Scientists Struggling With Concerns Raised By Genome Project Progress

Genome Project Progress Some firms and institutions are establishing ethics branches to focus on policy issues left unresolved by NIH's ELSI project. RULES REQUIRED: Stanford's Paul Billings thinks ELSI has fallen short in creating a "regulatory arena". Many scientists are finding that concerns about the complex ethical, legal, and social issues surrounding genetic testing and the use of the resulting information are taking up a larger part of their time. In response to this shift in focus, and taking the conceptual lead from the Ethical, Legal, and Social Implications (ELSI) branch of the Human Genome Project (HGP), a growing number of biomedical institutions are organizing in-house committees and task forces to examine various ethical issues related to genetic testing and gene therapy. They are tackling a range of questions, from issues of genetic discrimination in jobs and insurance to informed consent, patients' right to know, rights to stored DNA and tissue samples, and access to genetic information. But their effectiveness may be in question, given that ELSI's own success, and even its very mission, have been controversial. Supporters contend that HGP's ELSI program, now entering its sixth year, is adequately performing its role of bringing to scientists' and society's attention ethical issues involving genetic testing and discrimination and other related matters. Critics, on the other hand, argue that ELSI has been ineffective and is not a player in public-policy discussions. Complicating matters is the fact that earlier this year, Lori Andrews, a professor of law at the Illinois Institute of Technology's Chicago-Kent College of Law, resigned as chairwoman of the ELSI working group. The working group was set up to advise ELSI, Congress, the president, and the public on the implications of the HGP, though it is funded separately from the money set aside to support ELSI. Mark Rothstein, a professor of law at the University of Houston, is cochairman of a National Institutes of Health task force to evaluate the effectiveness of ELSI's advisory working group. To date, it has met only once. Andrews did not return repeated phone calls from The Scientist. The new focus on ethics, some say, is in response to more attention to these matters on the part of both the public and scientists. "There is an increasing concern on the part of the public regarding future discrimination based on genetic testing," says geneticist David Page of the Whitehead Institute for Biomedical Research in Cambridge, Mass. "There is a perception [among researchers] that scientists are confronting these issues, especially those who are dealing with patients and families, and they need to be trained," adds religion professor Ronald M. Green, director of the Ethics Institute at Dartmouth College. Green is also director of the Office of Genome Ethics at NIH's National Center for Human Genome Research (NCHGR). The Whitehead Institute is one of several organizations that are reaching out to the public. Two years ago, it established the Whitehead Task Force on Genetic Testing, Privacy, and Public Policy, a joint venture with the Shriver Center for Mental Retardation and Harvard University's Kennedy School of Government. The task force is a grass-roots effort organized to increase public understanding of the issues surrounding gene testing, as well as to stimulate discussion of potential legislation. Other organizations, such as NCHGR, which established ELSI in 1989, are concentrating on educating their own staff who are involved in clinical genetic testing, in addition to planning protocols. Industry has gotten into the act as well. Biotechnology firms are paying increasing attention to ethical issues surrounding genes and genetic testing. The Institute for Genomic Research (TIGR), a nonprofit organization in Rockville, Md.; SmithKline Beecham plc, headquartered in London; Genzyme Genetics in Framingham, Mass.; and Millennium Pharmaceuticals of Cambridge, Mass., are just a few involved in establishing in-house ethics committees. According to Rothstein, several universities that have NIH-funded human genome centers also have so-called ELSI centers to examine various ethical aspects of their work. The University of Iowa in Iowa City, for example, is looking at issues surrounding stored tissue samples and informed consent. Other schools with such centers include the University of Utah and Stanford University. The task of identifying the approximately 100,000 human genes is daunting indeed. Perhaps more baffling, however, are the topics that ELSI was created to confront: the growing legal, ethical, and social dilemmas resulting from the new scientific knowledge. For example, can an insurance company deny health coverage to an individual with an underlying genetic predisposition to colon or breast cancer? The NIH branch of ELSI (there is a Department of Energy version that focuses on privacy issues and public education) in some ways is still regarded as an experiment. Its mission is to support scholarly studies and develop issues for discussion. However, many scientists and ethicists observe, this role has been evolving toward policy design-though ELSI carries no formal policy-making authority. Some say it must formulate policy to remain relevant. When NCHGR started the branch, it received much praise from scientists as well as ethicists for its foresight in predicting what issues would be important. But has it lived up to its initial promise? In