The origin story of syphilis goes back far longer than we thought

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About 13,700 years ago was roughly when humans first started populating South America and rapidly spread around the continent. And, based on this discovery, the bacteria of the Treponema pallidum lineage were already diverse and capable of infecting people by then. This Late Pleistocene divergence, the authors note in their study, hints at the ancient pan-human distribution. Various Treponema pallidum subspecies were probably our fellow travelers spreading globally with the first humans that migrated out of Africa.

But there’s much more we need to learn before the “Columbian” syphilis origin debate is settled.

Beyond the Columbian story

While the 1495 siege of Naples remains the moment syphilis etched itself into the European psyche as a new and terrifying plague, it was likely just one violent flare-up in a relationship between humans and Treponema pathogens that spans continents and millennia. What we don’t know is when and where the important turning points in this relationship took place.

It’s unclear when and why Treponema pallidum evolved its sexual transmission, so evidently present in the subspecies that caused the outbreak in Naples. It’s also unclear whether the 1495 pandemic was triggered by a newly imported strain or a mutation of a lineage already present in Europe. The team hopes analyzing other ancient pathogen genomes hosted by people from different places on the globe and different social contexts—hunter-gatherers, farmers, city dwellers—will answer at least some of these questions.

The problem is, it’s hard to infer a specific pathogen’s features from ancient genomes. “With the data we have today, we can’t say anything about the virulence of this ancient Treponema pallidum subspecies, about how the symptoms of the disease it caused looked like, or about its mode of transmission,” Bozzi says.

What we do know, however, is that thousands of years ago, the Treponema pallidum lineage was likely way more diverse than it is today. “In the future we’d love to look at broader ecological interactions between humans, animals, the environment, and the pathogens,” says Nelson. “We’d love to explore this diversity further.”

Science, 2026. DOI: 10.1126/science.adw3020



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