Viking Age Smallpox Complicates Viral Evolution Story

The evolution of the deadliest virus in human history, smallpox, is only partially understood. Like the new coronavirus and many other disease-causing viruses, smallpox appears to have originated from animals, probably rodents, and has spread to humans, probably thousands of years ago. In the 20th century alone, it killed hundreds of millions of people.

Until now, the first confirmed case of smallpox had been found in the mummified remains of a 17th-century Lithuanian boy. On Thursday, an international team of researchers delayed that date 1,000 years, reporting in the journal Science that they had recovered smallpox DNA from the remains of people in northern Europe in the Viking era.

The virus they found is now extinct and has not been found on other more recent skeletal remains. It is not an ancestor of the modern smallpox virus, but an evolutionary dead end. It has more genes than the modern virus, and scientists have observed that among the many different smallpox viruses in nature, fewer genes tend to mean a more deadly virus. Putting that data together, a leading smallpox specialist suggested that the modern virus could have become more deadly as it evolved. Most viruses become less deadly over time.

Smallpox viruses are not closely related to coronaviruses, and the research has no direct application to the current spread of the new coronavirus. But in the midst of a pandemic, even the idea of ​​some viruses evolving to be more deadly is decidedly awkward.

The early date of the new smallpox virus, experts say, is significant but not surprising. Like other smallpox virus experts, the authors think that while DNA evidence is so sparse, smallpox almost certainly goes much further back in time.

Terry C. Jones, who studies the evolution of disease-causing organisms at Cambridge University and was one of the lead authors, said that judging from historical sources, “it seems quite likely that the virus was present in, say, India, or maybe China, 1,000 or 1,500 years before the Common Era. “

Dr. Jones said the most intriguing finding was the genetic makeup of the smallpox virus recovered from the bones of 11 people who lived between 600 and 1050, and the fact that the ancient viral strain is now extinct. The modern version, as the authors call it, was eradicated from the human population in 1980.

The Latin name for the smallpox virus is Variola, and other strains of Variola are known. Variola minor, which was eradicated along with smallpox (Variola major), caused a mild illness with a mortality rate of less than 1 percent, while smallpox killed approximately 30 percent of infected people. Why it was less lethal is unknown.

The differences in the Viking variant are significant enough for the virus to form a new group, or clade, of Variola. It is not an older version of the modern virus. Both modern smallpox and the newly discovered variant descended from a common ancestor, but diverged at least 1,700 years ago. Dr. Jones said: “Viking viruses were on a different evolutionary path that could not have led to modern viruses.”

Klaus Osterrieder, a smallpox virus specialist at Hong Kong City University and who was not part of the research, said the Viking virus analysis and the establishment of a new clade was quite convincing.

The genetic details of the Viking virus are what sparked speculation that the smallpox virus may have become more deadly. Barbara Mühlemann, Also a Cambridge virologist and the first author of the article, said that the general understanding of smallpox viruses is that those with the fewest genes aimed at tricking a host’s immune system are actually more deadly. The reason is not clear, although with viral infections, a very strong immune reaction is often what kills the victim.

“The pattern we have seen in the document,” he said, “is that there has been a loss of genes over time” in the modern smallpox virus compared to the Viking virus, which had more active genes than the modern virus. But, she warned, she and her colleagues have no direct evidence that the Viking version of the virus was less deadly.

Antonio Alcami, a smallpox specialist at the Autonomous University of Madrid, wrote a comment in the same issue of Science, hypothesizing that smallpox actually evolved to become more deadly.

He said the standard view of viral evolution, in which viruses become less virulent, may not always be true. The Variola virus evolved in humans over time. “Maybe it was a mild illness for a time,” he said.

That idea has been previously suggested, Dr. Jones said, by historians who proposed that smallpox may have been a relatively benign disease.

The way this kind of evolution could have happened is “counterintuitive,” said Dr. Alcami. Genes that are inactivated in modern smallpox and other deadly smallpox viruses are those that help weaken or evade the immune responses of the infected host. But why lose those genes, since they should help a virus?

Somehow, the loss of those genes seems to help the virus, Dr. Alcami said. Perhaps with fewer active genes, the virus can replicate faster and thus improve its chances of transmission to another person, despite the fact that it is causing an out-of-control immune reaction, which, in the end, is what kills the Guest. He emphasized that he was posing the idea only as a hypothesis to promote discussion and further investigation.

Dr. Osterrieder said that while the idea was still speculative, he thought it made sense. “I think it is a very compelling hypothesis,” he said.