Genetic research suggests that smallpox, a pathogen that caused millions of deaths worldwide, may not be an ancient disease but a more modern killer that went on to become the first human disease eradicated by vaccination.

The findings, published in the journal Current Biology, raise questions about the role smallpox may have played in human history and fuel a debate over when the virus that causes smallpox, variola, first emerged and evolved in response to inoculation and vaccination.

Ana Duggan, a post-doctoral fellow in the McMaster Ancient DNA Centre.Ana Duggan, a post-doctoral fellow in the McMaster Ancient DNA Centre.Smallpox had long been thought to have appeared in human populations thousands of years ago in Egypt, India and China.

In an effort to better understand its evolutionary history, and after obtaining clearance from the World Health Organization in Geneva, scientists extracted DNA from the remains of a Lithuanian child believed to have died between 1643 and 1665, a period during which several smallpox outbreaks were documented.

The smallpox DNA was captured, sequenced, and the genome was reconstructed. There was no indication of live virus in the sample and so the mummies are not infectious.

Researchers compared and contrasted the 17th Century strain to those from a modern databank of samples dating from 1940 up to its eradication in 1977. The work shows that the evolution of smallpox virus occurred more recently than previously thought, with all the available strains of the virus having an ancestor no older than 1580.

The pox viral strains that represent the true reservoir for human smallpox remains currently unsampled. Both the closest gerbil (Tetarapox) and camel pox are distantly related and so are not the likely ancestors to smallpox. Researchers say this suggests that the real reservoir remains at large or has gone extinct.

Researchers also discovered that smallpox virus evolved into two circulating strains, variola major and minor, after English physician Edward Jenner famously developed a vaccine in 1796.

One form of VARV (Variola virus), known as V. major was highly virulent and deadly. The other V, minor was more benign. However, scientists say, the two forms experienced a “major population bottleneck” with the rise of global 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.

The World Health Organization declared smallpox eradicated in 1980.

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