Smallpox may be more modern disease, not ancient, as long thought: researchers

TORONTO — It’s long been thought that smallpox is an ancient infectious disease that began decimating human populations thousands of years ago, but new genetic research is casting doubt on that belief, suggesting the pathogen may have been a much more modern scourge.

Smallpox, caused by the variola virus, was officially declared eradicated through vaccination by the World Health Organization in 1980 following the last known case in Somalia three years earlier. Before its disappearance, smallpox was among humankind’s most feared diseases, killing an estimated 300 million to 500 million people worldwide in the 20th century alone.

But a long-standing debate has surrounded the virus: just how far back in our history did it emerge? And from where did it come?

“Scientists don’t yet fully comprehend where smallpox came from and when it jumped into humans,” said Hendrik Poinar, an evolutionary geneticist at McMaster University and senior author of a study that examined the pathogen’s genetic lineage. 

“This research raises some interesting possibilities about our perception and age of the disease.”

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Based in part on historical accounts, it’s been generally accepted that smallpox was an affliction suffered by ancient civilizations in India and China, but also in Egypt, where the pock-marked mummified remains of Ramses V led to the belief that the 12th-century BC pharaoh had suffered from and may have died from the disease.

But the discovery of the variola virus in far more recent mummified remains — those of a young Lithuanian boy who died in the mid-1600s, when a number of smallpox outbreaks ravaged populations across Europe — is challenging those notions.

That’s because scientists were able to reconstruct the variola genome from DNA extracted from the naturally mummified remains of the child, allowing them to compare the genetic signature of the 17th-century strain with that of a more contemporary strain dating from 1940 to 1977, when the world’s last case of smallpox occurred.

Although the remains found in a crypt in the capital city, Vilnius, posed no risk because there was no live variola present, the researchers had to get permission from the WHO to proceed because of concerns over the smallpox virus potentially being used as a biological weapon, for which there is no cure or treatment.

Samples of the deadly virus are now known to exist in only two locations in the world: high-containment labs in Russia and the U.S. Vaccine is still stockpiled in the event the fast-spreading pathogen either escapes or is somehow resurrected.

In a paper published Thursday in the journal Current Biology, scientists at McMaster, the University of Vilnius and collaborators at several other research institutions concluded that the genetic evolution of the smallpox virus occurred far more recently than previously thought.

“We think the ancestor of our Vilnius strain and the contemporary strain is somewhere in the order of 1580,” said Poinar, director of McMaster’s Ancient DNA Centre, who has also helped trace the genetic evolution of the bacteria that causes bubonic plague and sequenced the genome of the extinct woolly mammoth.  

“And it immediately poses this problem as to, well, 1580. But what about Ramses V and what about all these other purported cases?

“I have my thoughts on those and these may not be right. There’s two possibilities, and one is those just weren’t pox — and (that) shows the problem with retrospective diagnoses,” he said, adding that the other possibility is that another disease existed at the time that also caused disfiguring pox-like symptoms.

Poinar said the smallpox virus, which infects only humans, evolved into two circulating strains after 1796, when English physician Edward Jenner developed a vaccine to prevent infection.

One form, known as V. major, was highly virulent, with a 30 to 50 per cent mortality rate. The other, V. minor, was much more benign. The date of the ancestor of the minor strain corresponds with the African slave trade, which was likely partially responsible for worldwide dissemination of the disease during the period.

“This raises important questions about how a pathogen diversifies in the face of vaccination,” said Ana Duggan, a post-doctoral fellow in Poinar’s lab who did the computational work to reconstruct the genome of the virus from the Vilnius remains.

“We know remarkably little about this disease that has this fantastic history of being the first and thus far only human disease that was eradicated by vaccination — because it was so feared,” she said from Hamilton.

And although smallpox now has been eradicated, “we can’t become lazy or apathetic about its evolution —and possible re-emergence — until we fully understand its origins.”

Poinar agreed that the smallpox virus would make a “scary biological weapon” because of the speed at which it can pass from one person to another, especially in crowds.

“It’s definitely one on the radar for most countries,” he said. “The question is how quick can you come up with a vaccination campaign?

“So understanding its origins and its evolutionary history are critical to control and eradication should it come back.”

– Follow @SherylUbelacker on Twitter.

Sheryl Ubelacker, The Canadian Press

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