Keeping Your Genes to Yourself

Genomic research promises to provide a new understanding of disease, new cures for ancient scourges, and individualized therapies, tailored to a person's genetic makeup. But your genes could tell employers, insurance companies, and the government more about you than you want them to know. Now, lawmakers and ethicists are trying to figure out how to preserve your genetic privacy. So many big government programs have spawned such damaging side effects over the past few decades that Washington cynics have coined a term for the phenomenon: the Law of Unintended Consequences. When Nobel Prize winner James Watson became head of the Human Genome Project in 1989, he tried to defend against such unforeseen difficulties by devoting 3%--and later, 5%--of his $3 billion budget to studying the ethical, legal, and social implications of genome research, an effort that became known by the acronym ELSI. His plan might be working. Scientists declared the human genome sequence "complete" in April, and already lawmaking bodies and the public are wrestling with the societal implications of that accomplishment. Such ethical considerations include how much information--if any--should be available to insurance and health organizations; whether insurance companies will be permitted to ask for blood tests before granting coverage; and how we can safeguard against genetic discrimination in employment and insurance. This month, a panel of experts on health insurance and policy will explore these issues in a SAGE Crossroads discussion, "Decoding the Genome, Genetic Predisposition to Disease, and Health Insurance: What Do We Know and Who Do We Share It With?" Questions Remain The "complete" human sequence--an ordered list of the 3 billion chemical letters in human DNA--represents about 99% of the gene-bearing regions to an accuracy of 99.99%, which is the best that current technology can do, according to the National Human Genome Research Institute (NHGRI) in Bethesda, Maryland. Having the sequence could allow researchers to identify disease-causing genes more quickly, develop gene-based therapies for the treatment of human diseases, and better understand the genetic and molecular basis of health and longevity. But we're not there yet. Scientists believe that the human genome contains about 30,000 genes, but they still don't know what most of these genes do. And knowing how genes function is key to understanding how they collaborate to form a healthy human being or how they malfunction to cause disease. "We haven't decoded the genome by any stretch," says Robert Nussbaum, chief of the genetic research disease branch and the inherited research disease branch at NHGRI. "We've only just started to get who all the players are." Even recognizing the players is a challenge. "Some of what you think are genes may be false positives, and not real genes at all," says Nussbaum. "And there may be some genes hidden in there that you're not smart enough to know how to find." Nevertheless, by the beginning of this year, researchers had identified nearly 1500 genes that can cause or predispose a person to disease if he or she inherits a damaged form. And to date, scientists have developed more than 900 laboratory tests to detect these defects. Almost half of these diagnostic tests are already available clinically. The discovery of disease genes and the development of these diagnostic tests have stirred a rising fear of genetic discrimination. A series of nationwide surveys in the 1990s turned up several hundred cases in which health insurance companies had denied people coverage because of adverse genetic information, and in a 1995 Harris poll, 85% of the people contacted said that they feared that insurance companies would use genetic test results against them. Legal Privacy Zones State lawmakers were the first to respond to these anxieties. Wisconsin outlawed genetic discrimination in 1991, and more than 40 states now have genetic discrimination or privacy laws on the books. In 1996, Congress followed suit. While considering a bill designed to protect employees' rights to group health insurance, legislators inserted a provision barring insurance companies from excluding any individual--or charging that person a higher rate--because of genetic information. In February 2000, then-President Bill Clinton issued an executive order outlawing genetic discrimination in federal employment. And on 23 June 2001, President George W. Bush called for broad legislation to make genetic discrimination illegal. "To deny employment or insurance to a healthy person based only on a predisposition violates our country's belief in equal treatment and individual merit," Bush said in his Saturday radio address. To that end, Congress is now moving to broaden the 1996 anti-discrimination provision. On 21 May, the Senate Committee on Health, Education, Labor, and Pensions unanimously approved a long-sought measure that would prohibit genetic discrimination in both health insurance and employment. The 82-page bill, dubbed the Genetic Information and Nondiscrimination Act of 2003, bars insurance companies from ordering genetic tests or using genetic information to deny coverage or raise premiums. Unlike the 1996 Health Insurance Portability and Accountability Act (HIPAA), the new bill applies to individual as well as group health insurance plans. Under the bill, people who are denied health insurance because of genetic information--that is, data from their own genetic tests, from tests of family members, or information about a genetic disease in their family--could go to court to get coverage restored and their medical expenses reimbursed. They also could collect penalty payments of $100 a day, although they would not be allowed to sue for unlimited damages. The bill would also prevent employers, labor unions, and employment agencies from ordering genetic tests or factoring genetic information into decisions to hire, fire, transfer, or promote. Violations could lead to hefty back pay and penalty awards. No one knows how widespread such employment discrimination might be. However, a 1998 report by the U.S. Equal Employment Opportunity Commission (EEOC) and the Departments of Labor, Justice, and Health and Human Services recorded several anecdotal cases of people being turned down for jobs or fired because of genetic conditions that wouldn't compromise their health or their capacity to work. Under a different law, the Americans with Disabilities Act (ADA), EEOC has already waged one genetic discrimination case. In 2001, the commission accused the