For centuries, historical accounts have documented the catastrophic impact of smallpox on Indigenous populations across the Americas after European contact, but concrete genetic proof linking the virus’s arrival to colonization has remained elusive. Now, groundbreaking analysis of ancient DNA extracted from mummified remains recovered in northern Chile has delivered the most definitive scientific evidence to date confirming the deadly virus was introduced to the hemisphere from the Old World via colonial expansion.
Smallpox ranks among the most devastating infectious diseases in human history. Before its global eradication in 1980, achieved through decades of widespread vaccination campaigns, the virus killed roughly one in every three people it infected, and left most surviving victims with permanent, disfiguring scarring. Repeated outbreaks ravaged populations across Europe and Asia for centuries, before spreading to the Americas in the wake of Columbus’s 1492 voyage. Historical documents from colonial administrators, missionaries and early settlers already record that the virus killed millions of Indigenous people, who had no prior exposure or built-up immunity to the pathogen. But until now, this narrative has lacked solid molecular confirmation.
The new research, published Thursday in the journal *Science*, was led by a team of international geneticists and anthropologists. Led by Shigeki Nakagome, a geneticist at Trinity College Dublin, the team analyzed 13 ancient bone samples recovered from an archaeological site in Camarones, a region in northern Chile that has preserved numerous well-preserved pre- and post-contact mummified remains. The team’s sequencing uncovered clear fragments of smallpox viral DNA in the leg bones of two individuals: an adult man and an adult woman.
Radiocarbon dating and genetic analysis placed the deaths of these two individuals between 1492 and 1632, aligning perfectly with the earliest waves of European colonial expansion into South America. When researchers compared the viral genome recovered from the mummies to other known smallpox strains, it fell evolutionarily between medieval European smallpox variants and later New World strains. This phylogenetic placement confirms that the smallpox circulating in South America shortly after contact descended directly from European lineages.
Patricia Foster, a biologist at Indiana University who was not involved in the new study, noted that while the broad narrative of smallpox’s introduction via colonization has long been accepted, this research provides the hard genetic proof that settles decades of debate. “Nobody would ever question that smallpox came to this hemisphere from colonization, but this proves it,” Foster said.
While the study confirms the virus originated in the Old World, it leaves open key questions about exactly how it spread to the remote South American site where the mummies were found. The research team notes that it remains unclear which specific group of colonizers or traders first brought the virus across the Atlantic. It could have been carried by early European settlers exploring the South American coast, or spread indirectly via transatlantic slave trade routes that passed through Africa before reaching the Americas.
Notably, the Camarones site where the remains were found has no surviving historical records of early smallpox outbreaks, raising new questions about how the virus traveled so far south so quickly. The research team hypothesizes the virus may have spread along long-established Indigenous trade networks that connected communities across the Americas long before the first European settlers arrived, allowing it to reach remote inland and southern populations much faster than previously thought.
Beyond confirming the origin of the virus, the study also offers new insights into how smallpox evolved over time to become more deadly. Comparing the ancient strain to later variants shows the virus gradually silenced specific genes that allowed it to become more efficient at infecting and killing human hosts.
The research also puts a human face on the catastrophic demographic collapse that followed colonization. Both of the individuals found to carry smallpox were between 18 and 35 years old, and the disease was almost certainly the cause of their deaths. Constanza de la Fuente Castro, study coauthor and biological anthropologist at the University of Chile, emphasized the findings underscore how the devastation of smallpox reshaped the Americas, wiping out entire Indigenous communities and leaving surviving populations vulnerable to European conquest.
“This wasn’t just a cultural or demographic shift,” de la Fuente Castro said. “It’s literally written into biological evidence that we can still recover and read today.”