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The (Short) Evolution of Smallpox

New research suggests that smallpox, a viral disease that caused millions of deaths worldwide, may not be an ancient disease[1]. The findings raise new questions about when the Variola virus first emerged and later evolved, possibly in response to inoculation and vaccination.
Smallpox, one of the most devastating viral diseases, had long been thought to have appeared in human populations thousands of years ago in ancient Egypt, India and/or China, with some historical accounts suggesting that pharaoh Ramses V, who died circa 1145 BC, suffered from smallpox due to lesions found on his face.

To better understand its evolutionary history, scientists extracted the DNA, from partial mummified remains of a Lithuanian child, interred in the crypt of a church in Vilnius, believed to have died between 1643 and 1665, a period in which several smallpox outbreaks were documented throughout Europe with increasing levels of mortality. Researchers compared the 17thC strain to those from a databank of samples dating from 1940 up to its eradication in 1977. Surprisingly, the results shows that the evolution of smallpox virus occurred far more recently than previously thought, with all the available strains of the virus having an ancestor no older than 1580 AD.

The pox viral strains, that represent the true reservoir for human smallpox, remains unknown to this day. Camelpox is very closely related, but is not regarded as the likely ancestor to smallpox, suggesting that the real reservoir remains at large or has gone extinct[2].
The researchers also discovered that smallpox virus evolved into two circulating strains, Variola major and Viriola minor, after English physician Edward Jenner developed a vaccine in 1796.

One form, Variola major, was highly virulent and deadly, the other Variola minor more benign. However, the two forms experienced a ‘major population bottleneck’ with the rise of immunization efforts.The date of the ancestor of the minor strain corresponds well with the Atlantic Slave trade which was likely responsible for partial worldwide dissemination.


This raises important questions about how a pathogen diversifies in the face of vaccination. While smallpox is now eradicated in humans, we should remain vigilant about its possible reemergence until we fully understand its origins.

[1] Duggan et al: 17th Century Variola Virus Reveals the Recent History of Smallpox in Current Biology – 2016. See here
[2] Smithson et al: Prediction of steps in the evolution of variola virus host range in PLoS One - 2014 

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