Smallpox virus found in a child’s mummy changes our view of the history of the killer disease

An international group of researchers has managed to isolate the genetic material of the smallpox virus from the mummy of a Lithuanian child who died in the 17th century, and the genome of the virus has now been sequenced. These results raise new questions regarding the role smallpox has played in the history of the human race.

Smallpox is among the most destructive illnesses in the history of humanity, and the first, and so far the only, contagious disease which has been completely eradicated through vaccines. The history of the disease has been claimed to reach back millennia, into ancient Egypt, India and China, while other studies have suggested that the variola virus (VARV) which causes smallpox emerged much later.

A new study by an international group of researchers, published in Current Biology, supports the hypothesis that smallpox is a relatively recent killer which has mainly evolved during recorded history, not thousands of years ago.

Researchers discovered DNA of the smallpox virus in the remains of a child who died in the 17th century. The child was one of several mummified corpses found in the crypt of the Church of the Holy Spirit in Vilnius.

The DNA of the virus was badly fragmented, but the researchers succeeded in reconstructing an entire smallpox virus. “This is the oldest smallpox virus on which we have been able to conduct genome sequencing,” explains postdoctoral researcher Maria Perdomo from the University of Helsinki, who conducted most of the analyses on the samples. The analysis was carried out in the Ancient DNA research facility at McMaster University in Ontario, Canada.

According to professors Klaus Hedman and Antti Sajantila, the discovery of smallpox DNA first worried the researchers.

“Had we found a live, virulent virus, we would have immediately halted the study. However, the virus genomes were very fragmented, and there is no risk of infection. The WHO gave us clearance to proceed with the study, so we were able to further investigate the evolutionary history of the smallpox virus.”

When the researchers compared the genome of the virus found in the child mummy with the smallpox strains from 1940–1977 stored in databanks, they found a surprising fact: the shared ancestral form of all known smallpox viruses is from approximately 1580. “In light of this discovery, it is possible that the variola virus is a relatively recent killer and not, as has been thought, the reason for the death of Pharaoh Ramesses V in 1145 BCE,” state the researchers.

According to Professor Hendrik Poinar, evolutionary geneticist who leads the Ancient DNA Centre at McMaster University, the new results provide new interesting perspectives for the discussion on the age and origin of the smallpox virus as well as its role in the history of humanity.

VIRUS VERSUS VACCINATION

The fight against smallpox in the Western world began at the turn of the 19th century with the vaccine developed by Edward Jenner. In Finland, the first extensive vaccination efforts took place in 1802. Researchers have been interested in how a pathogen such as the smallpox virus reacted to its diminishing habitat due to vaccinations.

The results indicate that after inoculations began, the smallpox virus evolved into two parallel strains. Of these, Variola major is the more virulent, and is associated with a death rate of around thirty per cent. Meanwhile, approximately one in every hundred people to contract Variola minor died. On the other hand, since V minor was less homicidal than its cousin, it was more efficiently transmitted through the population. The global spread of V minor seems to have been further boosted by the transatlantic slave trade. In the early 20th century, V minor had become the dominant strain of smallpox.

In 1980, the WHO declared smallpox eradicated from the globe.

The study was published in Current Biology on 8 December 2016, and involved researchers from Finland, Canada, Lithuania, Australia, the United States, England and France.

More information:

Professor Klaus Hedman, puh. +358 50 4482801, klaus.hedman@helsinki.fi
Professor Antti Sajantila, puh. +358 400 605205, antti.sajantila@helsinki.fi
Postdoctoral Researcher Maria Perdomo, puh. +358 50 4482846, maria.perdomo@helsinki.fi

Reference: Ana T. Duggan, Maria F. Perdomo, Dario Piombino-Mascali, Stephanie Marciniak, Debi Poinar, Matthew V. Emery, Jan P. Buchmann, Sebastian Duchéne, Rimantas Jankauskas, Margaret Humphreys, G. Brian Golding, John Southon, Alison Devault, Jean-Marie Rouillard, Jason W. Sahl, Olivier Dutour, Klaus Hedman, Antti Sajantila, Geoffrey L. Smith, Edward C. Holmes, and Hendrik N. Poinar: 17th Century Variola Virus Reveals the Recent History of Smallpox. Current Biology. 8th Dec, 2016. http://dx.doi.org/10.1016/j.cub.2016.10.061
Archaeovirology - a journey to the past

In addition to smallpox, the corpses in the crypt of the Church of the Holy Spirit yielded other human viruses, and there is a great deal of data to analyse. Dario Piombino-Mascali, who specialises in the study of human mummies at the University of Vilnius, believes that research will uncover many highly interesting findings.

“We should be grateful to these unnamed dead people, who are telling their stories from centuries past,” he says.

The University of Helsinki researchers describe archaeovirology as a time machine which offers glimpses into a different world, far in humanity's past.

“Our modern methods may unearth hitherto unknown pathogens from our past, perhaps ones that disappeared millennia ago. This means completely new kind of information on why viruses are born, how they develop, what kinds of environments they need to remain vital and what kinds will destroy them.“ Has there ever been a virus so deadly that it has dragged entire villages or even nations into the grave?”

“Perhaps one day we will be able to compare the viruses in Homo sapiens and Homo neanderthalensis,” says an optimistic Professor Hedman.

What benefit is there in studying ancient viruses? Is there business potential here?

“This is groundbreaking basic research that goes to the very origins of information. We don’t yet know what it is possible to discover through our work, and what the benefit from our discoveries will be,” replies Professor Sajantila.

“In the 1960s, President Kennedy was asked why he wanted to study space and try to get to the Moon," Hedman points out.