21st: Gene blues

Why you should think twice before betting your life on genetic testing.

By Jeffrey Obser

Published March 30, 1998 8:00PM (EST)

It's time for every member of Congress, plus President Clinton and Al Gore, to go in for genetic testing. There's got to be a mutation or two that predisposes one to being a politician: an extra strand or two of particularly peppy nucleotides on the 21st century boosterism gene? A crippling gap in the sequence that codes for scientific understanding?

Two months ago, Vice President Gore put out a new proposal to keep employee genetic-test information from employers. It follows on the heels of last summer's wave of bills to keep the same information from health insurers.

"The fear of genetic discrimination is prompting Americans to avoid those genetic tests that are now available that could literally save their lives," Gore said in an address to the Genome Action Coalition, which promotes public support of genetic research.

Now, opposition to genetic discrimination is an easy political flag to wave, and frustrating the work of health-insurance bureaucrats is always a crowd-pleaser. But Gore's enthusiasm for genetic testing betrays the other motive in Washington for "genetic discrimination" laws: a blind belief in the manifold benefits genetic testing can confer. From this perspective, anything that prevents Americans from lining up to get genetically tested, to consume the as-yet-unproven biomedical products of our rush to decipher the human genome, is unconscionable -- deadly, even.

Which is nonsense. In fact, in these early days of genetic testing, a blood report that says you're at unknown risk of getting an incurable disease at an unknown time is as likely to take the hope and joy out of your life as to "save" it.

Admittedly, people have already lost health insurance or jobs because tests have shown they have "bad" genes. Legislation to keep the information private might not be a bad idea. But there's an even better reason to protect people from discrimination based on genetic test results: The "information" itself is often so vague as to be worthless.

If a genetic test shows you have a dangerous genetic mutation, you'll only know that you may get the disease, or maybe not -- and you won't know when. Until a test has been put through years of studies, the risk estimate it offers will typically be based on studies of small populations that took the test right after its release. And these particular groups are often more likely than most to have the disease, regardless of their genes -- that's why they're in the study in the first place.

A perfect illustration is "the" breast cancer gene, BRCA-1. The first year after it was identified in 1994, women with a certain mutation to that gene were told they had an 85 percent chance of getting cancer. But within a year, new studies lowered that to 50 percent. Last May, a study came out in the New England Journal of Medicine with a 16 percent figure. Finally, last week, two more studies came out in the Journal of the American Medical Association saying that the BRCA-1 mutation is so rare that it's "premature" for most women to take the test at all.

Many women with family histories of breast cancer leapt at BRCA-1 testing, thinking it a miraculous gaze into a crystal ball. For those confronting the terrible decision whether to remove their breasts, the test seemed to offer an extra bit of helpful evidence. But as time went on, the BRCA-1 test turned out to be less like a crystal ball and more like a weather report.

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Like the weather, a gene mutation expresses itself depending on unpredictable, uncontrollable things -- environment, daily lives, the presence of other genes, all of the above, two out of three. That's why all of our genes that have complicated relationships to disease, as well as personality and behavior, will speak to us like weathermen. We'll know the genes, like the clouds, are there. We'll know they're probably storm cloud genes or just light-sprinkle genes. But we're many years from using genetic information to make solid predictions or tough medical decisions with any certainty.

To understand why genes will cling tenaciously to their unfathomably complex secrets, it helps to understand how scientists link them to specific traits. Naturally they don't get to watch a gene in action as it fails to produce the enzyme that unclogs the lungs of a child with cystic fibrosis. Instead, they go after genes the way special prosecutors go after politicians: from afar, piecing together evidence that connects the gene to its effect. It's easier to trace a gene that has an obvious effect on lots of people, for the same reason that serial offenders are easier to convict in court -- because their modus operandi is the same throughout many crimes.

Science has long since identified genes for diseases with clear genetic roots like Huntington's, but it stumbles over genes with murkier roles in illness. It may be feasible to study 1,000 married, nonsmoking Jewish men with family histories of colon cancer to see which gene they might have in common. But cancer, like diabetes, heart disease, Alzheimer's and most other common diseases, is only partly caused by genes -- and then, often by 10 or more genes working in concert. So once all those genes have been staked out and the statisticians have read the nonsmoking Jewish men's DNA prints, they'll have to follow them around for 20 years and see who got the illness, when and from which of the five or 10 suspect genes.

Even then, the statistics will still be pretty shaky -- researchers will never get all those men to follow similar diets or be exposed to the same environmental toxins. This is why most genetic tests will never give much more than vague indications of susceptibility: The gene may be discrete and locatable, but the number of variables acting on it, and on one another, pushes an individual's possibilities off into unchartable complexity. Would a police detective spend quite so much time looking for the smoking gun if he knew it had 1,000 different fingerprints on it?

