The dilemma of genetic testing: do we want to be "knowledge-macho"?
By STEVE BENOWITZTWO HEADLINES IN the New York Times last fall-"Breast Cancer Gene Defect Found in 1% of Jews in U.S." (Sept. 29) and "Research Links Single Gene to Almost All Breast Cancers" (Nov. 3)-heralded a revolution. The first report, in Nature Genetics, suggested a high frequency for a genetic defect among Ashkenazis, who make up some 80 percent of American Jews. The second study found mutations of the BRCA1 gene among women who had breast or ovarian cancer but no family history of the disease. BRCA1 was thought to be involved only in familial cancers, which account for just 5 percent of all breast cancers; the new finding suggested a much greater prevalence than the 1 in 300 to 800 originally predicted.
The rapid pace of discovery has pushed the still-young field of genetic testing into the public's consciousness. In the New York Times Magazine (Sept. 17, 1995), Charles Siebert, who had personally tested the testing waters, noted that "biology's pioneers are reconfiguring our futures and influencing our big life decisions."
Widespread genetic testing for diseases that occur late in life is "peeking over the horizon," says Lawrence Brody of the National Institutes of Health's National Center for Human Genome Research in Bethesda, Md. Brody, who led the Ashkenazi study, says geneticists will soon be able to paint genetic portraits, delineating risks of conditions such as heart disease, Alzheimer's disease, and diabetes. But dialing up our genetic fate will not be so simple. Most genetic tests, unlike other studies, show only a probability of acquiring a disease. Common ailments often stem from a combination of factors, frequently genes interacting with environment.
Take the putative breast cancer suppressor gene, BRCA1. Researchers at the University of Utah and at the National Institute of Environmental Health Sciences in Research Triangle Park, N.C., reported in September 1994 that they had isolated a gene that was implicated in most cases of familial breast cancer, raising the lifetime risk of women with family history of the disease to as high as 85 percent, as opposed to the normal one in nine.
Brody says BRCA1 is an example of how predictive presymptomatic testing is poised to take off. Technically, widespread testing for the BRCA1 defect associated with Ashkenazi origin is easy, because it is a single-nucleotide change. A person either does or does not have it. The greater dilemma is what to do with the information. Unlike Huntington's disease, where the mutation translates to illness, breast cancer is a matter of risk. "With the Ashkenazi finding, many women with the mutation won't get cancer," says Brody. However, not having a BRCA1 mutation is no guarantee against getting the disease. "It's still not clear what to tell them," he says. No studies have been done showing that increased mammograms, self-exams, or even prophylactic mastectomies necessarily extend lives. Brody thus doesn't foresee a huge demand for BRCA1 screening from the general population. "Without a family history of breast cancer, it's a difficult, expensive, and often ambiguous test to perform," he says.
Jeff Boyd, an ovarian cancer specialist and BRCA1 researcher at Penn, doesn't see mass genetic screenings available for most diseases anytime soon. Though commercial screening companies now test persons at high risk for certain diseases, says Boyd, most institutions lack adequate scientific expertise and psychological counseling to screen the general population.
WHILE "ALL OF these gene discoveries are steps en route to developing new treatments," notes geneticist Nancy Wexler, professor of clinical neuropsychology at the College of Physicians and Surgeons, "everyone wants to do diagnosis without knowing what the implications are. No one's sure what to do."
Wexler and others have good reason to be concerned. If a woman finds that she carries BRCA1, what does she do with the information? There's no real way to prevent breast cancer. Annual mammograms and monthly self-exams may help catch the disease early, increasing chances of a cure. But is living in constant dread of cancer really living? On the other hand, many say that knowledge allows individuals to better plan their lives.
Wexler, a leader in the identification of the Huntington's disease gene, contends that American society is "knowledge-macho." Her mother died of the disease, which strikes in middle age, eventually causing intellectual deterioration, involuntary movements, and death. Wexler prefers to keep her own decision about testing private.
"Everyone thinks that knowing anything at all is better than not knowing," says Wexler, who is president of the Hereditary Disease Foundation in Santa Monica, Calif. "But not everyone is better off." She is wary of a potential explosion in presymptomatic testing, noting that some people may be traumatized by the information. If testing were offered to the general public, it would have to include extensive counseling. "Telling someone about the breast cancer gene ... that's very scary," she says.
David Rothman, director of the Center for the Study of Society and Medicine at P&S, strongly urges giving patients choice in testing. "It is unethical to deny someone the choice of whether to be tested," Rothman says. He sees the diseases for genetic testing on a spectrum, ranging from the incurable, such as Alzheimer's and Huntington's, to the treatable, such as breast and prostate cancers. He cautions, however, that the discovery of each disease gene is certain to raise concerns over counseling, privacy of information, and the availability of medical insurance-not insignificant issues.
At the same time, test reliability is another wild card. Many scientists such as Brody and Francis Collins, who heads the National Center for Human Genome Research, suggest that testing in such cases as BRCA1 be limited to the research setting.
The National Advisory Council for Human Genome Research, which Collins chairs, and several other organizations recommend against testing for BRCA1 except in research environments.
Isidore Edelman also considers rights of patients a priority. Edelman, director of Columbia's newly expanded Genome Center, contends that families should be offered both testing and appropriate counseling. "They should have options to decide if they want to be tested," he says. He worries that insurance concerns may influence a person's choice. "These decisions should not be made by institutions." He also advocates better education about clinical genetics for both the public and physicians. "You need also to provide information on what to do, psychological support on how to cope and-always-hope."
But are genetic tests an effective preventive tool? For now, the jury remains out. In 1993, the Institute of Medicine released a report urging caution, noting that the "great commercial interest" in testing could overwhelm interests of individuals in preserving insurability and employability. Realizing the beneficial potential of tests without creating genetic pariah classes remains both a social and a scientific challenge.
STEVE BENOWITZ has written about science and medicine for a wide range of publications including Science News, the University of Chicago Magazine, the World Book Health and Medical Annual, and The Scientist, where he currently serves as senior editor. He can be reached via e-mail at email@example.com.
PHOTO CREDIT: adapted from Universal Pictures c. 1942