an analysis (Five Year Review of the Ethical Legal, and Social Implications Research Program, April 12, 1996), interim chief Elizabeth Thomson paints a rosy picture of its performance, citing an impressive list of reports and studies. In an article in the Los Angeles Times (L. Garrett, March 3, 1996, pages 23-50), science writer Laurie Garrett calls ELSI unprecedented because it's aimed at exploring a scientific revolution even before it began. Indeed, at ELSI's inception, the HGP was just getting off the ground. Thomson notes that ELSI, which has spent some $26 million funding studies over the past five years, has seen some bumps along the way. However, she considers its studies and various task-force and working-group reports as part of its success. Critics suggest otherwise. Many argue that while ELSI is adequate for funding scholarly studies, its job is not to reach scientists with advice, but to stir discussion and foster public-policy debates. And that, they say, isn't enough. Its most recent effort was a March resolution, "Interim Principles of the Task Force on Genetic Testing," drafted by ELSI's Task Force on Genetic Testing. The document addresses various issues related to genetic testing, such as access, confidentiality, and privacy. WHO'S THE BOSS? Case Western's Thomas Murray points out that ELSI lacked authority to make policy. "There's always been some controversy [over] whether ELSI should have taken more of a public-policy stance," suggests Thomas Murray, director of the Case Western Reserve Center for Biomedical Ethics, and a member of the original ELSI advisory working group. Murray chaired the 1993 ELSI task force on health insurance. He believes the report has played a role in the enactment of state laws on health insurance portability and restricting discrimination based on genetic-disease susceptibility. However, "even the insurance task force report isn't a policy statement, but a background document clarifying the issues. We make recommendations, but they are not detailed prescriptions for health-care reform," Murray says. Murray asserts that the task force lacked the political authority to develop policy recommendations. "First, were we properly situated to make policy? Look at the task force-we were an ad hoc task force of a working group of an advisory committee of a center of NIH. . . . We were not a group that had the authority to dictate national policy. We didn't have the resources to do a national study. "We saw our role as sorting out the issues relevant to policy to make them accessible to the public and policy-makers and immediately inform them of choices," Murray continues. "We were more comfortable one step removed from policy-making. "One of the big tensions has been, should the ELSI program be responsive to public policy and the larger political community, or responsive to the scientific community? Should it make policy, or just encourage others to make policy?" TREND-SETTER: Case Western's Eric Juengst considers the ELSI "experiment" a success, on the whole. ELSI has "had successes and failures," says Eric Juengst, ELSI's first director and now associate professor of biomedical ethics at Case Western Reserve University Medical School. "On the whole, ELSI has proven itself. Still, it has a long way to go before we see what becomes of the work it has produced." Juengst considers the increased institutional and corporate attention to ethical and social issues "a testimony to the ELSI experiment." WORTHWHILE: Johns Hopkins Gloria Petersen notes that some scientists doubted the value of ELSI studies. Cancer epidemiologist Gloria Petersen of Johns Hopkins University School of Hygiene and Public Health believes that ELSI efforts have been worthwhile. However, she notes that when ELSI was established, "many scientists were not happy that bench scientists received funding for social studies," taking away money from their own scientific projects. Funded investigations, for example, included examinations of various ethical concerns related to cystic fibrosis screening, as well as issues surrounding the HGP and access to health care. "These are unprecedented studies," she notes. Yet, "early on they were funding [mainly] social scientists and philosophers, and these did not endear ELSI to the scientists." Petersen applauds the foresight of those who created the ELSI program. "It was an extremely wise thing to put money into these [ethical and social] issues because, as you can see from the [disease gene discoveries and genetic testing] developments that occurred, there are enormous [ethical, social, and financial] implications" from the discovery of genes for Alzheimer's disease, breast and colon cancer, and other disorders. "And there will be more," she predicts. "It was very wise to look at these in an unbiased manner. These [studies] will be of tremendous benefit when we get into complex disease research." Paul Billings, acting associate professor of general internal medicine at Stanford University and an early ELSI working group member, notes that many scientists hoped ELSI "would provide restraint on the development of certain fields, and that ELSI would create the regulatory arena to control the marketing of certain tests that might be used in [job and insurance] discrimination, such as breast-cancer predisposition, though it has yet to do so." Billings argues that ELSI needs to be broader. "Its original intent was to develop a diverse range of views while commenting, doing research, and writing books and articles to influence how genetic