New study on the evolution of the smallpox virus published in Science*
The smallpox virus circulated in northern Europe as early as the seventh century. Evidence for this was found in DNA fragments obtained from Viking skeletons and analyzed by Researchers from Charité – Universitätsmedizin Berlin, the University of Cambridge, and the University of Copenhagen. This is the first time researchers have produced scientific proof that the smallpox virus has been infecting humans for at least 1,400 years. The unexpected level of genetic diversity displayed by the virus may also be of relevance in the future.
The variola virus, which causes smallpox, is usually considered the deadliest virus in the world. During the twentieth century alone, the virus, which has a mortality of up to 30 percent, claimed an estimated 300 to 500 million lives. Following a global vaccination program, the human smallpox virus was declared eradicated in 1980. Even today, however, Central and West Africa sees cases of monkeypox, a disease which occurs when a close relative of the smallpox virus is transmitted from animals to humans. Monkeypox produces similar symptoms to true smallpox but has a lower mortality rate.
One question which has remained unanswered is just how long the human smallpox virus had been circulating prior to its eradication. Historical documents suggest that smallpox may have existed more than 3,000 years ago. However, the oldest skeleton in which the virus had previously been identified was only around 360 years old. “We effectively had a discrepancy of almost 3,000 years between what we had surmised about the history of the smallpox virus and what we actually know,” explains the bioinformatics expert Dr. Terry Jones, Research Group Leader at Charité’s Institute of Virology on Campus Charité Mitte, and joint research lead of the study, alongside colleagues from the University of Copenhagen’s Lundbeck Foundation GeoGenetics Centre and the University of Cambridge. “Using modern molecular biology techniques, we set out to find scientific evidence that would corroborate written records indicating an earlier presence of smallpox,” says Dr. Jones. Their approach proved successful. The researchers discovered the variola virus in up to 1,400-year-old skeletal remains from Viking burial sites in Denmark, Norway, Sweden, Russia, and England.
For their analysis, the researchers studied the DNA of almost 1,900 skeletons, between 150 and 30,000 years old, which had been found at various sites across Europe and America. In 13 cases, the researchers managed to isolate fragments of DNA from teeth and/or sections of the temporal bone. The age and authenticity of the DNA samples was confirmed by the presence of specific DNA damage which is associated with age-related degradation. Eleven of these individuals lived between approximately 600 and 1050 AD, i.e. during the Viking Age (793 to 1066 AD). “Ours is therefore the first study to provide molecular biology-based evidence that even Vikings were infected with the smallpox virus,” says the article’s first author, Dr. Barbara Mühlemann, a researcher from the German Center for Infection Research (DZIF) at Charité’s Institute of Virology on Campus Charité Mitte. “We were therefore able to reduce the current discrepancy between historical anecdotes and direct evidence of smallpox by approximately 1,000 years. However, we consider it likely that infections occurred much earlier than that.”
The new research findings contradict a range of previous assumptions which posited that the smallpox virus was first introduced into Europe by, for example, returning crusaders between the eleventh and thirteenth centuries. Summarizing their findings, Dr. Jones, who is both a DZIF researcher and a Senior Research Associate at the University of Cambridge, says that: “Based on these recently confirmed smallpox cases in northern Europe and the historical reports of suspected cases in southern and western Europe, we assume that the smallpox virus must have been circulating widely within Europe from at least the end of the Viking Age.”
Some of the samples were so well preserved that the researchers were able to use computers to reconstruct the complete viral genome sequence from the extracted fragments. Their sequence analysis revealed that the smallpox virus which was in circulation during the Viking Age differs significantly from the variola virus of the twentieth century, and that it shares more similarities with the poxvirus strains found in camels and gerbils. The ancient virus displayed a very different pattern of active and inactive genes. “Some of these genes determine, among other things, the degree of specificity which the smallpox virus shows for its host,” explains Dr. Mühlemann. She adds: “Judging by the activity pattern of the Viking Age smallpox virus, it is possible that, at the time, the virus was not only capable of infecting humans but animals as well.” It is, however, impossible to deduce either the mortality rate of the ancient virus or the nature of the symptoms it might have produced – even if the researchers’ genetic data suggest that the virus may have caused a fever in its Viking Age hosts.
“We did not expect this degree of genetic diversity in the human smallpox virus. It really did take us by surprise,” says Dr. Jones. “The evolution of the smallpox virus is clearly more complex than we had assumed. The history of the human smallpox virus shows that it followed very diverse genetic paths. Given this history, it is feasible that other poxviruses, currently circulating in animals, could have had similarly diverse evolution – and this could have consequences for the transmission of the disease from animals to humans. In the future, we should therefore keep a closer eye on animal poxviruses.”
*Mühlemann B et al. Diverse variola virus (smallpox) strains were widespread in northern Europe in the Viking Age. Science. 2020 Jul 24. doi: 10.1126/science.aaw8977
On this study
Dr. Jones co-led the study with Prof. Dr. Eske Willerslev (St. John’s College, University of Cambridge; The Lundbeck Foundation GeoGenetics Centre at the University of Copenhagen and the University of Cambridge) and Prof. Dr. Martin Sikora (The Lundbeck Foundation GeoGenetics Centre at the University of Copenhagen). Dr. Mühlemann shares co-first authorship with Dr. Lasse Vinner (The Lundbeck Foundation GeoGenetics Centre at the University of Copenhagen). Dr. Mühlemann’s contributions to the project were made as part of her PhD at the University of Cambridge and as a postdoctoral researcher on Dr. Jones’ team at Charité. The study forms part of a long-term project by the Lundbeck Foundation GeoGenetics Centre which aims to sequence 5,000 ancient human genomes.
True smallpox is a disease caused by the variola virus and is transmitted via infective droplets. Typical symptoms include fever and blisters on the skin. The disease has a mortality rate of up to 30%. In many survivors, the characteristic skin eruptions leave life-long scarring. The disease can also result in hearing loss or blindness.
Lundbeck Foundation GeoGenetics Centre
Charité – Universitätsmedizin Berlin
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