THE DOCTOR'S CRYSTAL BALL

By Christine Gorman

PAUL JERNBERG, A 71-YEAR-OLD mortgage banker from Chicago, walked into his doctor's office a healthy, happy man. A short while later, he left with a sense of dread. Although Jernberg felt fine, a sophisticated protein test indicated that he might have prostate cancer. A subsequent biopsy was inconclusive, but a second one disclosed that he indeed had the beginnings of a tumor. "Of course, we'll operate next week," the physician told him. Not so fast, Jernberg thought. He feared the possible side effects of prostate surgery, including incontinence and even impotence. After consulting another doctor, who explained that many prostate cancers grow extremely slowly, Jernberg decided not to have the operation. "Maybe I won't live for 20 more years," he observes. "But for me it was the right choice."

Not that long ago, doctors and patients viewed medical tests the same way military officers think about radar. By providing an early warning of a potentially deadly threat, the tests open up a critical window for averting disaster. Just because a little information is good, however, does not necessarily mean that more information is better. Physicians are starting to have at their disposal a whole new panoply of advanced tests that provide more detail about what is going on inside the human body-often down to the molecular level--than ever before possible. Yet as Jernberg discovered, such tests can warn of dangers that are so far off, they may not be worth worrying about. Knowing too much, it turns out, may prove just as harmful to your health as knowing too little.

Examples of overaggressive treatment based on test results abound in fields ranging from cardiology to back surgery. But what has brought this issue to the fore is the extraordinary pace of genetic research. In the past few months, scientists have developed experimental tests for several cancer-causing genes that were discovered only last year--including one called BCRA1, which, if mutated, can trigger breast tumors. Tests for newly identified genes that cause melanoma and colon cancer will soon be marketed to doctors.

Trouble is, the tests have been developed so rapidly that not even their creators understand exactly how much faith to put in them. Preliminary studies suggest, for example, that testing positive for the mutated BCRA1 gene does not necessarily doom a woman to breast cancer. At least 15% of the women who carry the gene will never develop the disease. Yet scientists still do not know how to tell which women fall into that category. Nor does testing negative mean that a woman can stop worrying. The BCRA1 gene appears to play a role in only 5% of the 182,000 breast cancers that develop each year. So being free of an altered BCRA1 hardly means a woman will be free of breast cancer.

Such uncertainty has prompted geneticists to proceed cautiously with testing. But if history is any guide, insurance companies and even some employers will not be so timid. In the 1970s scientists recruited black Americans to participate in a screening campaign for sickle-cell anemia, a painful blood disorder that is found mostly among people of Mediterranean and African decent. "Almost nobody foresaw the possibility that the information could be misused," says Dr. Robert Murray at Howard University in Washington. As word got out about the effort, however, some people lost jobs or were denied insurance just because they participated in the program. "The potential for harm has grown even greater today," Murray says.

Consider the case of Vickie Reis, a 42-year-old farmer who lives in Northern California. Six years ago, Reis told an emergency-room doctor treating her for bronchitis that her sister had died of cystic fibrosis, an incurable lung ailment. The physician then tested the woman and found that she bore a single copy of the CF gene. But as any first-year genetics student knows, it takes two copies of the damaged gene for a person to develop this disease. Even so, Reis' medical record subsequently contained the information about her cf gene, and she was repeatedly denied health insurance. "I had never had any symptoms of the disease," she notes. "But the fact that I carried the gene was enough to leave a big shadow on my medical history."

Even outright errors are far too common. Theresa Morelli, a healthy 32-year-old lawyer in Ohio, was refused disability insurance in 1990 because a doctor had mistakenly believed 10 years earlier that her father might be suffering from Huntington's chorea, a horribly degenerative hereditary condition that robs people of their mind and body. It turned out that he had Alzheimer's instead.

In the past three years, at least seven states have recognized the potential for discrimination. At the forefront is Wisconsin, which prohibits health insurers from requiring genetic tests and forbids employers to demand that job applicants undergo such screening. Iowa, Oregon and Rhode Island passed similar rules covering only employers. California and Ohio enacted new laws last year that prohibit compulsory genetic tests for health insurance but that still allow such requirements for disability or life insurance. "Without a law like this, you are penalized for knowing about your health history," says Dr. Paul Billings of Stanford University, who advised legislators on the California statute. "Without a law like this, there is a disincentive for being responsible for your own health."