testing was publicly received. Its other job was to establish an advisory group to create public policy that could be enacted politically. It's lacked leadership in both those roles." IN EVERY POT: Arizona's Benjamin Wilfond thinks an ELSI program should exist at each NIH institute. Some scientists, such as Benjamin Wilfond, an assistant professor of pediatrics at the University of Arizona, contend that there should be the equivalent of an ELSI program in every NIH institute. "Some people think ELSI should be similar to other parts of NIH by doing research and not considering formally the consequences," he notes. "I think ELSI has done as good a job as it could have done. The task force for genetic testing is a move in the right direction, bringing together the scientists from academe and industry. The next step is to implement the recommendations into policy. The question is, how much responsibility should ELSI have? It's been criticized for having too big a role. It's learned it can't be a policy-maker, but more of a facilitator." Jeff Botkin, director of the University of Utah's human genome center's Genetic Science in Society program, notes that a report from the National Academy of Sciences last year (Society's Choices: Social and Ethical Decision Making in Biomedicine, Washington, D.C., National Academy Press, 1995) concluded that a comparable ELSI program should be established in each NIH institute. Botkin, an associate professor of pediatrics and biomedical ethics, contends that part of the criticism of ELSI, which he views as unwarranted, involves the proper role of the working group. Should it provide guidance to ELSI's extramural grant program, or should it be a policy-making group? Botkin argues that ELSI was never set up to create policy. It has, however, "helped spawn university and corporate programs partly by raising the profile of the issues in general and by helping foster expertise from which companies can draw." While scientists and administrators continue to discuss and perhaps redefine ELSI's purpose, other institutions are getting into the act. Whereas ELSI lacks a policy-making directive, many academic institutions and companies are creating their own ethics committees to both discuss and set policy for their organizations. Philip Reilly, executive director of the Shriver Center for Mental Retardation, is a member of a special group of scientists and legislators who are examining these issues in a unique setting. At the Whitehead Institute, geneticists Reilly, Page, and their colleagues are members of the two-year-old Task Force on Genetic Testing, Privacy and Public Policy. REACHING OUT: Whitehead's David Page believes more education efforts are needed. "We were asked by legislators what would we do as scientists to help the public understand the potential ethical, legal, and social consequences of the Human Genome Project," explains task force chairman Page, who is also associate director of the Whitehead/MIT Center for Genome Research. David Page, Whitehead Institute for Biomedical Research: "There's a slew of public-policy questions to consider. Genetic information is powerful, and the citizenry is concerned about its use." Reilly is impressed by the group, and notes its different role from ELSI's. "On three or four occasions, we've met with legislators and talked about issues in genetics. To my knowledge, ELSI has not done that." "I think it benefits the scientific community to be that close to government," he says. "How should public policy on the question of genetic testing be formed? We tried to take our view outside of our educational institutions and put it in the public view. We found that many of the uses of genetic information fell under state jurisdiction." While the task force's mission is education, it has also attempted to foster public-policy debate, he adds. The task force has continued to schedule briefings with legislators, the attorney general, judges, and other decision-makers. Says Page: "There's a slew of public-policy questions to consider. Genetic information is powerful, and the citizenry is concerned about its use. "Some concerns are about access-who owns genetic information and who controls access, such as employers, insurers, and relatives. "Beyond this are scientific and technical questions. Who should ensure the quality of testing? Now it's done in specialized testing centers. It's not yet in the physician's office, but it may move there soon." Page thinks other publicly funded institutions should follow the MIT lead. In this case, he contends, ELSI is insufficient; there should be more grass-roots efforts. He adds that scientists themselves can learn about these ethical issues by bringing these topics to public discussion. Reilly maintains that medicine lags behind in technology transfer. "We've devoted a lot of time considering the effects of genetic therapy, for example, but haven't considered how to translate the fruits of the genetic testing to the physician and clinical medicine," he points out. Corporate Initiatives For that reason, Reilly is impressed that some biotechnology companies are examining such issues internally. "I've seen Myriad Genetics talk about the right ways to deal with situations," he says. About a year or so ago, SmithKline Beecham created a Public Policy and Bioethics Advisory Board, which he chairs. Meeting three times a year for two days, the board, composed of scientists, lawyers, and ethicists, discusses issues such as genetic privacy, insurance, and access to information. "It's certainly