Atahualpa, the last Incan emperor, was seized by troops in 1532 during the Spanish Conquest, but smallpox had already devastated the Inca Empire around 1524–1528.Credit: Florilegius/Alamy
More than 400 years ago, two people living in modern day Chile died while infected with the smallpox virus. Viral DNA found in their mummified remains has now yielded genetic evidence of when the disease arrived in the Americas.
The findings, published on 30 July in Science1, confirm that Orthopoxvirus variola — the virus that causes smallpox — arrived in the Americas from Europe. The study adds to a small but growing body of evidence that the smallpox virus lost genes as it adapted to human hosts, a mechanism that related viruses, such as the one that causes mpox, might also be using today.
“We don’t know anything about the recent history of viruses,” says Terry Jones, a computational virologist at Charité — University Medicine Berlin. Studies such as this provide a rare snapshot into a pathogen’s past, he says.
Surprise smallpox
Smallpox was one of the deadliest diseases in the world. The virus killed an estimated 300 million people in the twentieth century alone. Historical records suggest that its introduction into the Americas was similarly catastrophic, killing millions of people across two continents.
However, viruses don’t leave much archaeological evidence. So far, there are only two examples of smallpox DNA from before the twentieth century: a set of sequences from seventh-century Viking remains, and a single sequence from a seventeenth-century Lithuanian mummy.
What limited genetic evidence researchers do have suggests that smallpox has undergone intense evolution over the centuries. The seventh-century virus genome is much larger and contains more active genes than do twentieth-century smallpox strains.
Smallpox and other viruses plagued humans much earlier than suspected
This latest study found smallpox by accident. The team was originally testing DNA analysis software as a way to study the human history of an archaeological site in northern Chile. To do this, researchers had sequenced DNA from the remains of two people who lived in a small settlement some time between 1492 and 1631.
To their surprise, the analysis also uncovered traces of an unknown smallpox variant. Finding traces of the disease “didn’t cross my mind”, says co-author Constanza de la Fuente Castro, a biological anthropologist at the University of Chile in Santiago. But that “makes it even more exciting”.
The team then compared the variant to other ancient and modern smallpox genomes. What they found suggested that the Chilean variant split off from a European branch of the disease around the thirteenth century, confirming that European colonizers were the source of smallpox in the region.
