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Mummified remains yield oldest smallpox DNA known

This mummy was found in the same Lithuanian crypt where a team of researchers extracted DNA from a small child, thought to have died of smallpox.

Kiril achovskij

Like a time capsule with a secret message, the partially mummified remains of a child who lived in 17th-century Lithuania is shedding a surprising new light on one of humanity's most devastating killers.

In a report Thursday in the journal Current Biology, a team led by researchers at McMaster University in Hamilton says it has recovered by far the oldest complete DNA sequence of the smallpox virus, variola.

The find reveals the genetic makeup of the virus at a time that predates the advent of vaccination and suggests that the disease, at least in its deadliest form, may have emerged more recently than widely supposed.

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"The million-dollar question is when did smallpox jump into humans," said Hendrik Poinar, an evolutionary geneticist and a senior researcher on the project.

The new results do not completely answer the question, he said, but they point in an unexpected direction.

Until now, scholars have suspected that smallpox has been a scourge for millennia.

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This fits with historic accounts of outbreaks that seem to resemble the disease together with an observation made by British Egyptologists more than a century ago when the 3,000-year-old mummy of the pharaoh Ramesses V was partially unwrapped and said to exhibit pox-like marks on its withered skin.

The (non-viable) smallpox DNA retrieved from the Lithuanian specimen, which was discovered in a crypt beneath a church in Vilnius and dates back to between 1643 and 1665, tells a different story.

Prior to its discovery, all known strains of smallpox to have their DNA sequenced date from between 1944 and 1977, the year the last naturally occurring case was diagnosed. The disease was eradicated in 1979.

The lack of diversity in those 20th-century strains suggest that vaccination, introduced by Edward Jenner in 1796, had already driven most lineages of the disease to extinction.

The Lithuanian specimen is clearly different from the modern examples, yet not as different as would be expected from a disease that has supposedly existed and diversified in humans for many tens of centuries.

Based on the rate at which genetic mutations naturally accumulate in the virus, Dr. Poinar and his colleagues now calculate that the last common ancestor of all known strains must have been present in the late 1500s.

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Perhaps not uncoincidentally, mortality records show that pox does not become especially virulent until the mid-1600s, a time when major epidemics were raging throughout Europe and one that corresponds to the Lithuanian specimen. Together with the genetic data, this points to a fairly recent development in the character of smallpox and its relationship to humans.

The new evidence "asks us to rethink what the history might be if not the one we've always accepted," said Ann Carmichael, a historian of medicine and public health at Indiana University, who was not involved in the study.

Dr. Poinar sees two possible scenarios that explain the team's result.

The first is that smallpox only entered the human population in the 1500s, jumping across the species barrier from an unknown animal reservoir – which, disconcertingly, may still exist somewhere in the world.

The second is that smallpox evolved quietly in humans for a long period of time, but for an unknown reason become far more virulent some 400 years ago.

Either scenario suggests scientists have missed something important about a virus that was responsible for the deaths of hundreds of millions of individuals.

It also suggests that people today inhabit a more volatile and unpredictable viral environment than epidemiologists would like to imagine.

"Although there are important holes to fill in the historical record, the story is compelling," said Ian Lipkin, director of the Center for Infection and Immunity at Columbia University in New York. He added that the new study suggests that slave-trafficking is likely what brought the disease to the Americas.

Dr. Poinar said there are more potential specimens to be sampled and that the advent of technologies for retrieving and sequencing centuries-old DNA from viruses is likely to continue to change the established picture of the great epidemics that shaped human history.

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