An international team of researchers has identified the oldest known sample of the variola virus that causes smallpox in the mummified remains of a 17th-century child.
The findings, published in the journal Current Biology, raise new questions about the history of the pathogen, suggesting that smallpox, once thought to be an ancient disease, may have in fact emerged in rather recent times.
Smallpox remains the only human disease eradicated by vaccination - it was also the first disease to be combated with a vaccine when one was developed in 1796.
However, the history of this pathogen that caused millions of deaths worldwide remains mysterious.
"Scientists don't yet fully comprehend where smallpox came from and when it jumped into humans," said evolutionary geneticist Hendrik Poinar, director of the McMaster Ancient DNA Center and a researcher with Michael G. DeGroote Institute of Infectious Disease Research.
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The disease had long been thought to have appeared in human populations thousands of years ago. Some researchers even diagnosed the pharaoh Ramses V with smallpox on the basis of visible pustular rashes and scars.
They may have been wrong, the study suggests.
New clues on the evolutionary history of the devastating viral disease came from the partial mummified remains of a child of undetermined sex. The mummy was found with no coffin or associated artifacts in the crypt of the Dominican Church of the Holy Spirit of Vilnius, Lithuania.
Once scheduled to be buried, the remains are now part of a project created in 2011 by anthropologist Dario Piombino-Mascali to study all the mummies in Lithuania, from the Egyptian mummies in the local museums, to the remains from the Holy Spirit crypt and 20th-century anatomical preparations.
"Those mummies revealed a number of diseases, such as arteriosclerosis, tuberculosis and bone pathologies. But this case has been really surprising," Piombino-Mascali, at the department of anatomy, histology, and anthropology of Vilnius University, told Seeker.
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According to the researchers, the child died between the ages of 2 and 4 and in the years between 1643 and 1665, close to the time of several documented European epidemics.
Heavily fragmented DNA was extracted from the mummy's skin so the researchers were able to capture, sequence and reconstruct the complete genome of an ancient strain of variola virus. There was no indication of a live virus in the sample, so the mummy was not infectious.
"We believe this is the oldest smallpox genome sequenced to date," Ana Duggan, a postdoctoral fellow at the McMaster University Ancient DNA Center in Canada, told Seeker.
Duggan and colleagues compared the 17th-century strain to versions of the variola virus genome dating from 1946 up to 1977. The disease was declared eradicated by the World Health Organization in 1980.
"The results showed a very recent common ancestor for all available 20th-century variola strains and our 17th-century strain," Duggan said.
Indeed, the common viral ancestor originated sometime between 1588 and 1645, a date corresponding to a period of exploration, migration and colonization that would have helped the viral dissemination of smallpox around the globe.
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"So now that we have a timeline, we have to ask whether the earlier documented historical evidence of smallpox, which goes back to Ramses V and includes everything up to the 1500s, is real," co-author Hendrik Poinar, the director of the Ancient DNA Center at McMaster University in Canada, said.
He wondered whether cases such as that of Ramses V are misidentifications.
"It is likely possible to mistake smallpox for chicken pox and measles," Poinar said.
The researchers were also able to identify distinct periods of viral evolution and discovered that the split between two versions of the disease - the highly virulent and deadly variola major and the much more benign variola minor - occurred in the late 18th century.
Since the change occurred very close to the time English physician Edward Jenner famously developed a vaccine in 1796, it is possible that vaccination triggered the virus to split into two strains.
"This raises important questions about how a pathogen diversifies in the face of vaccination. While smallpox was eradicated in human populations, we can't become lazy or apathetic about its evolution until we fully understand its origins," Duggan said.
Photo: A mummy found in the same Lithuanian crypt where researchers extracted DNA from a small child, thought to have died of smallpox. Credit: Kiril Čachovskij WATCH: How Scientists Are Hacking Bacteria to Fight Disease