Ancient DNA from two Indigenous individuals who lived in northern Chile between 1492 and 1631 places the virus that devastated the Americas on a path from medieval Europe toward modern smallpox.
When Europeans arrived in the Americas, they brought diseases that Indigenous populations had never encountered. Smallpox was among the deadliest. Epidemics swept through communities from Mexico to the Andes, killing an estimated three to four million people and helping to reshape the political landscape of two continents. Yet the virus responsible has left little direct trace from that era.
A study published in Science now offers a genetic look at smallpox from the early colonial Americas. Bruno González and colleagues recovered ancient smallpox DNA from two mummified Indigenous individuals from northern Chile who lived between 1492 and 1631 CE, the period spanning the late Inca Empire and the early Spanish colonial era. The genome they reconstructed is the earliest known smallpox genome from the Americas.
A virus that shaped history
Smallpox was caused by the variola virus, a member of the poxvirus family. It spread from person to person, causing fever and a characteristic rash of fluid-filled pustules, and killed roughly 30 percent of those infected with its most common form. Survivors were often left scarred and sometimes blind.
The disease afflicted humanity for millennia before a global vaccination campaign led by the World Health Organization eradicated it. The last natural case occurred in Somalia in 1977, and the World Health Assembly declared smallpox eradicated in 1980. It remains the only human disease to have been wiped out.
Because smallpox is gone, scientists studying its history depend on samples preserved in collections and, increasingly, on ancient DNA from human remains. Earlier ancient-DNA studies recovered variola genomes from Viking Age skeletons in northern Europe, revealing that the virus was circulating more than a thousand years ago in lineages different from those of the twentieth century. But the history of the virus in the Americas has remained largely unknown at the genetic level.
Finding the virus in mummified remains
The dry conditions of northern Chile, home to the Atacama Desert, one of the driest places on Earth, are known for preserving human remains exceptionally well. The region is also home to the Chinchorro mummies, some of the oldest intentionally mummified bodies in the world.
Working with such remains, the researchers identified fragments of smallpox DNA and pieced them together into a genome. They named the viral lineage CAM9.
Placing CAM9 on the variola family tree, the team found that it sits between early medieval European strains and the lineages that ultimately gave rise to modern smallpox. In other words, the virus that infected these individuals represents an intermediate stage in the evolution of variola, consistent with its arrival in the Americas through European colonization.
What the genome adds
Written accounts from the sixteenth century describe waves of epidemic disease following the arrival of Europeans, and historians have long linked these to smallpox, measles and other infections. But historical descriptions of symptoms can be ambiguous, and they say nothing about which strains of a virus were responsible or how they were related to one another.
A viral genome offers a different kind of evidence. It can help confirm the presence of a particular pathogen, and it can show how the strains circulating in the colonial Americas fit into the broader evolutionary history of the disease. The CAM9 genome fills a gap between the medieval European viruses and the more recent strains collected before eradication.
The finding also helps calibrate how quickly variola evolved and diversified. Each well-dated ancient genome adds a fixed point to the timeline, allowing researchers to refine estimates of when the major branches of the smallpox family tree emerged.
Questions of ethics
The study also comes amid growing attention to how ancient DNA research is conducted. Constanza de la Fuente Castro, of the Universidad de Chile, has raised concerns about the field. “The ancient DNA field has been in the spotlight due to two particular concerns,” she said, pointing to the issues of consent and the stewardship of human remains, and to what she describes as asymmetric research relationships between the Global South, where many samples originate, and the Global North, where much of the funding and authorship is concentrated.
She calls for journals and funders to require documented local co-leadership of studies, transparent records of where remains came from and what consent was obtained, and investment in laboratory capacity in the places where remains originate.
Such concerns are especially pointed for research on Indigenous remains. In many countries, Indigenous communities have historically had little say over how the bodies of their ancestors were collected, displayed and studied. Researchers and institutions have increasingly recognized the need to involve descendant communities in decisions about research, and some guidelines now treat community engagement as a basic requirement.
Unanswered questions
The genome comes from two individuals, so it cannot reveal how many different strains of smallpox reached the Americas or how the virus spread across the continent. The dates of the individuals span more than a century, leaving open exactly which epidemic they may have been part of.
Additional genomes from other regions and time periods could help reconstruct the routes by which the virus traveled, whether it arrived once or repeatedly, and how it changed as it moved through populations with no prior immunity.
The work shows how well-preserved remains can bear witness to one of the most consequential episodes in human history. The people of northern Chile who died in the decades after 1492 left behind not only their bodies but a molecular record of the virus that helped transform their world.
Notes
- González, B., et al. “The genomic identity of early smallpox in South America.” Science, 2026. DOI: 10.1126/science.aee6957.
- American Association for the Advancement of Science (AAAS). “Chilean mummies preserve ancient smallpox genome that traces disease to European colonization.” EurekAlert!, 30 July 2026. https://www.eurekalert.org/news-releases/1137580.