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The film crew that gathered in the lab of Repeat Diagnostics in North Vancouver was not quite ready for Gary de Jong’s cheerful question: “Who here wants to know when they’re going to die?” De Jong, who runs the startup and also works for the BC Cancer Agency’s Terry Fox Laboratory, scanned the faces of his visitors. Everyone looked taken aback. It’s strange to hear one of the biggest questions of all so casually floated. This was knowledge only the gods are meant to have.
Repeat Diagnostics specializes in a genetic test called a telomere-length flow-FISH analysis, a technique pioneered by Vancouver geneticist Peter Lansdorp, who runs a lab at the BC Cancer Agency and lectures in the UBC Department of Medicine. A client’s blood sample is sent through a machine called a cyclometer, which is about the size of an espresso machine but costs 3,000 times more. Blood cells pass one by one through lasers, and an accurate measurement is taken of the length of the telomeres.
“Telomere” is one of the buzzwords of the genomic age, and the story growing around this piece of DNA is starting to resemble the Da Vinci Code, complete with breathless predictions of huge payoffs—cancer conquered! lives fantastically extended!—once its secrets are unlocked. Last year, research into telomeres won the Nobel Prize in physiology.
Yet the workings of this obscure genetic molecule have been difficult to understand. Until recently, we had no idea why it was there. Telomeres are not part of your genetic signature; they’re just repeating sequences of molecules called nucleotides that sit there at the end of the table like the manuscript of a stir-crazy Jack Nicholson in the Shining, cryptic and foreboding.
Telomeres, scientists now know, do serve a purpose. If you think of a chromosome as a shoelace, the telomere is like the little plastic tip that keeps it from fraying. Without it, the sticky ends of our chromosomes would glom together, producing mutations, and you’d get sick and die in a hurry. Like chromosomes, however, telomeres degrade. Eventually they become too short to properly protect the chromosomes. The new cells coming off the line start looking like the duds Kinko’s promises not to charge you for, and your body sounds a self-destruct alarm. This is part of the aging process. (According to one theory, if we could find a way to stop our telomeres from shortening we’d live forever.)
De Jong was being provocative with that film crew. His lab’s test can’t actually predict your death date—the science is too young and there are too many variables. But the length of your telomeres is a useful metric to understand how healthy you are. It can signal increased risk of various afflictions, most rare but some, early research suggests, as potentially common as heart disease. “The profile gives you a picture of your health, in a way,” de Jong says. Very short telomeres are red flags. A defect may lurk in your genome, making you vulnerable to serious illnesses. Or short telomeres could mean that your cells have been rapidly dividing as they battle some other disease or stressor. Either way, if you’re still relatively young, and your telomeres are very short, says de Jong, “there’s something going on in your body, in your life.”
Each week, at Repeat’s plain office near Lonsdale Quay, around 20 samples arrive by courier from all over the world. Most are from American physicians treating seriously ill little kids, and wondering if they have a case of childhood leukemia on their hands. A very short telomere count would support that diagnosis, and speed up or change the course of treatment. And because some leukemias are hereditary and the best donor is often a sibling who might herself be incubating the disease, screening the donor before a transplant might avert a fatal gift. Lansdorp was overwhelmed at the BC Cancer Agency with requests from doctors to measure telomeres. “That’s why we set up the company,” says de Jong of the partnership. They wanted to save lives.
But Repeat’s customer base isn’t just critically ill kids. It’s also healthy boomers who are hell-bent on staying young through any means. Many are on expensive regimens of experimental drugs laced with synthetic telomerese. One, the anti-aging supplement TA-65, discovered by biotech giant Geron Corp. and licensed to T.A. Sciences (a Repeat Diagnostics client), is touted as a “proven telomerese activator.” If your telomeres are short, goes the pitch, you need TA-65 to get back to top form. If your telomeres are ordinary, you really need TA-65, because extraordinariness beckons.
