An international team of scientists has discovered extinct strains of smallpox in the teeth of Viking skeletons from sites across northern Europe, and reconstructed near-complete genomes of the causative variola virus (VARV) from multiple samples. Their findings, published in Science, are reported just days after an independent team of scientists published details of a study through which they identified smallpox virus strains that were circulating during the American Civil War.

The investigators reporting on the latest Viking discoveries say the smallpox virus samples found in the teeth predate the earliest confirmed smallpox cases by about 1000 years and prove for the first time that the killer disease plagued humanity for at least 1400 years. “We discovered new strains of smallpox in the teeth of Viking skeletons and found their genetic structure is different to the modern smallpox virus eradicated in the 20th century,” said study leader Eske Willerslev, PhD, at St John’s College, University of Cambridge, who is director of the Lundbeck Foundation GeoGenetics Centre, University of Copenhagen. “The 1400-year-old genetic information extracted from these skeletons is hugely significant because it teaches us about the evolutionary history of the variola virus that caused smallpox. We already knew Vikings were moving around Europe and beyond, and we now know they had smallpox. People traveling around the world quickly spread COVID-19 and it is likely Vikings spread smallpox. Just back then, they traveled by ship rather than by plane.

Willerslev and colleagues reported on their discoveries in a paper titled, “Diverse variola virus (smallpox) strains were widespread in northern Europe in the Viking Age.”
Smallpox killed around a third of people it infected, leaving another third permanently scarred or blind. The disease is estimated to have caused 300–500 million deaths in the 20th century alone, until it was officially declared eradicated by the World Health Organization in 1980. The World Health Organization launched an eradication program in 1967 that included contact tracing and mass communication campaigns—all public health techniques that countries have been using to control today’s coronavirus pandemic. In fact, smallpox was eliminated throughout most of Europe and the United States by the beginning of the 20th century, but it remained endemic throughout Africa, Asia, and South America. It was the global rollout of a vaccine that ultimately stopped smallpox in its tracks.

Smallpox is the first human disease to be wiped out, although the virus is stored in certain laboratories in the United States and Russia. Nevertheless, there are still concerns that smallpox-like disease might emerge again, the authors noted, “… via accidental or deliberate reintroduction of variola virus, adaptation of monkeypox virus to humans, or zoonosis, or genetic engineering of another orthopoxvirus.” Knowing more about the evolutionary history of variola virus would, therefore, be of particular interest to scientists, they pointed out.

Historians believe smallpox may have existed since 10,000 BC but until now there was no scientific proof that the virus was present before the 17th century. “The timeline of the emergence of smallpox in humans is unclear,” the team wrote. “Hypotheses regarding the earliest history of VARV have been derived exclusively from often ambiguous historical accounts and from the visual examination of mummies dating from as early as 3570 ya.” And while it is not known how the virus first infected humans, it is, like COVID-19, believed to have come from animals.

The researchers found smallpox in skeletons from 11 Viking-era burial sites in Denmark, Norway, Russia, and the U.K. They also found it in multiple human remains from Öland, an island off the east coast of Sweden with a long history of trade. The team was able to reconstruct near-complete variola virus genomes for four of the samples. The sequences revealed now extinct relatives to the modern variola viruses that were in circulation before smallpox eradication. “We date the most recent common ancestor of variola virus to ~1700 years ago,” the authors noted. “Distinct patterns of gene inactivation in the four near-complete sequences show that different evolutionary paths of genotypic host adaptation resulted in variola viruses that circulated widely among humans … Our finding of the virus in northern Europe at these times disproves various suggestions of first introductions involving later dates.”

Senior study author Martin Sikora, PhD, from the Centre for GeoGenetics, University of Copenhagen, explained, “The timeline of the emergence of smallpox has always been unclear but by sequencing the earliest-known strain of the killer virus, we have proved for the first time that smallpox existed during the Viking Age. While we don’t know for sure if these strains of smallpox were fatal and caused the death of the Vikings we sampled, they certainly died with smallpox in their bloodstream for us to be able to detect it up to 1400 years later. It is also highly probable there were epidemics earlier than our findings that scientists have yet to discover DNA evidence of.”

The team claims that their discoveries of Viking Age variola virus sequences push back the definitive date of the earliest variola infection in humans by about 1000 years. Terry Jones, PhD, one of the senior authors leading the study, is a computational biologist based at the Institute of Virology at Charité—Universitätsmedizin Berlin and the Centre for Pathogen Evolution at the University of Cambridge. He commented, “There are many mysteries around poxviruses. To find smallpox so genetically different in Vikings is truly remarkable. No one expected that these smallpox strains existed. It has long been believed that smallpox was in Western and Southern Europe regularly by 600 AD, around the beginning of our samples.”

It’s previously been thought that returning crusaders or other later events may have brought smallpox to Europe, but the new discoveries overturn such theories, he continued. “We have proved that smallpox was also widespread in Northern Europe … While written accounts of disease are often ambiguous, our findings push the date of the confirmed existence of smallpox back by a thousand years.

”Virologist and co-first author Lasse Vinner, PhD, at the Lundbeck Foundation GeoGenetics Centre, suggested that an understanding of the genetic structure of the ancient smallpox virus will potentially help scientists understand viral evolution and so add to the bank of knowledge that helps in the fight against emerging viral diseases. “The early version of smallpox was genetically closer in the pox family tree to animal poxviruses such as camelpox and taterapox, from gerbils,” Vinner said. “It does not exactly resemble modern smallpox which shows that the virus evolved. We don’t know how the disease manifested itself in the Viking Age—it may have been different from those of the virulent modern strain which killed and disfigured hundreds of millions.”

Computational biologist and co-first author Barbara Mühlemann, PhD, took part in the research during her PhD at the Centre for Pathogen Evolution at the University of Cambridge. Now also based at the Institute of Virology at Charité, she commented, “The ancient strains of smallpox have a very different pattern of active and inactive genes compared to the modern virus. There are multiple ways viruses may diverge and mutate into milder or more dangerous strains. This is a significant insight into the steps the variola virus took in the course of its evolution.

“Knowledge from the past can protect us in the present, Jones maintained. “When an animal or plant goes extinct, it isn’t coming back. But mutations can re-occur or revert and viruses can mutate or spill over from the animal reservoir so there will always be another zoonosis.” As Willerslev concluded, “Smallpox was eradicated but another strain could spill over from the animal reservoir tomorrow. What we know in 2020 about viruses and pathogens that affect humans today, is just a small snapshot of what has plagued humans historically.”

The reported research is part of a long-term project to sequencing 5000 ancient human genomes and their associated pathogens, through a collaboration between the Lundbeck Foundation, the Wellcome Trust, the Nordic Foundation, and Illumina.