Syphilis and Christopher Columbus have more in common than you might think. Both touched down on new continents and colonized local inhabitants at the end of the 15th century: Columbus the indigenous Americans, syphilis the Europeans. Both also sought a route to Asia.

Syphilis first erupted in Europe in 1494 in a French army camp, a year after Columbus returned from a voyage to America . The disfiguring disease spread between soldiers and their sexual partners, causing sores on their genitals, rectums or mouths. 

Within just five years, syphilis had spread through all of Europe. Soon after, it spread to India, China, and Japan. Sex, although not the only route of transmission, is an effective disease spreader.  

This so-called "Columbian hypothesis" argues that syphilis was brought over to Europe by sailors returning from their colonization of indigenous Americans. The idea is that new diseases were exchanged between Europeans and Americans as new goods were: Gunpowder for tomatoes; smallpox for syphilis.

A new study published December 18, 2024, in the journal Nature gives credence to this hypothesis. 

Kirsten Bos, an anthropologist at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, ran a genetic analysis of five skeletons found in South America. The analyses led Bos and her colleagues to believe a precursor to syphilis-causing bacteria had circulated in the Americas 8,000 years ago. 

"Four of the five skeletons [we analyzed] are dated before 1492, meaning that this pathogen diversity was already present in the Americas at the time of [Chrisopher] Columbian contact," said study author Bos.

Syphilis originated in America 8,000 years ago

To test the Columbian hypothesis, Bos and her colleagues performed a genetic analysis on bacteria in bone lesions in the five skeletons, which came from Chile, Argentina, Peru, and Mexico.

Their bacterial samples included three subspecies of the treponemal bacterial family, which are responsible for different treponemal diseases. One subspecies, T. pallidum, causes modern syphilis.

Bos compared the genetic differences of older treponemal subspecies with modern syphilis samples. That data allowed the team to extrapolate the time it took for the bacteria to evolve, and estimate when the pathogen emerged. 

Their analysis seemed to confirm that the syphilis-causing bacteria T. pallidum emerged from the 8,000-year-old precursor around the time of Columbus.

"Our model suggests syphilis first appeared on the scene around 500 or 600 years ago, either in the Americas, or in Europe (or elsewhere) from a [bacterial] strain introduced from the Americas," said Bos.

How did syphilis spread around the world?

The study provides compelling evidence that T. pallidum was widely circulating in the Americas before the arrival of Columbus from Renaissance Europe. Yet, it doesn't conclusively prove that syphilis was brought to Europe from the Americas. 

"[It shows that] that the Americas acted as a reservoir where [syphilis-causing bacteria] were widely circulating. It could still have come to Europe from elsewhere or have already been there," said Mathew Beale, a genomics expert at the Wellcome Sanger Institute in Cambridge, UK. Beale was not involved in the study.

Studies show that treponemal diseases may have been endemic in Northern Europe around the same time as Columbus's voyages or possibly even earlier.

The exact origins of syphilis are difficult to trace, said Kerttu Majander, an archeogeneticist at the University of Basel in Switzerland.

One hypothesis is that treponemal diseases have always been around, piggybacking onto humans as they migrated from Asia to the Americas, some 12,000 years ago.

"Another theory is that they're zoonotic, meaning [precursors of syphilis] jumped from animals to humans in America. But we haven't found evidence of animals with treponemal diseases yet," said Majander.

It's also unclear what caused modern syphilis to emerge as a highly transmissible sexually transmitted infection 500-600 years ago. 

"It could be that something caused treponemal bacterial species to recombine and cause more aggressive forms of syphilis, but we don't know," said Majander.

What makes it even more complicated is that syphilis and gonorrhea were often confused in historical records, and only formally recognized as separate diseases around 200 years ago.

"There is still historical debate about whether the ‘syphilis' outbreak described in the 15th Century was really caused by T. pallidum," Beale said.

Antibiotic-resistant strains of syphilis are a problem today 

Untreated, syphilis once disfigured people's bodies and caused paralysis, blindness, attacks of pain and even death.

The development of the antibiotic penicillin in 1943 eradicated the dangerous symptoms of syphilis, if not the disease itself.

But syphilis lives on. Sexual transmission causes over 8 million new cases each year, while congenital syphilis causes around 200,000 stillbirths. Cases are rising in young adults, too, and research suggests this could be linked to a rise in unprotected sex.

Antibiotic-resistant strains exist for T. pallidum, too, meaning deadlier syphilis infections are re-emerging. 

That's why studies like this are relevant, said Majander, especially if we want to eradicate syphilis: "[The study shows] that syphilis has the capability of adapting to any environment. It raises the question whether other treponemal diseases existed before, and whether new, more aggressive diseases could emerge in the future."

Edited by: Zulfikar Abbany

Sources:

Barquera, R., et al. Ancient genomes reveal a deep history of Treponema pallidum in the Americas. Nature (2024). https://doi.org/10.1038/s41586-024-08515-5

Majander, K., et al. Redefining the treponemal history through pre-Columbian genomes from Brazil. Nature 627, 182–188 (2024). https://doi.org/10.1038/s41586-023-06965-x