Paula Wishart, a career counselor from Ann Arbor, Michigan, learned in her 40s a sinister family secret: Lynch syndrome runs through their genes.
Lynch syndrome is caused by a collection of genetic mutations that vastly predispose a person to an early and aggressive form of colon cancer. (In women it's linked, too, with uterine or endometrial cancer.) The mutations were discovered in the early 1990s. That was too late for a whole string of Wishart's ancestors—including her great-grandfather and her grandfather. Their mysterious deaths fostered the mythology that there was, as Wishart puts it, "bad blood in the family."
Lynch syndrome is like an assassin hiding in the attic with a dozen different ways to kill you. It's a specter so dire that, when Wishart's aunt learned a decade ago that there were now tests for diseases like Lynch, "she wanted no part of it," Wishart recalls. "The feeling was, 'Why would I want to know that?'" That aunt died of colon cancer. Shortly thereafter, her daughter—Wishart's beloved first cousin—succumbed to cancer in her 40s. "If my aunt had been screened, then my cousin would have been screened earlier," Wishart says. "It could have prevented their deaths."
Wishart's aunt's choice to remain in the dark was by no means unusual. Genetic screening for a potentially fatal illness is so fraught and frightening that most candidates for such a disease don't get tested.
Wishart, too, had been scared to know. But she was more scared not to know. When her mother's tissue sample tested positive for Lynch syndrome, she and her four siblings were tested. Her three older siblings came out clear. Wishart and her twin brother weren't so lucky.
She had a mutation in one of the Lynch genes. Initially, the recommended course was that she just keep close watch, via regular internal exams with a scope. Then one of those exams revealed a small polyp. Within a year, it had swelled into a growth that completely encircled a portion of her colon. This wasn't cancer—but cancer is certainly what it would become, doctors insisted, unless decisive measures were taken. That meant radical preventative measures to remove not only the growth but places cancer might appear in the future. Like her colon. And her uterus. And potentially her ovaries.
Now the full calculus of life and death and risk and pain and prevention came into play. Her cancer-stricken cousin had left small children behind. Paula could not bear to think of her own kids growing up without a mother. She dutifully reported for the full program of excisions. She was 44 years old.
Not long ago, fatal vulnerabilities were known—so it was said—only to the gods. Mortality was fated. Then doctors replaced gods and that information passed into their hands for safekeeping. Now the so-called genomics revolution has changed the game again. It has passed that information on to us. This has complicated matters, for better and worse.
Genetic tests vary wildly in their predictive value— from absolutely definitive to so speculative as to be worth not much more than a horoscope. (This latter is the realm of direct-to-consumer outfits that cater mostly to healthy, curious tire-kickers—with no known hereditary risk of serious disease.) Fatal diseases are very rarely linked to a single gene—usually they are the product of an interplay of genes beyond the current understanding of scientists. So discovering you have a glitch in a snippet of DNA thought to be linked to a disease may be quite significant or not very significant at all. "Probability rather than certainty is the rule," says Edward McCabe, a Denver pediatrician and former president of the
American Society of Human Genetics. Usually, when someone's a candidate for a heritable disease, at least one piece of the puzzle—a reliable test or an effective treatment—is missing.
And so the era of widely available genetic testing has created a kind of laboratory for studying uncertainty: How well do we handle it?How clearly can we see our way through it?
Toxic Knowledge
"I think a lot of patients fall into the category of, 'If it doesn't tell me for sure then it's not that helpful,'" says Elizabeth Kearney, president of the National Society of Genetic Counselors.
Indeed, some of the most devastating diseases with a heritable component—from Alzheimer's to ALS—raise the specter of so-called "toxic knowledge." That's information that clouds rather than clarifies matters, ultimately doing more harm than good when testing positive isn't useful in any practical way because no cure exists for the disease. Proposed tests for these afflictions—like PET scans that could detect Alzheimer's years before a patient even starts showing symptoms—are tantalizing but as yet so murky that their chief virtue may be to present the "worried well" something more to worry about.
Gary Reiswig, a 71-year-old retired innkeeper and writer from East Hampton, New York, has thought longer than most about what constitutes toxic knowledge. Reiswig's family carries a rare and devastating gene mutation known as PS2 that causes early-onset Alzheimer's. Reiswig had a 50/50 chance of inheriting it, and he was terrified. (He documented his family's travails in his memoir, The Thousand Mile Stare.) But he ran between the raindrops: He is PS2-free.
What Reiswig did inherit was the ApoE4 gene mutation, which has been linked to Alzheimer's of the more common, later-onset variety. The two gene mutations—PS2 and ApoE4—are potentially quite different in their psychological blowback. PS2 is a relatively imminent death sentence. ApoE4 bequeaths a slightly elevated probability of eventually developing a disease you can't do much about anyway.
