The Gene Bubble: Why We Still Aren't Disease-Free

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Photographs by Phillip Toledano

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Photographs by Phillip Toledano

Ernest Hemingway's writing may have tended to the short and sharp, but the man himself was apparently fond of the cuddly and extraneous, at least when it came to kittens with too many toes. A sea-captain friend of Hemingway's, it seems, persuaded him to take in a polydactylic cat, and that cat became the progenitor of a colony of overly toed felines thriving today in and around the museum in Key West that was Hemingway's home. The patterns of inheritance among those cats have even helped shed a bit of light on certain defects in human DNA. And so it is that Papa retroactively became an early contributor to the science of the human genome.

I learn this from Nadav Ahituv, a rising-star geneticist at the University of California, San Francisco, Medical Center, who studies the genetic roots of limb-related defects, obesity, and drug absorption. Congenital defects hold a special significance for Ahituv: As a teenager, he was in a body brace for three years with scoliosis. "It was not fun," he says. "I spent my time reading Kafka, and then I started in on genetics textbooks, thinking that if I could understand what had gone wrong with me, maybe I could find a way to help others." It must have been time well spent, because Ahituv, a fit-looking fellow who gets to work by propelling a folding bike up the city's famously steep hills, has shown an uncanny knack for tracking human traits and disorders down to specific sections of DNA. He can now point out limb-altering segments of chromosomes as easily and precisely as he might map out coffee shops in the Lower Haight.

This is exactly the sort of progress we've come to expect from the triumphant cataloguing of the human genome, first accomplished in rough form in 2000 after a decade of work, and then polished up by 2003; researchers have since been amassing and analyzing genomic data at an ever-accelerating rate. The genome, as we all know, largely determines what we look like, our traits, and, significantly, our susceptibility to disease and other disorders. Ahituv is one of tens of thousands of well-funded researchers around the world trying to determine which segments of the genome contribute to which disorders. It is one of the biggest scientific endeavors in history, premised on the notion that the results can be used to prevent or fix many things, or possibly everything, that ails the human body -- from allergies to cancer to aging itself. Dozens of biotech companies have sprung up in the past decade to commercialize this work, and one might assume that a stream of miracle pills will soon be on its way to our pharmacies.

You bet -- just as soon as we work through a couple of hitches in this grand genomic enterprise. Scientists have indeed been superb at finding connections between disorders and various strips of DNA. But it turns out that in the vast majority of cases, these connections happen to be hideously convoluted, with any one disorder related to many genes and any one gene affecting many things in the body. Even when researchers are able to highlight a clear relationship between a single gene and a single disorder, they generally have little or no idea how those chunks of DNA are causing problems. Then there's the disturbing tendency of gene-related treatments either to fail to work on the vast majority of people or else to entail horrific side effects. "Most individual elements of the genome can be perturbed, and there won't be any substantial consequences," says John Sninsky, vice president of discovery research for Celera in Alameda, California, the first company to sequence the genome. "Except for when there are catastrophic consequences."

Yes, we've cracked the genome. Experts can identify every one of the 3 billion bases in every micrometer of DNA in any cell in your body. But so far, that has given the medical world no more ability to treat or predict most illness than knowing that Al Qaeda is camped out in Waziristan has allowed the U.S. government to clean up terrorism or predict where it will strike next. In fact, while thousands of links have been catalogued in journals and trumpeted in the media, with precious few exceptions virtually no promising new treatments or even highly useful diagnostics have emerged. And the situation is unlikely to improve much anytime soon. I happened to speak with prominent genetics researcher Russ Altman of Stanford on the 40th anniversary of the Apollo moon landing, and he was worried that the public might ultimately see genomic research in the same way: as an amazing feat with little practical payoff. "People said, 'All that effort to put someone on the moon, why the heck did we do that?' " he told me. "Apollo did have lots of smaller spin-offs, like better jet engines, but I just hope the impact of the genome on our lives is more obvious than that 40 years from now."