Ancient DNA from Chilean mummies offers the firmest evidence yet that European colonization introduced smallpox to the Americas.

Before its eradication in 1980, largely due to vaccination, smallpox stood as one of humanity's deadliest diseases. It historically claimed the lives of about one-third of those infected, often leaving survivors with deep, disfiguring scars.

While outbreaks ravaged Asia and Europe, the virus eventually reached the Americas. Colonial writings and missionary reports extensively documented its catastrophic impact, killing millions and decimating Indigenous populations who lacked prior exposure.

The new scientific evidence comes from an analysis of Chilean mummies, which provides the strongest genetic link yet to the virus as it existed outside the Americas. This offers a clearer understanding of how smallpox reached remote populations through colonization, explained geneticist Shigeki Nakagome of Trinity College Dublin.

In the new study, Nakagome and colleagues examined 13 bone samples previously collected from an archaeological site at Camarones, in northern Chile.

Researchers found evidence of two smallpox infections in ancient DNA from the leg bone fragments of an adult man and woman.

From dating the remains and peeking at the genes, scientists concluded the two likely died between 1492 and 1631. Scientists also compared the genes in this version of smallpox to other versions and fit it neatly between European strains from medieval times and later versions. This was important molecular evidence, suggesting that the strains of smallpox infecting people in the Americas evolved first from Europe.

“Nobody would ever question that smallpox came to this hemisphere from colonization, but this proves it,” said Patricia Foster, a biologist at Indiana University. She had no role in the new research, which was published Thursday in the journal Science.

Exactly which population brought smallpox to the Americas from the Old World remains unclear, said the study authors. European settlers came in different waves to the Americas following the explorations of Christopher Columbus in the Caribbean in 1492 and Amerigo Vespucci along the South American coast about a decade later. The disease also could have passed through Africa as part of the introduction and expansion of the slave trade.

These smallpox infections in South America were identified in an area with no previous record of the disease, opening new questions about how the virus got so far south — possibly spreading along Indigenous trading networks that had long pre-existed the arrival of Europeans.

Studying various strains of the virus also allowed scientists to pinpoint how it evolved, turning off certain genes to become more effective at its deadly mission.

In addition to confirming the history of smallpox, the research also shines a light on the human cost. The two sick individuals studied were between 18 and 35 years old, and the disease is likely what killed them.

The findings point to how devastating the disease was across the Americas, wiping out entire populations and leaving them vulnerable to European conquest, said study coauthor Constanza de la Fuente Castro, a biological anthropologist at the University of Chile.

“It wasn't just cultural or demographic. It's literally written into biological evidence that we can still recover and read today,” de la Fuente Castro said.