AIDS and the Black Death
Sir,
Cohn and Weaver1 assert that recent publications suggesting that the medieval Black Death could be responsible for the origin of the CCR5-
32 allele2–4 are mistaken. They say: ‘scientists ... have assumed that the north-south European geographical cline in the frequency of the CCR5-32 allele among present-day descendents parallels the severity of the Black Death in 1348 ...’ and ‘it is erroneous to assert that the plague mortalities exhibit a north–south cline; rather the opposite seems to be the case’. It is unclear who is supposed to have made these assumptions, or asserted this north–south cline. Published research indicates such assumptions to be unsubstantiated and counter to modern Black Death understanding.
Cohn and Weaver argue that if the Black Death were responsible for the spread of the CCR5-32 allele, then present-day frequencies of the allele should correlate positively with recorded mortality during the Black Death. As Italy suffered greater mortality than Scandinavia during the time of the Black Death, yet but has a lower sampled CCR5-32 allele frequency, the Black Death cannot be responsible. However, it is not clear that this argument is conclusive.
Firstly, it is not obvious whether we should expect high Black Death mortality to correlate with high levels of CCR5-32 (because of the Black Death selectively killing those who lacked the allele) or low levels (because populations lacking the allele would be more at risk from the disease). In other words, how much the distribution has been shaped by selection, and how much it reflects pre-Black Death variation. As we do not know the frequency of the CCR5-32 allele in European populations at the time of the Black Death, this question seems unanswerable.
Secondly, it is unclear to what extent the present-day distribution of the allele reflects that 700 years ago. It is general knowledge, for example, that immigration and population mixing over that time have been far more pronounced in southern and central Europe than in Scandinavia. Over time, migration would be expected to dilute selection effects from disease, once those diseases were no longer epidemic. ‘Black Death’ epidemics in Scandinavia continued well beyond the time at which they died out in southern Europe.2 As Cohn and Weaver note, Finland did not experience the plague until 1440, almost 100 years after the disease entered southern Europe. This would tend to favour a higher level of CCR5-32 allele in Scandinavia, as observed. Other diseases may also have affected this distribution, although modelling suggests that smallpox5 could not have elevated CCR5-32 allele frequencies to those witnessed in Europe today.3
Martinson et al.6 found a cline of the indigenous population demonstrating detectable levels (>1.5%) of the CCR5-32 allele, from central Asia through southern Europe and extending up to the Arctic Circle: frequencies of the CCR5-32 allele were lower but detectable in Central Asian and Middle Eastern populations and higher in Scandinavian and northern Russian populations. This appears to correspond to the theory that the Black Death began in central Asia, spread along trade routes to the west and then traveled northward through Europe until reaching the Arctic Circle, though again interpretation is not simple.
Cohn and Weaver's conclusion that ‘... there is no connection between plague and the HIV-resistant allele’ seems at best premature. In time, the posited relationship between the Black Death and the CCR5-32 allele may indeed turn out to be a red herring. For now, multiple lines of research continue to raise more questions than answers about the world's greatest recorded historical epidemic.
Valdosta State University
Valdosta
Georgia
USA
email: bhbossak{at}valdosta.edu
References
1. Cohn SK and Weaver LT. (2006) The Black Death and AIDS: CCR5-32 in genetics and history. Q J Med 99 497–503.
2. Scott S and Duncan CJ. (2004) Return of the Black DeathHoboken, NJ Wiley.
3. Duncan SR, Scott S, Duncan CJ. (2005) Reappraisal of the Historical Selective Pressures for the CCR5-32 mutation. J Med Genet 42 205–8.
4. Duncan CJ and Scott S. (2005) What caused the Black Death? Postgrad Med J 81 315–20.
5. Galvani A and Slatkin M. (2003) Evaluating Plague and Smallpox as Historical Selective Pressures for the CCR5-32 HIV-resistance allele. Proc Natl Acad Sci USA 100 15276–9.
6. Martinson J, Chapman N, Rees D, Liu Y-T, Clegg JB. (1997) Global Distribution of the CCR5 gene 32-base pair deletion. Nat Genet 16 100–2.[CrossRef][Web of Science][Medline]
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