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When European explorers and fishermen began to frequent Canada’s shores in the 16th century, they brought with them a plethora of tools and trinkets, including knives, axes, kettles, and blankets. The region’s indigenous people traded the Europeans for these items, swapping the one thing they had in abundance—animal pelts. The furs quickly became popular in Europe, and by the early 17th century, the French had established permanent posts in North America to facilitate trade. Little did the natives know that in addition to receiving metal and material goods for their furs, they were also acquiring a strain of Mycobacterium tuberculosis, the causative agent of tuberculosis (TB).
The first time Stanford University infectious disease specialist Caitlin Pepperell saw the DNA fingerprints of a sampling of tuberculosis bacteria from Aboriginal peoples in Ontario, she says she “pretty much knew” the bacteria were related to the Mycobacterium tuberculosis strains she had studied as part of her research on TB evolution in Saskatchewan. But that didn’t quite make sense. Indigenous communities in the two provinces were more than 1,000 miles apart and were composed of distinct ethnic groups. “I wouldn’t have expected them to be in much contact,” Pepperell says. So how did such isolated groups of people, spread across vast expanses of Canadian territory, come to share a remarkably similar pathogen?
Pepperell contacted researchers around Canada, including Wendy Wobeser of Queen’s University in Toronto, who had sent Pepperell the Ontario fingerprints, to organize a collaborative project to track the evolution of M. tuberculosis through Canadian history. Sure enough, M. tuberculosis strains from indigenous populations in Ontario, Saskatchewan, and Alberta, as well as strains from French Canadians in Quebec, all appeared to comprise a single lineage, characterized by a shared nitrogenous base deletion called DS6Quebec. The minisatellite data suggested that the bacteria spread among the continent’s Aboriginal populations from a source population in Quebec, accompanying European fur traders as they set up trading posts further and further west. Historical records show that European immigrants and Canada’s indigenous populations socially interacted, and even intermarried—arrangements which made M. tuberculosis transmission likely. Though Pepperell admits that the idea sounded a little “crazy” at first, the more she dug into the data, the more she was convinced that the fur trade was the vehicle for widespread gene flow of a single lineage of M. tuberculosis among Canada’s indigenous populations.
“This is a very neat story,” says mathematical biologist Carlos Castillo-Chavez of Arizona State University, who was not involved in the research. “This is almost like the anthropology of disease—the impact of people’s mobility and migration patterns on disease evolution.”
“It’s really the most robust description of [tuberculosis] epidemiology in northern Canada,” adds Wobeser, a coauthor of the study, published in a recent issue of PNAS (108:6526-31, 2011). Though she suspected the Canadian TB strains were related from the start, she says she wouldn’t have predicted that the link dated as far back as the fur trade. “But now that I know it, it makes sense.”
The data also suggest that M. tuberculosis can persist in populations at very low levels for long periods of time, exploding into epidemics as soon as host conditions are favorable. Indeed, though the initial spread of the bacteria likely started as early as 1710, tuberculosis was not commonly seen in indigenous populations until outbreaks in the 19th and 20th centuries.
One possibility for this delay, Castillo-Chavez says, is that the continued colonization of Canada by European settlers disrupted the Aboriginal lifestyle. “This is just a suspicion,” he says, but “my perspective is that TB activation requires some weaknesses in the immune system, and I think that those weaknesses may stem from problems of nutrition”—such as may have occurred as a result of a shift in “the balance of powers” during colonization.
Regardless of the reason, the finding that M. tuberculosis can persist at such low levels in the population may explain why the bacterium is so difficult to eradicate, Pepperell says. “Probably the most interesting part is the fact that we can learn so much about the evolution of the bacteria and the evolution of epidemics by integrating this sophisticated genetic analysis with historical research,” she says.