500-Year-Old Smallpox DNA Found

Oxford, September 16: Scientists have recovered fragments of ancient DNA from the variola virus, which causes smallpox, from the naturally mummified remains of two Indigenous people buried in northern Chile. The discovery is providing new clues about how the deadly disease reached the Americas and evolved over centuries.

The remains date from around 1492 to 1631, covering the transition from Inca rule to the Spanish colonial period. Researchers said the genetic material represents the first ancient smallpox genomes recovered from the Americas.

Smallpox was one of history’s most devastating infectious diseases. Its severe form, variola major, killed around 30% of infected people, although the fatality rate varied between outbreaks and populations. After centuries of outbreaks, a global vaccination and surveillance campaign led by the World Health Organization eventually eliminated the disease. The last known naturally acquired case was recorded in Somalia in 1977, and the WHO declared smallpox eradicated in 1980.

The Chilean discovery does not mean that the virus can return. Researchers found only damaged fragments of viral DNA preserved in the remains. They reconstructed the genetic sequences computationally and did not recover an intact virus or create a live pathogen.

An intact poxvirus requires a complete genome as well as proteins and enzymes needed to reproduce inside cells. The degraded DNA fragments found in Chile do not contain this complete biological machinery.

The ancient genomes nevertheless provide important information about smallpox’s history. Researchers found that the two Chilean viruses belonged to a now-extinct lineage that diverged from other known variola lineages around 1296. Their position on the evolutionary family tree, together with the dates of the remains, supports evidence that smallpox reached the Americas following European colonisation.

The study also sheds light on how variola became specialised to infect humans. During its evolution, some genes that were useful to poxviruses infecting multiple animal species became inactive or disappeared in variola. Scientists describe this process as reductive evolution.

The mummified individuals also had skin lesions. Earlier research had linked the marks to long-term exposure to naturally occurring arsenic in the region. The newly detected smallpox DNA confirms that both individuals had been infected with smallpox, but researchers said the genetic evidence cannot establish whether smallpox caused the particular skin lesions or their deaths.

The findings help fill a gap between previously known medieval European variola genomes and later strains, offering researchers a clearer picture of the virus’s evolution and spread through human populations.