Robert Hegele had doubts. Even in 1999, as the research attracted wide media attention and the British Medical Journal declared, "Thrifty gene identified in Manitoba Indians," Dr. Hegele could not be certain - which is telling, since he was the geneticist who had made the discovery.
But back then he still thought further work would bear it out. Part of a small research group, Dr. Hegele had been studying the astonishing prevalence of type 2 diabetes among the Ojibwa-Cree people of Sandy Lake, an isolated reserve in Northern Ontario not far from the Manitoba boundary.
At that time, gene hunting in remote populations was as fashionable as starting a dot-com, and the Sandy Lake project stood out as a model - a rare instance in which a community negotiated compensation for the DNA of its members. In exchange for fresh food, expanded medical services, school programs and a share of any profits, the band council allowed scientists to search for an explanation as to why the diabetes rate was five times the national average - why, in fact, it was the third-highest rate in the world.
The locals knew it as the Sho-goh-wah-pee-nay, the "sugar disease." It afflicted nearly half the adults, could be detected in children as young as 10 and cost many residents their kidneys, sight and limbs. Yet Sandy Lake had recorded no cases of diabetes until the 1960s.
The numbers seemed to have risen alongside its conversion to the unholy trinity of the couch, fast food and the television. When Dr. Hegele, a senior scientist at the University of Western Ontario, first heard the Sandy Lake story, he couldn't help but wonder if this was the work of the elusive thrifty gene.
Since James Van Gundia Neel proposed it almost 50 years ago, the thrifty-gene hypothesis has reigned as the dominant explanation for soaring rates of obesity and diabetes among many aboriginal groups. Native communities where diabetes didn't exist in the first half of the 20th century had, by the end of it, the world's highest prevalence, with Arizona's Pima Indians in first place, followed by the Nauru islanders of Micronesia and the Oji-Cree at Sandy Lake.
Dr. Neel, an influential geneticist at the University of Michigan, felt that genes were partly to blame. He speculated that genetic traits among the world's prehistoric hunter-gatherers enabled them to store calories during times of feast in order to survive in times of famine.
But with "the blessings of civilization," he wrote, these thrifty genes had become hazardous baggage in a sedentary world of all feast and no famine, predisposing carriers to obesity and the diseases it brings.
His idea spread like an epidemic, embraced by everyone from public-health officials and policy-makers to the media and many aboriginal people themselves. Although never billed as more than a hypothesis, it came to be seen as fact - "a scientific axiom," Dr. Hegele says, "dogma almost."
But now, with obesity and diabetes shaping up to be a global pandemic, the theory appears to be dying - raising the prospect that prejudice more than proof gave it such a long life.
A bevy of researchers now questions it. Even true believers such as Dr. Hegele are losing faith; some dismiss it out of hand. Not least because, after four decades in search of thrifty genes, no one can find them.
Even huge genome-wide hunts involving thousands of subjects and boutique projects using the latest technology have come up empty, while the many genetic variants now linked to diabetes and obesity have turned out to be no more prevalent among aboriginal people than anyone else.
Jeffrey Friedman, the renowned Rockefeller University scientist who discovered the appetite-suppressing hormone leptin, has been hunting the thrifty gene since the mid-1990s on the Pacific island of Kosrae. Sixty years ago, its people were lean, living off the land and sea, but after the U.S. started shipping them soft drinks, Spam and processed foods, three-quarters of Kosrae's residents have become overweight, if not obese.