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Researchers from Trinity College Dublin have recovered and analysed the first ancient smallpox virus genomes ever identified in the Americas, providing the strongest direct evidence to date that the disease was introduced through European colonisation.
Smallpox, caused by variola virus, played a major role in the catastrophic population decline experienced by Indigenous peoples after European arrival. Such was the extent of those declines, that many claim smallpox and other introduced diseases entirely reshaped societies, killing hundreds of millions of people.
Until now, however, there had been no direct genetic evidence linking colonial-era outbreaks in the Americas to strains circulating in the Old World.
The study, just published in leading international journal Science, analysed ancient viral DNA recovered from two individuals from a local community buried in northern Chile between the late 15th and early 17th centuries. The researchers found that the viruses belonged to a now-extinct lineage of variola virus that sits evolutionarily between medieval European strains and the strains that circulated in later centuries.
Analysis of DNA from Chilean mummies has revealed the earliest known strain of ancient smallpox from the Americas. The findings offer the clearest genetic evidence yet that European colonization brought this disease to the New World. Smallpox was one of the deadliest diseases introduced to the Americas during European colonization. The rapid spread of the disease across North, Central, and South America is estimated to have resulted in the deaths of three to four million people, particularly among Indigenous populations with no prior immunity. However, due to the lack of ancient smallpox genomes from the Americas, much about the viral strains responsible remains in question. Bruno González and colleagues identified ancient smallpox virus DNA in two mummified Indigenous Inca-Early Colonial-era individuals recovered from northern Chile, who lived between 1492-1631 CE. The two ancient viral genomes were nearly identical, indicating the individuals were likely infected during the same outbreak or by the same circulating strain, providing rare direct molecular evidence of a smallpox strain circulating in colonial-era South America. According to González et al., the so-called “CAM9” smallpox lineage is the earliest known smallpox genome from the Americas.
By comparing the Chilean smallpox genomes with ancient and modern variola viruses, the authors found that the previously unknown and now-extinct lineage occupies an evolutionary position between early medieval European strains and the lineages that later gave rise to modern smallpox. This placement provides molecular evidence that smallpox reached the Americas through European colonization. The genomes also allowed researchers to track patterns of gene inactivation and mutation, revealing changing rates of viral evolution that appear linked to major demographic and epidemiological shifts during the colonial era.
For reporters interested in research integrity topics, study co-author Constanza de la Fuente Castro says, “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.”
Analysis of DNA from Chilean mummies has revealed the earliest known strain of ancient smallpox from the Americas. The findings offer the clearest genetic evidence yet that European colonization brought this disease to the New World. Smallpox was one of the deadliest diseases introduced to the Americas during European colonization. The rapid spread of the disease across North, Central, and South America is estimated to have resulted in the deaths of three to four million people, particularly among Indigenous populations with no prior immunity. However, due to the lack of ancient smallpox genomes from the Americas, much about the viral strains responsible remains in question. Bruno González and colleagues identified ancient smallpox virus DNA in two mummified Indigenous Inca-Early Colonial-era individuals recovered from northern Chile, who lived between 1492-1631 CE. The two ancient viral genomes were nearly identical, indicating the individuals were likely infected during the same outbreak or by the same circulating strain, providing rare direct molecular evidence of a smallpox strain circulating in colonial-era South America. According to González et al., the so-called “CAM9” smallpox lineage is the earliest known smallpox genome from the Americas.
By comparing the Chilean smallpox genomes with ancient and modern variola viruses, the authors found that the previously unknown and now-extinct lineage occupies an evolutionary position between early medieval European strains and the lineages that later gave rise to modern smallpox. This placement provides molecular evidence that smallpox reached the Americas through European colonization. The genomes also allowed researchers to track patterns of gene inactivation and mutation, revealing changing rates of viral evolution that appear linked to major demographic and epidemiological shifts during the colonial era.
For reporters interested in research integrity topics, study co-author Constanza de la Fuente Castro says, “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.”