Guns, germs and furs

If you’re interested in looking at how the migration of a microbe into new populations can affect its evolution, the ideal setting for your study is probably a situation where an infected population meets a population that has never been infected before.  It helps if the contact between the two populations is limited, so that you can trace the infection more precisely; and it’s even better if the infection happens in neighboring populations at different times.  All of these conditions applied in Canada in the early 18th century to mid 19th century, when Mycobacterium tuberculosis was spread from French settlers to indigenous Canadians as a result of contacts made while trading furs.  The resulting patterns of M. tuberculosis dispersal have now been described in a recent paper (Pepperell et al. 2011.  Dispersal of Mycobacterium tuberculosis via the Canadian fur trade. doi:10.1073/pnas.1016708108).

Much of Canada was completely isolated in the 18th century.  The European settlers initially didn’t penetrate very far beyond the Atlantic seaboard.  It was the fur trade that created the impetus for developing a vast network of transportation routes, largely based on canoes, that connected the interior with the growing settlements at the edges.  The trade also offered career options for fur company employees: guides, translators, navigators and negotiators, and especially the voyageurs who traveled deep into the mysterious interior of Canada to bring back the furs.  [The lives they lived look pretty miserable to us now: 14-16 hour days of constant paddling, occasionally interrupted by a portage, in which they would carry at least 180 pounds of furs — repeatedly — across rugged terrain.  They often suffered hernias, and they ate mostly pemmican (dried bison meat), but they sang a lot, and so are now considered deeply romantic figures.]

A normal voyageur contract for a so-called “homme du nord” was 2 years long, because it was impossible to get all the way up to the north and back before winter hit.   Many stayed much longer; one analysis of trader residence patterns estimated that the average trader spent 16 years in the interior.  Many traders married, or “married”, native women, and had children who were dubbed the Métis, now a significant ethnic group in Canada. Though the fur trade was important, the number of voyageurs was not enormous: in the first half of the 18th century, there were only between 50 and 150 employees of the fur trade companies in the interior, and even at the beginning of the 19th century this number was only ~1600.  Around 1870, the traditional fur trade ended, and so did the migration; Pepperell et al. estimate that the total number of individuals who migrated from Eastern Canada to the west and interior during the 160 years when the fur trade was active was 5,419.  These are the patterns that shaped the social network that in turn shaped the transmission of M. tuberculosis in this population.

Some major fur trade routes, travelled by canoe and portage. My sketch, from Pepperell et al.'s data.

You know all about M. tuberculosis, of course.  It’s the main cause of tuberculosis, TB, a disease of the lungs (and skin, and bones) that used to be called consumption.  It’s one of the world’s great killers.  It used to be called the King’s Evil, because there was a superstition that the touch of a king would cure the glandular swellings associated with TB.  It’s estimated to have killed more people than the black death, leprosy or HIV, and currently infects about 1/3 of the world’s population.  Thomas Mann’s The Magic Mountain describes the one semi-effective treatment for pulmonary TB available in the 19th century, fresh air.  This is the infection that the fur trade spread within the indigenous population of Canada’s interior.  Fortunately, most infections are silent: despite the endemic infection with TB bacteria, “only” about 9-10 million new symptomatic cases pop up per year.  But the drugs we have available to control the disease are losing their efficacy, as multi-drug-resistant TB becomes more common.  So understanding how the bacterium spreads is a really important goal.

In a survey of the current distribution of M. tuberculosis variants, Pepperell et al. found that a single bacterial lineage, DS6(Quebec) is dominant throughout Canada, in the French Canadians of Quebec as well as the aboriginal populations in Ontario, Saskatchewan and Alberta.   By looking at DNA variation in minisatellite loci in the bacteria in these different areas of Canada, Pepperell et al. found evidence that the DS6(Quebec) lineage was introduced into the population long ago. There’s also evidence that it underwent rapid population expansion, consistent with the idea that it might have been introduced into new human populations. DS6(Quebec) appears to have been freely spread back and forth between the different human populations for a period of about 100 years.  These days, the French Canadians of Quebec have relatively little contact with the aboriginal populations studied here, but in the days of the fur trade there was more interaction.  There’s a nice fit between the times that the fur trade was operating and the predicted time in which cross-infection by M. tuberculosis probably occurred.  Also, the number of DS6(Quebec) haplotypes is highest in Quebec itself, consistent with the idea that the European settlers brought a varied population of bacteria with them from Europe.  Then, through the limited number of voyageurs, they passed on a small subset of these variants to the aboriginal populations.

There is an interesting internal control within the aboriginal data: the populations in Saskatchewan and Manitoba had groups that were largely cut off from the industrialized society represented by Quebec until the early 20th century.  Alberta, in contrast, had no such remote regions.  So if the TB bacteria were spreading from Quebec, Alberta should look more like Quebec than do Saskatchewan or Manitoba.  Indeed, bacterial diversity in Alberta is high relative to the other two regions, and if you subdivide the groups within Saskatchewan and Manitoba further, into historically “remote” and “non remote” groups, the diversity in non-remote groups is similar to that in Alberta, while the remote groups have lower diversity.  So: everything is consistent with an early transfer of a small number of bacterial lineages quite a long time ago.  There is also evidence for a later additional transfer of different bacterial lineages in the non-remote populations in the early 20th century.  This later transfer came after the interior of Canada became enormously easier to get to — modern forms of transportation have a lot to answer for — and large numbers of European immigrants started to settle in previously untouched regions.  But the transfer of bacteria from European immigrants to native populations is surprisingly rare in this later period, probably because the new immigrants were socially much more distant from the natives than the voyageurs could afford to be and still survive.

One interesting conclusion that comes out of this study is that the dispersal of M. tuberculosis bacteria to native populations seems to have happened about 100 years before the first recorded epidemics of TB.  The advent of railway networks, steam ships that conveyed visitors to the western half of Canada, agriculture, resettlement and overcrowding (and perhaps the loss of that pure air that was the 19th century’s only treatment for pulmonary TB) correlated with the first outbreaks of epidemic tubercular disease.  It’s not clear whether these findings, which are based on a very small number of people (the voyageurs) spreading a limited set of bacterial lineages, apply more broadly.  If they do, though, this could help explain why TB has been so hard to eradicate: the spread of M. tuberculosis may be silent, and tiny populations of the bacteria may spread over large distances without anyone noticing until it’s too late. Brrr.

Pepperell CS, Granka JM, Alexander DC, Behr MA, Chui L, Gordon J, Guthrie JL, Jamieson FB, Langlois-Klassen D, Long R, Nguyen D, Wobeser W, & Feldman MW (2011). Dispersal of Mycobacterium tuberculosis via the Canadian fur trade. Proceedings of the National Academy of Sciences of the United States of America PMID: 21464295.
A note on the title: if you haven’t yet read Jared Diamond’s brilliant book, Guns, Germs, and Steel: the fate of human societies, do.