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Dr. Robert Hegele is shown in this 1998 photo. (Tibor Kolley/The Globe and Mail)
Dr. Robert Hegele is shown in this 1998 photo. (Tibor Kolley/The Globe and Mail)

How the diabetes-linked 'thrifty gene' triumphed with prejudice over proof Add to ...

But they didn't. In fact, he says, "newer genetic data suggest it's incorrect to pin the blame for type 2 diabetes on a single gene in any population. Environmental or lifestyle factors are the key ingredients." Susceptibility appears to involve "a diverse network of dozens or hundreds of genes, each of which plays a very small part," he says - "genetic factors that can be found across all human populations."

Dr. Hegele, now director of cardiovascular research at UWO's Robarts Research Institute, says he once had "an unquestioning acceptance" of Dr. Neel's theory, and liked the way it invoked Charles Darwin and the pressures of evolution and adaptation. More recently, "the whole thrifty-gene idea seems to me not to capture the subtlety and complexity… of type 2 diabetes in first nations communities."

A chronic condition, type 2 diabetes occurs when the body makes too little of the insulin it needs to metabolize glucose, its fuel source, or is unable to use the insulin properly. Obesity is a leading risk factor. Dr. Zinman says it was reasonable to search for the role that genes may have played.

And former chief Harry Meekis, who helped to negotiate the research agreement, said at the time, "We didn't want to be known as the people with the third-highest rate of diabetes - we wanted to be the community that did something about it."

International press coverage of the finding at Sandy Lake helped to cement the thrifty-gene theory in the public consciousness - and spark a backlash from academics such as Prof. Poudrier. She was completing her PhD at Queen's University when she read of the discovery, and it drew her deep into the underpinnings of the famous Neel theory.

 "There was a lot of cultural panache around the notion of genes at the time," she says, "and it was born in the thick of the eugenics movement."

Indeed, in his landmark paper, published in the American Journal of Human Genetics in 1962 (just nine years after the double-helix structure of DNA had been discovered), Dr. Neel suggests running blood-insulin tests on "primitive hunters and gatherers." He also includes a section entitled "Some Eugenic Considerations" in which he says that, if correct, his theory poses an ethical dilemma because "modern medicine makes it possible for diabetics to propagate," allowing the disease to spread. But intervening to eradicate the gene could backfire, he added, if famine ever returned on a major scale and it was required again.

Indirect evidence to support the theory was bountiful after Dr. Neel proposed it - a mouse with a mutated gene that led to obesity and diabetes, research surveys showing famines could kill off more than a quarter of a population and, most compelling, the sudden spike of obesity and diabetes in aboriginal communities where none had existed before.

Aberdeen's Prof. Speakman feels it's easy to understand why the hypothesis has been so highly regarded. "Because it's a great idea: 'In times of famine, it's the lean ones who are gonna die.' It's a simple idea; it all makes sense."

Except that it's wrong, he adds. There is no proof that fatter people survive famines better than thinner ones. In fact, says Prof. Speakman, a specialist in how animals use energy, throughout evolution, "most populations would never see a famine. There's one every 100 years or so, but in those times, people only lived 25 or 30 years."

Anthropologists have long argued the theory wrongly assumes that all hunter-gatherers suffered regular famines, when crop failures made starvation more common among early farmers, suggesting Europeans should face a greater risk of being obese and diabetic. Farming arose about 12,000 years ago - which, in evolution, is like the day before yesterday - and not enough time, says Prof. Speakman, for alleged thrifty genes to have spread as widely as they seemed to have.

That such arguments have been missed, or dismissed, by biomedical researchers comes as no surprise to him. "People who are medically trained are not well trained in evolutionary biology," he says.

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