Ancient smallpox genome from Chilean mummies confirms colonial path
Viral fragments preserved in the Atacama Desert bridge medieval European lineages and modern variola, tracing the biological toll of transatlantic contact.

When Europeans crossed the Atlantic in the late fifteenth century, their ships transported invisible cargo that permanently altered human demography across two continents. Indigenous populations throughout the Americas had never lived alongside the variola virus, meaning their immune systems lacked any learned defense against it.12 As the pathogen moved into communities with no prior exposure, it encountered host populations where nearly every person was susceptible to infection. The resulting epidemics moved along established regional trade routes, transforming everyday social networks into transmission chains that killed millions of people and destabilized civilizations before colonial armies ever arrived.13
Historians have long chronicled this collapse through written colonial records and population estimates, yet the physical pathogen itself left almost no molecular trace from the earliest decades of contact. Chroniclers documented fevers, pustules, and sudden mortality, but early clinical descriptions cannot distinguish every rash illness or reveal how ancient strains relate to modern variants.3 For half a millennium, the biological record of the initial epidemics remained an inference supported by historical texts rather than physical genetic evidence.
Now, an analysis of ancient DNA recovered from two Indigenous individuals mummified naturally in the Atacama Desert of northern Chile has yielded the oldest known smallpox genome from the Americas.34 The work, led by Bruno Romero González and published in the journal Science, establishes a direct genetic link between the European disease and the devastation that followed transatlantic landfall.1 The reconstructed viral lineage, designated CAM9, represents a distinct evolutionary branch that fills a missing bridge between early medieval European strains and the modern lineages of variola virus that circulated before global eradication.35
How did smallpox spread through naive populations?
Smallpox depends entirely on human transmission, requiring direct contact with respiratory droplets or infectious bodily fluids shed by an infected person.3 Once inside a host, the variola virus multiplies silently during an incubation period, eventually causing high fever, intense aches, and a signature eruption of fluid-filled skin pustules. In an immunologically experienced population, surviving individuals carry antibodies that blunt later reinfection and slow the wider momentum of an outbreak. In an immunologically naive population, every human host provides fertile ground for viral replication, which accelerates transmission rates and pushes mortality far above normal levels.

Variola virus historically killed roughly 30 percent of people infected with its common form, leaving many survivors permanently scarred or blinded.3 In the Americas after 1492, the disease caused between three and four million direct deaths across Indigenous populations, according to published estimates.53 The rapid spread was facilitated by pre-existing trade pathways that linked coastal towns to inland administrative centers across the late Inca Empire.13 Because the virus could incubate quietly while an infected traveller was still walking between settlements, it consistently outpaced European reconnaissance expeditions.
What does the CAM9 genome reveal about viral evolution?
The CAM9 lineage represents an intermediate evolutionary bridge between medieval European lineages and modern variola strains.5 By analyzing molecular divergence across the poxvirus family tree, the researchers determined that this lineage split from a common ancestor around the year 1296, after diverging from early medieval European strains documented in Viking Age skeletons, but prior to the emergence of modern lineages.43 This placement confirms that CAM9 is a genuine early arrival in the Americas, rather than a subsequent reintroduction from a later historical wave.1
The genetic evidence came from two individuals buried at the Camarones 9 archaeological site, situated near the Pacific coast in northern Chile.1 One individual was a woman between 30 and 35 years old, and the other was a young man between 18 and 20 years old.1 In that hyper-arid desert environment, natural desiccation preserved human tissues and their microscopic passengers across centuries.13 When researchers processed bone samples, computational pathogen pipelines recovered variola virus DNA fragments from both individuals.1 The reconstructed viral genomes were nearly identical, demonstrating that both people had succumbed during the exact same local outbreak.51
Beyond confirming the pathogen's identity, the genetic sequences revealed changing tempos of evolutionary change across three distinct historical epochs. The paper reports a constant tempo of gene inactivation in the virus until the late sixteenth century, followed by a phase of evolutionary constraint during the height of colonial epidemics in the seventeenth and eighteenth centuries, when abundant susceptible hosts reduced selective pressures.41 Later, as human populations developed partial immunity and nineteenth-century vaccination campaigns began constraining transmission, the substitution rate experienced a measurable rebound, reflecting renewed adaptive pressure on the pathogen.42

What can two ancient genomes leave unanswered?
A sample of two individuals from a single coastal location cannot map the full continental path of smallpox. The radiocarbon dating of the two mummies spans a calibrated interval between 1492 and 1631, creating a temporal window of nearly 140 years that prevents researchers from matching these individuals to a specific recorded historical epidemic.13 Furthermore, two identical genomes from one archaeological site cannot determine whether smallpox was introduced to the Americas in a single initial event or through multiple independent introductions across different ports of arrival.13
Working with ancient pathogen genetic material also carries inherent technical limitations. Over hundreds of years, ancient DNA fragments break down into extremely short sequences and accumulate chemical damage, making recovery dependent on bioinformatic matching against modern reference genomes.12 While the phylogenetic analysis confidently positions CAM9 as an extinct sister lineage to modern variola, tracing its exact travel route south from primary colonial entry points remains speculative without comparable samples from intermediate geographical locations.1
Who directs the study of ancestral remains?
The molecular analysis of ancient human tissues has amplified ongoing ethical scrutiny over the stewardship and governance of Indigenous biological heritage. Because ancient DNA extraction requires the physical destruction of small bone or tooth fragments, sampling irreplaceable ancestral remains raises acute questions regarding consent and cultural preservation.5 For decades, scientific relationships between institutions in the Global North and archaeological materials sourced from the Global South have remained structurally asymmetric, concentrating funding, high-throughput sequencing technology, and lead authorships far from where the ancestral communities lived.53
Constanza de la Fuente Castro, a biological anthropologist at the Universidad de Chile and co-author of the study, argued that future research must shift from extraction toward equitable local partnership:52
The ancient DNA field has been in the spotlight due to two particular concerns. First, given the destructive nature of the analyses, unique and irreplaceable human remains are sampled worldwide, raising questions about consent, stewardship, and future preservation of these remains. Second, asymmetric research relationships persist: samples travel from the Global South while funding, analysis, and decision-making (and the first and corresponding authorships that follow) remain concentrated in Global North institutions. Community-engagement guidelines and critiques of "helicopter research" have pushed the field toward accountability, but adherence remains voluntary. I would like to see journals and funders require documented local co-leadership, transparent provenance and consent records, alongside sustained investment in laboratory capacity where the remains originate.5
Resolving these historical imbalances will determine how future biomolecular archaeology proceeds across South America. By establishing regional analytical facilities and involving descendant communities in scientific design, researchers can ensure that ancestral remains are investigated with local stewardship. The CAM9 genome demonstrates that ancient pathogen DNA can clarify the biological consequences of colonization, provided that scientific questions remain closely tied to the territories and communities where that history unfolded.
The record
32 sentences trace to 5 sources.
- 1 Two Chilean mummies hold the first genetic proof Europeans brought smallpox See the source
- 2 'Clear Evidence': Ancient DNA From Chilean Mummies Reveals Who Brought Smallpox to The Americas See the source
- 3 Chilean Mummies Yield the Earliest Known Smallpox Genome From the Americas See the source
- 4 The genomic identity of early smallpox in South America See the source
- 5 Chilean mummies preserve ancient smallpox genome that traces disease to European colonization See the source