Experts argue over whether smallpox or plague should take the credit.

Deaths from plague in the Middle Ages may have left more people with a gene that guards against HIV. Credit: © AP Photo

Devastating epidemics that swept Europe during the Middle Ages seem to have had an unexpected benefit - leaving 10% of today's Europeans resistant to HIV infection.

But epidemics of which disease? Researchers claimed this week that plague helped boost our immunity to HIV, but rival teams are arguing that the credit should go to smallpox.

What is clear is that something has boosted the prevalence of a mutation that helps protect against the virus. The mutation, which affects a protein called CCR5 on the surface of white blood cells, prevents HIV from entering these cells and damaging the immune system.

Around 10% of today's Europeans carry the mutation, a significantly higher proportion than in other populations. Why is it so common in Europe? One possibility is that it favours carriers by protecting them from disease. But geneticists know that the mutation, called CCR5-Δ32, appeared some 2,500 years ago - long before HIV reared its head.

“You need something that has been around for generation upon generation. Christopher Duncan , University of Liverpool, UK”

"You need something that has been around for generation upon generation," explains Christopher Duncan of the University of Liverpool, UK, who led the latest analysis. Plague fits the bill, he and his colleagues conclude from a mathematical modelling study published in the Journal of Medical Genetics1.

Repeated outbreaks

Duncan's team points out that when the Black Death first struck, killing some 40% of Europeans between 1347 and 1350, only 1 person in 20,000 had the CCR5-Δ32 mutation. As the centuries wore on, repeated outbreaks, culminating in the Great Plague of London in the 1660s, have occurred in tandem with rises in the mutation's frequency.

Other experts are not convinced, however. A similar study2 published in 2003 suggests that it was smallpox that boosted the mutation's frequency. "Smallpox would still be my favoured hypothesis," comments Neil Ferguson, an infectious disease expert at Imperial College in London, who was not involved in the study.

“Smallpox would still be my favoured hypothesis. Neil Ferguson , Imperial College, London”

Duncan counters that smallpox has only been a serious threat in Europe since the 1600s, which may not have been enough time to have such a big genetic effect. But Ferguson argues that the influence of smallpox over the centuries may have been underestimated, because it largely affected children.

"Smallpox seems the most parsimonious explanation," he adds. He points out that one major problem with Duncan's plague theory is that it requires a rethink of how plague was caused. If those with a virus-blocking mutation were more likely to survive, it follows that plague would have been caused by a virus. But the conventional view is that the plague epidemics of the Middle Ages were caused by a bacterium, Yersinia pestis.

Rats off the hook

Duncan admits that his theory is difficult to prove. But he argues that the outbreaks are easier to explain if one assumes that plague was passed directly from person to person as a virus, rather than the 'bubonic plague' that was caused by bacteria carried by rats and their fleas. "Rats are absolutely in the clear for Europe," he argues.

If that's true, then Duncan can explain not only the mutation's average levels in Europe, but also the fact that people in Finland and Russia have the highest level, around 16%, whereas a mere 4% of Sardinians possess it.

He points out that outbreaks of feverish viral disease continued in Scandinavia and Russia for far longer than in the rest of the continent, reinforcing the mutation's status as a valuable asset. "It was mouldering on until about 1800 in northern Europe."

References 1 DuncanS. R., ScottS. & DuncanC. J. J. Med. Genet. 42, 205 - 208 (2005). 2 GalvaniA. P. & SlatkinM. Proc. Natl Acad. Sci. USA 100, 15276 - 15279 (2005). Download references

Authors Michael Hopkin View author publications You can also search for this author in PubMed Google Scholar

Additional information University of Liverpool, UKImperial College, London

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