Last year, two vials arrived at Repeat Diagnostics via FedEx from Chicago. One contained the blood of Oprah Winfrey, the other of her sidekick Mehmet Oz. Oprah was preparing a show about aging, and both she and “Dr. Oz” got their telomeres assessed in de Jong’s lab. In the episode, Dr. Oz held up a shoelace, the better to explain these magic things called telomeres and what they can tell us about our “true” age. Then he produced Oprah’s chart. You could see the curve of “normal” telomere length plotted across an average human lifespan, and the big dot where Oprah’s score fell. The dot sat above the age-matched control. Dr. Oz took out a ruler and drew a line back to the curve. Oprah was in good shape, he said; she had a biological age of a woman 10 years younger. (Cue the applause.)
Oprah did not mention Repeat Diagnostics, and you’d think that would have irked de Jong and Lansdorp: businesswise, a testimonial from the TV host is a double-helix to heaven. But they were relieved. They didn’t want to be linked to such an exaggerated claim. “You can’t say of 56-year-old Winfrey, ‘Your body is 45 years old,’” de Jong told me. “This is just a theory. And we as a company can’t theorize; we have to give fact.”
Like Oprah, 55-year-old Vancouverite John Bigsby was merely curious when he sent a blood sample to Repeat five years ago. The results were a shock: his telomeres were so short they fell below the first percentile. A year and a half later, he was diagnosed with pulmonary fibrosis, a rare disease linked to a genetic defect. The disease produces scarring in the lungs and slowly shuts down their function. Bigsby almost died. (He had a successful lung transplant, although like most recipients he will be on anti-rejection medication for the rest of his life.)
The story underlines both the power and the shortcoming of the telomere test. A test detected signs of an affliction that would have been hard to find any other way, but it left a question mark about causality. Did the gene cause the short telomeres, or did the disease cause the short telomeres because scarring was occurring in the lungs and the telomeres shortened trying to fight it? Also: the test didn’t save Bigsby’s life. There was nothing to seek treatment for until a wicked cough sent him to the doctor, who ordered the tests that flagged the disease. But that bit of foreknowledge changed his life. Knowing something sinister may be ticking in your genome raises the stakes. It sharpened his appreciation of every day above ground, and prompted rigorous adherence to, as he puts it, “doing everything right.” His children have a chance of inheriting the mutation and developing pulmonary fibrosis. “I’ve asked them if they want to be tested and they’ve said no. They’re still in their late-teens and early 20s,” he says. “They still believe they’re going to live forever.”
“John Bigsby” is a pseudonym. Turns out, there can be many reasons why Bigsby would want to keep some of this information private, as I discovered when I applied to get my own telomeres measured. Here’s the procedure: you visit Repeat’s website and download a requisition form. You get the form signed by a “requesting physician,” then take it to a lab, where you give a sample that’s couriered to Repeat in North Vancouver. (The test costs $400.) I dropped off the form with my family doctor for what I thought was his perfunctory John Henry. When I got home there was a phone message: “Please make an appointment to talk about this.”
“I’m prepared to do this for you,” my doctor said when we met, “but I want you to think about whether you really want to.” He rolled his chair in close. “You start turning over rocks, you may regret it.” Whatever the test might flag becomes part of my medical records. Insurance companies will ask for those. “It’s a Pandora’s box,” he said. “Once you open it, you have to live with it.” Fledgling genetic discrimination laws in the U.S. prevent employers from denying you a job or health care providers from denying you insurance based on your genetic profile. (The law hasn’t snared life insurers yet.) Canadians as yet have no such protection.
With visions of a Gattaca future in mind, I called Timothy Caulfield, the Canada Research chair in Health Law and Policy and a professor at the University of Alberta’s law school, who’s working on a book on the implications of genetic testing. “Yes, your insurance company could use that information, but I can’t imagine why they’d want to,” Caulfield said. “They can ask about your blood pressure, your cholesterol, how your relatives died.” Right now, “all this is vastly more predictive than the length of your telomeres.”
Good to know. Maybe a day will come when we’ve cracked the Da Vinci Code, and our telomeres will become important markers of all sorts of health risks and also a lever to fix them. (And the test will be cheap as soup.) Until then, I’ve decided I can live my life without knowing if I’m better endowed, telomerically, than the next guy—however long that life turns out to be. VM