new," he says about biotechnology company activity. "Based on what I've seen, there's definitely an increase in this sort of activity. Companies are putting resources into it." In October, SmithKline Beecham awarded Stanford University $950,000 over three years to create a program to study the social, ethical, legal, and political implications of human genetics. Yet not everyone is ready to call the activity a trend. Cancer epidemiologist Gloria Petersen isn't so sure there's is a widespread effort as yet. It may be too early in the game, she contends, for some biotechnology companies to form special bioethics committees to deal with genetic testing and information issues. Petersen is on the internal review board of a local biotech company. But she contends that of four gene-testing companies, only one has a review board that is looking at the impact on those being tested, though each firm likely has some sort of advisory board. She thinks that some companies may not see it as their mission to deal with counseling patients, but she doesn't think they necessarily ignore their patients' concerns. "I don't think it's in their mission to take up grass-roots efforts in this regard," she says. Glenn Miller, head of the clinical trial laboratory at Genzyme Genetics, says his company has one of the largest genetic counseling support networks in the United States, for both patients and physicians. "We're trying to participate in the continuing education of physicians to allow them to do as much as they can themselves," he states. Miller explains that a counselor would step in when the physician or testing clinic "isn't comfortable with dealing with probabilities and the genetics involved." Genzyme has the largest prenatal molecular genetics laboratory in the U.S., he claims, and the largest number of tests are for cystic fibrosis gene mutations. The company also tests for fragile X syndrome. "As the number of genes increase, the number of companies testing for them increases as well. The industry has been mostly responsible in dealing with reporting test results." Miller observes that modern genetics involves probability, which is something very new to physicians. "Testing, as well as how you communicate that risk to patients, demands much more thought. It's important to evaluate these tests in carefully controlled studies." CORPORATE CONSCIENCE: Steven Holtman of Millennium Pharmaceuticals notes his company's attention to bioethics training. Though Millennium Pharmaceuticals doesn't offer genetic testing, the company has a staff ethics adviser and runs an eight-week, in-house bioethics course, according to chief business officer Steven Holtzman. "We have an enlightened program making sure people understand the kinds of genetics research we're doing." Holtzman also cochairs a bioethics advisory committee for the Washington, D.C.-based Biotechnology Industry Organization. "We have the industry organization committed to the fact that understanding bioethical issues, including the socially responsible use and as well as abuse of genetic information, is important to its future." 'Toxic Knowledge' Whatever the future of ELSI or its working group, the issues they discuss will not go away soon. FUTURISTIC: Darmouth's Ronald Green says genetic medicine involves "families and prospective generations." In May, at the annual meeting of the American Society of Clinical Oncology in Philadelphia, Reilly asked the audience of mostly cancer physicians and scientists: "What do you want to know regarding your genetic heritage and your potential genetic future? And then, who do you want to know this information? Your insurance company? Your employer? What about your family?" There are tests today for any number of disorders, such as Huntington's disease, cystic fibrosis, and colon and breast cancer, for example. New disease genes are being uncovered for epilepsy, diabetes, Alzheimer's-the list goes on. By some estimates, they are increasing at a rate of one new disease gene a week. Page thinks that medicine will continue to be in an "uncomfortable zone, in which we can diagnose but not treat. The genetic information in this window is sometimes referred to as 'toxic knowledge.' "In many cases, the predictive value of the tests [is] uncertain," he observes. "Take BRCA1," he says, referring to the first breast cancer susceptibility gene, discovered in late 1994. "Scientists don't know what to say about [using the gene for] prognosis and prediction of breast cancer-they are at best probabilities. "The other issue is what to do with the information in the absence of therapy." Reilly says that genetic medicine will likely change the way medicine is done in the next two decades. "It opens up the possibility of predictive medicine where we can intervene before disease occurs," he observes. He cautions that "the big dilemma in genetic medicine is that we'll have diagnosis and risk information before therapeutic intervention. That poses a lot of problems." Dartmouth's Ronald Green agrees. He contends that genetics has changed the way doctors perceive disease and medicine. "We're talking about a predisposition years ahead of actual disease. Our social systems aren't used to handling it. "Another issue is the familial nature of genetic medicine. We can't think of medicine as the ill person and the doctor; it's being shattered. It's not the individual, but families and prospective generations."

Scientists Struggling With Concerns Raised By Genome Project Progress

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