Thursday, October 12, 2017

Of Jackalopes and Cancer

Science Fact: “Of Jackalopes and Cancer”
- Genomic Research Suggests Strange New Insights Into Disease -


Cancer. The word is both terrible and terrifying, as it should be. Even when the disease is not life-threatening or disfiguring, it’s life-changing. You hear your doctor say those words—“I’m sorry, it’s malignant, you have cancer”—and suddenly the monster under the bed is real. You can almost catch a glimpse out of the corner of your eye of the vultures circling above and behind you. You become acutely aware of that invisible life-clock in the palm of your hand, slowly blinking red.

No doctor ever says, “You have six months to live.” That only happens in overwrought dramatic fiction. The real medical science of it is nowhere near that precise. Oncologists like to speak in actuarial terms: of statistics, percentages, and probabilities. When my wife was first diagnosed with breast cancer, in August of 2010, I dove into the numbers. The median survival time for someone with her particular diagnosis was two years. The odds of her making it to five years were about 15%. Beyond that, long-term survival was, “anecdotal.”

At first you cry, and rage, and try to deny. Then you throw yourself heart and soul into the fight to beat this monster. You change your diet. You promise to exercise, just as soon as you feel better. You grit your teeth and tough it out through the surgery, the chemotherapy, the radiation, and whatever else your doctors decide to try. You knit stocking caps, to replace your lost hair and cheer up your friends in the chemo ward. You plaster pink ribbons all over everything, for the sake of “raising awareness.” The disease seems to activate the latent writer gene in a lot of people: you begin to chronicle your “cancer journey” and try to share it with the world. You participate in every fund raiser, charity run, and walk-a-thon that comes your way.

And then, if you're very lucky, you live long enough to begin to wonder: what’s going on with all that research, anyway? It’s been years. Weren’t we supposed to be closing in on a cure by now? So you begin to dive even deeper...

And you learn that actually, a lot of really incredible things have been happening with the research, and it’s all been in just the last few years. Widespread use of DNA sequencing is producing astonishing new insights into cancer that would be fascinating, if they were not also deeply disturbing.

To begin with, it may be a mistake to think of cancer as a spectrum of similar but different diseases that affect different organs: here a breast, there a kidney, here a lung, there a colon. It may be more accurate to think of cancer as a symptom—but of what?

We know that different types of cancers seem to run in different families. We know that different cancers seem to result from exposure to different environmental factors: viral infections, carcinogenic chemicals, ionizing radiation. But why aren’t the triggers consistent? We know there’s a proven link between smoking and cancer, but how do you explain the guy who smokes five cigars a day and lives to be a hundred? How do you explain the woman who never smoked a day in her life but got lung cancer when she was fifty?

The tip-off appears to be the genetic angle. For years, researchers studying the human genome have been puzzled by the presence of “junk” DNA: stuff that didn’t seem to belong in there and served no apparent purpose.

The answer to that puzzle has been found recently, and it turns out to be: it isn’t human DNA at all. About 8% of the human genome is endogenous retrovirus DNA. These are gene sequences that were inserted into our genome by the viral infections our ancestors survived—and we’re talking about our very distant ancestors. We share some of our endogenous retrovirus DNA sequences with bony fishes, and our evolutionary path diverged from theirs about 450 million years ago.

In the millions of years since, we seem to have settled into an uneasy symbiotic relationship with the retrovirus gene sequences our ancestors acquired. Some even changed the course of our evolution, by providing valuable services such as producing certain proteins necessary for ontogeny to recapitulate phylogeny. Endogenous retrovirus DNA sequences may be the reason why we are placental mammals and not marsupials.

And yet, all these accumulated foreign viral sequences remain within our genes, and researchers working with human stem cells have demonstrated that under the right conditions, they can be reactivated. Sometimes activating such a gene sequence merely kills the host cell. Sometimes the activated sequence surprises the scientists by in turn activating other seemingly unrelated sequences.

And sometimes, activating an ancient endogenous retroviral gene sequence causes the host cell to change, and to begin to exhibit behavior very much like that of a cancer cell.

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When my wife was first diagnosed with cancer in August of 2010, the literature said that survival beyond five years was “anecdotal.” It’s been more than seven years now, so I think in our cancer journey we’ve driven off the edge of the map, left anecdotal far behind, and crossed over into “mythical.” We know now that there is a genetic factor that predisposed her to develop this particular type of cancer, but I keep wondering: what was the trigger that caused this particular malignant gene sequence to “switch on?” How do we prevent its switching on in her sisters, cousins, nieces, and their daughters?

I keep coming back to viruses: simple, common, ubiquitous viruses, and the way that certain endogenous retrovirus sequences can activate other seemingly unrelated sequences. It’s been proven that there is a strong causal link between certain viruses and certain types of cancer. For example, I doubt there’s any adult left in North America who doesn’t know that there is a proven causal link between human papilloma virus (HPV) and cervical cancer.

But did you know that there is a similar virus—Shope papilloma virus (SPV)—that triggers the formation of bony tumors in rabbits? The tumors can form anywhere, but they’re particularly prevalent in and around the head. I’ve seen photographs of rabbits with SPV. Some look like they have tusks, or tree roots growing down from their lower jaws. Others look like they have...

Antlers.

And it’s precisely because the susceptibility to papilloma-triggered cancers is buried deep in the ancient mammalian DNA we share with rabbits, that researchers working with SPV were able to create a vaccine to prevent HPV, which has been the cause of so much controversy of late.

As I said: we’ve driven off the edge of the known world and are entering mythical territory now, or at least the realm of cryptozoology. Exciting times ahead.

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