Burlington Northern and Santa Fe Railway Co. of violating ADA by trying to force 36 workers who complained of carpal tunnel syndrome to be tested for a preexisting genetic condition. Last year, the railway settled the case for $2.2 million--which was to be divided among the workers who filed the complaint. Critical Praise The Senate committee's unanimous approval of the new bill is "an enormous accomplishment," says Kathy Hudson, director of the Genetics & Public Policy Center in Washington, D.C., an arm of Johns Hopkins University. "The specific prohibitions in the bill are exactly appropriate," she says. Judith Lichtman, president of the National Partnership for Women & Families, also praised the bill as a major step forward but called for "more meaningful enforcement provisions." She argues that companies that misuse genetic information should face higher fines as well as lawsuits--with no ceilings on damages. The measure has strong bipartisan backing and seems certain to win quick Senate passage. "We have an obligation, a responsibility, to protect people from the threat that their genetic information can be used against them," said Republican floor leader Bill Frist (R-TN) to the Senate on May 23. "I would say that, from a medical standpoint and from a societal standpoint, this is a moral responsibility." But prospects in the House are less certain. Several House committees can claim jurisdiction--lengthening the obstacle course that the bill must navigate--and the measure will face continued industry opposition. The U.S. Chamber of Commerce, a body that represents mostly small companies and has considerable clout in the House, contends that evidence of genetic discrimination doesn't exist and also considers the bill's penalty provisions too strict. Donald Young, president of the Health Insurance Association of America, derides the bill as "a solution in search of a problem." Now for the Hard Part However controversial the current bill may be, the problems it addresses are probably the most straightforward--and thus easiest to resolve--of the dilemmas that genome research will pose. The ELSI program is now exploring many of these more tangled ethical conundrums, and it has funded the graduate school training of a generation of bioethicists to argue about them. So far, no consensus has emerged. For example, the question of whether life insurance companies should also be barred from looking at genetic data seems too hot to handle. People might have a societal right to health insurance, the industry argument runs, because it is essential for receiving medical care. But life insurance is optional. Moreover, if someone seeking life insurance has a genetic condition that could lead to an early death and knows it, he or she has an unfair advantage over the insurance company. "It would not be reasonable to have a complete prohibition on life insurers having genetic information that the insured has," agrees Hudson. "On the other hand, a life insurer should not make somebody have a battery of genetic tests in order to determine whether or not they are insurable." Whether life insurance companies would make much use of genetic data, as it exists today, is another question. Most current genetic tests can indicate only that an individual has an increased risk of developing a particular disease. But predisposition is not destiny. What's more, most genetic diseases develop before people hit adulthood--and start shopping for life insurance. "The people who are actually encountering problems with insurers are people who have a disease, not people who have a predisposition to a disease," says William Nowlan, chief medical officer of the National Life Insurance Co. in Montpelier, Vermont. Another question that is raised frequently--and never answered--is whether genetic tests should be made available to the public when no therapy exists for the condition they might reveal. In the 1990s, tests for alterations in the breast cancer genes BRCA1 and BRCA2 that signify a predisposition to the disease were on the market long before physicians could tell women what to do if they tested positive. A particular version of the apolipoprotein E gene, APOE4, signals an unusually high risk of developing Alzheimer's disease. But no one has figured out how to stave off the disease, and many people with that form of the gene never develop Alzheimer's. Patients can get tested today for the genetic perturbation that causes Huntington's disease. But a positive result is a sentence to mental deterioration and death; there is no cure. So the question remains whether such tests should be prohibited or whether people have the right to decide for themselves whether they want to know. "One of the areas that genetic counselors are very interested in is the effect on one's psychological well-being of knowing that one is carrying a certain predisposition--or knowing that one has escaped from a predisposition that others in the family have," says NHGRI's Nussbaum. No good answers have arisen. Reproductive genetic testing raises closely related questions (see the SAGE Crossroads debate, "Do we want science to redesign human aging?"). Genetic testing of embryos generated by in vitro fertilization can detect a predisposition for Huntington's disease or other disorders before the embryos are implanted. Amniocentesis is often performed on pregnant women in their mid- to late 30s to detect Down syndrome in the fetus, and women frequently are offered a test for cystic fibrosis (CF) at the same time. But people with CF now have a life expectancy of about 32, and improved treatments probably will extend that. Many people wonder whether CF should still be considered a life-threatening disease that justifies terminating a pregnancy. Hudson also worries that data on genetic variations--small differences in DNA sequences that occur within human subpopulations--might be misinterpreted, fomenting new misconceptions and new tensions among racial and ethnic groups. So far, this scenario hasn't materialized. If anything, genetic analyses have found that racial differences don't exist. In attempting to anticipate the possible ramifications of genomic research, NHGRI's ELSI program has cast a wide net, exploring issues ranging from the impact of patents on genetic research to the implications of genomics for theology. But only a foolhardy observer would predict that other, unanticipated questions won't arise. By definition, unintended consequences are unforeseen. Bruce Agnew is a writer in Bethesda, Maryland. Sad to say, he's a big believer in the Law of Unintended Consequences.