In spite of all this, biomedical companies are apparently pushing doctors to prescribe tests to patients before anyone has any idea how accurate they are, fueling unnecessary treatments, stress and family tensions. They're getting help from the National Institutes of Health, which has been pushing to have all pregnant women offered a genetic test for cystic fibrosis -- a test that is only 70 percent conclusive for Caucasians and 30 percent for Asians, with Hispanics and African-Americans in between. Many health professionals resent government pressure to offer dubious, and costly, genetic tests. Yet more such population-screening pushes are on the way.

The NIH is trying to establish the cystic fibrosis test as "standard of care," meaning it's commonly accepted medical practice. Once that happens,
doctors have a legal incentive to err on the side of more genetic testing, rather than less. "Wrongful birth" suits are already being launched by new parents furious that a genetic test referral might have spared them from having to raise a child with a birth defect.

"The companies push like mad because they want to make money, and they insinuate to the doctors that it'll be malpractice if they don't give these tests," says Nancy Wexler, a Columbia University professor who heads the Hereditary Disease Foundation and led the effort to isolate the gene for Huntington's disease. "The physicians are trying to figure out when a test is ready for prime time, and a lot of the companies don't care."

Were biomedical companies to go searching for "the" gene that keeps you healthy, or sane, or long-lived, they'd never sell the test to anyone. This is why genetic testing promises only bad news: Healthy people don't need explanations; sick people, however, are a recession-proof market.

Commercial pressure to implement genetic testing flourishes in today's media climate. Careers are being made convincing the public that in a very few years we'll all carry around scanning cards with our genetic future mapped out in magnetic bits. Book contracts are flying in all directions to scientists and bioethicists who indulge in speculative moralizing about supposed genetic possibilities. With "Gattaca," even Hollywood has carved out a stake in the gene myth.

They're catering to a popular concept of genes-as-destiny that stretches way back in our culture -- Shakespeare's plays are filled with blood-as-fate references, and Oliver Twist, child of nobles raised among orphans, instinctively knows how to use the subjunctive even though he's never heard it in his life. Our own hot pursuit of genetic-health predictors comes at a time of increasing comfort with scientific justifications for growing chasms between class divisions, and of shrill political hostility to the "liberal" notion that behavior and destiny are partly a product of the environment.

But if we seek answers in genetic testing, we'll merely be escorted to the hazy, ever-shifting border between nature and nurture -- a territory full of statistical black holes where no study can squeeze the complexities and variety of human lifestyles into definitive and reliable "facts" about what genes really do. Most genetics researchers will tell you all that if you just ask them -- especially if they're not trying to sell gee-whiz books about a wondrous future of cloning and designer personalities.

The truth is that relatively few of our genes are ever going to give us a clear indication of our "fate." One geneticist told me point-blank, " It's how we live our lives that determines what our risks really are."

The real long-term value of all this genetic research will be to uncover the biochemical pathways by which things go wrong in the body, so that treatments, genetic and otherwise, can be perfected. But that, geneticists say, is many years down the road. Considering that every single human being carries seven mutations that make them susceptible to fatal diseases -- or 30, or 100, depending on who's talking -- people should ask whether there is any point in identifying these mutations before treatments are available to prevent or cure the disease.

Unfortunately, the world of managed care has increasingly viewed genetic counselors, the folks who ask you if you really want or need a test, as a luxury. The master's degree programs that provide this unique combination of family psychology and molecular biology suffer from a dearth of jobs for their graduates. One hears a nationwide sigh of resignation that there will never be enough genetic counselors -- from federal health agencies, the health-care system and even most academic "bioethicists" who get grants from the Human Genome Project's generous ethics budget to mind social policy on genetics. This, at a time when more and more patients have to make life-changing decisions based on vague clinical risk estimates, even if their knowledge of math goes no further than balancing a checkbook.

"Americans are terrible with probability theory," says Boston University bioethicist George Annas. "That's why Las Vegas does so well."

Instead, genetic counseling is to be turned over to doctors, nurses, Internet sites, interactive computer programs and -- how's this for objective health information? -- toll-free numbers set up by companies that offer genetic tests.

Considering the average doctor's visit lasts seven minutes, computer programs and Internet sites might be more practical and thorough. But at a Stanford University conference on expanding genetic testing for Alzheimer's last October, Henry Greeley, co-director of the university's genetic-ethics program, noted, "Humans don't perceive risk the way computers would like them to." Even the most levelheaded, he said, often suffer emotional breakdowns when they get scary test results.

At the same conference, Dr. Paul Berg, a Stanford professor in cancer research, called the genetics community's intentions to educate the broad public about testing issues "pie in the sky."

"If you make the case that your genes are telling you something," Berg said, "you need to have someone telling you that in a way that is personal. The question is this: Is the health-care system going to pay for this thing? Perhaps, but it's not on the horizon."

That's why we need to genetically test all the politicians as soon as possible. If we could screen them better for the 21st century boosterism gene, we might end up with leaders who are less infatuated with biomedical science. Maybe then they'd take a more sober look at its impact on real people -- who encounter it far from the droning rhetoric of progress and economic growth, in little white rooms, by the ticking of a clock.

Jeffrey Obser

Jeffrey Obser is a freelance journalist who has also written about genetics issues for Newsday.

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