher Jeffrey Botkin, warned that controversy over genetic research could "tear our society apart." He hoped that our deliberations would aim at "limiting the divisiveness that could be catastrophic in the next decades."
The first session was devoted to the burgeoning field of reproductive genetic testing. That includes testing of embryos before implanting them in women's wombs, known as preimplantation genetic diagnosis (PGD), as well as in utero testing of fetuses. Joe Leigh Simpson, chairman of the Department of Obstetrics and Gynecology at Baylor College of Medicine in Texas, surveyed developments in the field and noted that current prenatal testing, if more widely used, could identify 85 percent of fetuses suffering from Down's syndrome in the first trimester. He also noted that some 6,000 healthy babies have been born worldwide as a result of PGD.
Simpson pointed out that PGD is very attractive to couples who are at high risk of passing along genetic diseases to their offspring because they can avoid the painful decision to terminate a pregnancy. Nancy Press, a bioethicist from the Center for Ethics in Health Care at the Oregon Health and Science University, noted that there are now some 300 different genetic tests available to prospective parents. Simpson predicted that PGD will become ever more popular and that within a decade the selecting and implanting of embryos that test disease-free will become the preferred mode of gene therapy.
Botkin worried that genetic testing is less regulated in this country than in many others and "may go forward without federal oversight." Of course, one reason innovations in genetic testing are advancing so rapidly in the United States is that the field has so far avoided the deadening touch of federal regulation. And even if one concedes the debatable point that there may be some role for federal oversight to insure the safety and efficacy of the tests, there is certainly no place for federal restrictions on which tests may be offered to patients. That is a decision best left to patients and their physicians.
The next session dealt with the vexed question of stem cell and cloning research. John Gearhart, the Johns Hopkins University researcher whose lab isolated human stem cells from fetal tissue in 1998, offered a quick lesson on the potential benefits of stem cells for treating human disease. He stressed that researchers are a long way from being able to offer any embryonic stem cell therapies to patients.
University of California at San Francisco bioethicist Laurie Zoloth suggested that bioethics debates are now playing the roles once played by religious controversies and political and military conflicts. She noted that every scientific body that has looked at stem cells and therapeutic cloning, including the National Academy of Sciences and the American Association for the Advancement of Science, has come out in favor of the technology. In contrast, the President's Council on Bioethics this month threw its support behind a moratorium on the research.
Analyzing the ethical debate over cloning human embryos to produce stem cells, Zoloth concluded that "we are not going to agree on the moral status of embryos, what is an appropriate family, or what is 'yucky.' " She called for mutual tolerance of differing values, but she didn't suggest how to persuade opponents to tolerate research they regard as murder.
Later in the session, Collins, the NHGRI's director, suggested that the somatic/embyronic stem cell distinction is going to get "blurry" because it will become possible to transform a skin cell into a stem cell by dosing it with the proper mixture of cytokines and proteins. In other words, researchers will no longer need human eggs to reprogram cells into stem cells. Perhaps civil war over biotechnology can be avoided as the science makes morally loaded distinctions between somatic cells and embryos less plausible.
The third session was devoted to the issue of germline gene transfer: giving patients genes that can be passed on to future generations. Gerald Schatten, a fertility specialist at the University of Pittsburgh School of Medicine, whose lab worked to produce ANDi, the first genetically engineered monkey, worried about premature federal regulation of this research. He noted that in the 1970s many people called for a ban on fertilization of human eggs outside of the body. Yet today "there are more than 1 million souls, the most beloved children in the world, who wouldn't have existed without IVF." He also argued that we have to abandon the old distinction between germ cells (eggs and sperm) and somatic (body) cells because "we can take somatic cells and clone animals from them."
Schatten suggested that assisted reproduction technology (ART) researchers should hold an ART Asilomar conference modeled after the mid-1970s conference in Asilomar, California, that set up the procedures to regulate early gene transfer research. This ART Asilomar would gather a wide variety of stakeholders to discuss how to regulate research dealing with germline transfer of genes, commerce in human eggs, embryonic stem cells, cloning, and so on. I reminded Schatten that James Watson, co-discoverer of DNA's structure, later suggested that the Asilomar regulations had delayed progress in genetic research for many years. Schatten himself noted that "ART is very innovative and is outside the purview" of federal regulations that were devised during the first Asilomar conference. He warned, "Don't put infertility patients and their doctors on one side of the fence and federal regulators and bioethicists on the other, because then we could literally end up throwing the baby out with the culture media."
Amy Patterson, director of the Office of Biotechnology Activities at the National Institutes of Health, noted that no one was suggesting any research aimed making permanent changes in the human germline because the technology is still too risky. But she was concerned that gene therapies aimed at curing diseases such as cancer in adults might be inadvertently incorporated into eggs or sperm, thus affecting their offspring. Patterson noted that some 5,000 patients have been treated with gene therapies and so far not one example of inadvertent germline transformation had been found.
Larry Goldstein, a researcher from Howard Hughes Medical Center, wondered how serious this problem is. As he reminded the participants, cancer patients who undergo chemotherapy receive high doses of chemicals known to mutate eggs and sperm, yet we don't regulate or monitor their subsequent reproduction. Michael Blaese, a former NIH researcher who carried out the first gene therapy trials in 1990, noted that one recent study had found that transposons, segments of DNA that jump around randomly in the genome, affect one in eight sperm naturally. If so, the Food and Drug Administration's concern about a one-in-100,000 chance that a gene therapy might affect sperm or eggs seems overblown. Blaese also pointed out that intentional germline interventions are unlikely to be an attractive alternative anytime soon, since most genetic disease can be prevented by means of the much less risky PGD.
The final session dealt with genetic enhancements. Lee Sweeney, a researcher at the University of Pennsylvania School of Medicine, described research in which he injects a gene that increases the expression of insulin-like growth hormone-1 (IGF-1) into the muscles of rodents. The gene becomes active only in the muscle tissue, and the subjects quickly become Arnold Schwarzenegger mice with no apparent side effects and without exercising.
Sweeney's research is aimed at helping people who suffer from muscle wasting due to aging and muscular dystrophy. He found that by adding the IGF-l gene he could prevent elderly mice from losing their muscle mass. But it would only work if he added the gene when the mouse was in middle age or younger. It couldn't restore muscle in elderly mice. He is now testing the gene in dogs, and if it works there he may try to start clinical trials in people in a couple of years.
One could imagine adding this gene to middle-aged baby boomers so they will not suffer muscle loss as the move toward their dotage. Is this genetic enhancement, or is it preventive medicine? Sweeney has already been asked to advise the anti-doping officials at the International Olympics Commission on how to detect this enhancement in future games. "The technology that allows us to treat human disease will also allow us to enhance people," he declared. Case Western Reserve University bioethicist Eric Juengst agreed. "There will always be a perfectly legitimate disease target for an intervention that can also be used for enhancement," he said.
Now to my possible complicity with suspect norms. I was assigned to the small group discussion of genetic enhancement. After a lot of wrangling, I was pleased that most of the group agreed with me that it is far too premature to suggest any regulations or legislation dealing with prospective enhancements. In fact, it might be better to allow private medical organizations to develop guidelines as the technologies mature. Interestingly, my group also agreed that research aimed at substantially extending human life spans was legitimate. If these recommendations hold up through the NHGRI process, some small victory may be won that allows research to continue without excessive government interference. So it looks like my friend is wrong; it probably is better to vote.