While states press ahead with legislation, the U.S. government is issuing new interpretations of existing law. Earlier this month, the Equal Employment Opportunity Commission put out regulations stating that anyone who has inherited a genetic defect will be considered disabled. This change would allow workers, under the Americans with Disabilities Act, to sue an employer who discriminates against them because they have the wrong DNA.

But as knowledge of genetics advances, the government may be creating a legal quagmire. "Every major disorder like heart disease and cancer is partly hereditary," Billings notes. "This means that if you add up all the hereditary diseases, about 40% of the nation would be considered seriously at risk." Under the new eeoc guidelines, Billings says, 4 out of 10 Americans could legally be considered disabled even though the majority of them are healthy, show no symptoms and may never develop the expected problems.

Everyone agrees that more thought needs to be given to the questions posed by genetic testing. The federally funded National Center for Human Genome Research has organized a task force of scientists, bureaucrats, industry officials and consumer advocates, who will gather outside Baltimore next week to sort through some of the regulatory, legal and health issues. The group hopes to publish policy recommendations within a year.

In the meantime, a growing number of people, fearful of discrimination, are seeking out genetics tests without telling their personal physicians. The patients often pay for the results out of their own pocket, so they will not create a medical record that can be easily tapped by insurers or employers. The danger in this desire for privacy is that the patients will not get proper counseling on what the test result means or what their treatment options are.

Even with adequate information and advice, people can face excruciating dilemmas. Diana Lehman of Rockville, Maryland, knows she has a gene that causes colon cancer because research on her family helped scientists to identify the mutation. Anyone who bears this gene is 100% certain to develop the cancer, and while doctors are testing drug therapies, the only preventive treatment at present is surgery to remove the large intestines.

Lehman made the hard choice to have the operation, but even then she could not stop worrying. She wondered if she had passed the genetic defect on to her teenage son and daughter. "It's going to eat at you, not knowing whether your children have the gene," she says. But, she asked herself, was it fair for her to decide whether they should learn their genetic makeup? In the end, Lehman concluded, the knowledge "helps [them] to prepare for the future." The results were mixed. One child doesn't have the gene; the other has it and, unless the experimental drug treatments work, may someday face radical colon surgery.

Some people are choosing not to know their fate ahead of time, especially if there is no treatment for the ailment. Before the test for Huntington's chorea became available, a survey found that the majority of those at risk wanted to be tested. Once the opportunity arose, however, fewer than 15% took advantage of it. "When it got down to making a decision for themselves, people obviously thought about it more seriously," says Michael Watson, a medical geneticist at Washington University in St. Louis, Missouri. The anxiety of not knowing was easier to take than the certainty of horror. Those who tested positive, 10 years or more before they would develop symptoms, would lose the one thing they had left--a chance to hope for the best.

Given the ethical dilemmas as well as the scientific subtleties, many experts fear that genetic tests are being developed too quickly. "This is not something to rush into," cautions Dr. Francis Collins, head of the U.S. effort to map the entire human genome. "Your view of yourself changes [with the test results]," he notes. "You need a lot of counseling to work through this very charged situation. I'm worried that the counseling will be lost in the shuffle." Not everyone is so concerned, however. "Knowledge is a neutral thing," says Dr. David Sidransky, director of head-and-neck-cancer research at Johns Hopkins. "It all depends on how you use it. Everybody should have access to this technology."

No one denies that a better understanding is needed of what particular medical tests can and cannot do and how they should be used. "It's not the same as gazing into a crystal ball," notes philosopher Eric Juengst of Case Western Reserve University. "I've suggested that a TV weather map would be a more accurate image, not just because it comes closer to the real predictive power of these tests but also because it's not the weather forecaster's job to tell you how you'll experience the weather. He just gives you the probabilities and lets you decide what to make of them."

For now at least, it remains up to individuals to decide for themselves if they want to take a peek into their destiny. They may discover that, even with the advance of science, tomorrow is still as uncertain as it has ever been.

--Reported by J. Madeleine Nash/ Chicago, Alice Park/New York, Dick Thompson/ Washington and Tara Weingarten/Los Angeles

With reporting by J. MADELEINE NASH/CHICAGO, ALICE PARK/NEW YORK, DICK THOMPSON/WASHINGTON AND TARA WEINGARTEN/LOS ANGELES