The recent discovery of ancient remains with signs of the disease shows how mysterious its origins are.

In June 1495, the Italian historian Niccolo Squillaci wrote a letter describing a horrific disease that was sweeping through Europe.

“There are itching sensations, and an unpleasant pain in the joints; there is a rapidly increasing fever,” he wrote. “The skin is inflamed with revolting scabs and is completely covered with swellings and tubercules, which are initially of a livid red color, and then become blacker.” And, tellingly, “It most often begins with the private parts.”

“I exhort you to provide some new remedy to remove this plague from the Italian people,” he concluded. “Nothing could be more serious than this curse, this barbarian poison.”

More than half a millennium later, there are some things we know about that “barbarian poison.” We know that it was syphilis, and that Squillaci’s letter was one of the first documents describing the first recorded epidemic of the disease. We know that it’s caused by a spiral-shaped bacterium called Treponema pallidum, and that it spreads through sexual contact. And we know that a cure wouldn’t be discovered until penicillin was found to be an effective treatment in 1943.

What we still don’t know, though, is where syphilis came from.

There are two main theories about the origins of the 1495 outbreak. The first, known as the Columbian hypothesis, holds that Christopher Columbus and his crew carried the disease from the New World back across the Atlantic. Records from the outbreak indicate that the disease hadn’t been seen before in Europe, Columbian proponents argue, meaning that timing-wise, a cross-continental import was the likeliest explanation.

    

“Most physicians felt that this was a new disease, that it hadn’t been seen before in Europe, and that view tended to prevail for quite some time,” said John Parascandola, a medical historian and the author of Sex, Science, and Sin: A History of Syphilis in America. “There were certain tempting reasons for people to accept that—blame it on the others, blame it on the outsiders. Before that, the French were blaming it on the Italians, the Italians were blaming it on the French, et cetera.” (As my colleague Naomi Sharp has noted, syphilis has consistently been attributed to foreigners across the globe; it’s also gone by “the Turkish disease,” “the Polish disease,” and “the Portuguese disease.)

But in the 20th century, a second theory emerged: the pre-Columbian hypothesis, which holds that the disease already had a long history in Europe, and that the epidemic seemed like a new disease only because it had previously been mistaken for something else. Proponents of the pre-Columbian hypothesis have argued that this could have been a particularly virulent strain that made it seem unfamiliar, or that medical information became more readily available with the invention of the printing press in the mid-15th century, making it less likely that syphilis would be confused with some other disease, like venereal leprosy.

Recently, a paper published online in the International Journal of Paleopathology, subtitled “Implications for the origins of syphilis,” claims to help clarify the issue. More than anything, though, it serves as a case study for just how murky the origins of syphilis remain, and how far scientists are from reaching a consensus.

The paper describes the case of an adult male skeleton found in the Chiu Chiu cemetery, a gravesite in northern Chile dating to roughly 210 B.C. The sternum and two of the vertebrae showed evidence of a thoracic aortic aneurysm, a heart condition that can be caused by late-stage syphilis.

“We reinforce a theory that’s been suggested for some time, that venereal syphilis was present in pre-Columbian times in the Americas,” said Mario Castro, a professor of morphology at the University of Desarollo in Santiago, Chile, and the paper’s lead author. “Our main objective was to describe this very clear-cut case of an aortic aneurysm,” but taken in conjunction with another case of a similar skeleton from the same time period, found in Saskatchewan, Canada, in the 1980s, “it makes sense to say we had syphilis at the time.”

But the connection is a tenuous one, said Molly Zuckerman, an assistant professor of biological anthropology at Mississippi State University. Syphilis is part of a category of diseases known as treponemal disease, a group that also includes yaws, a skin infection found in tropical parts of South America, Asia, and Africa; the Chiu Chiu skeleton, she says, could very well have been suffering from yaws instead.

“We’ve known that yaws and bejel [another treponemal disease] were all over the Americas before Columbus arrived,” she said. “They are ubiquitous in some skeletal samples, just all over the place.”

What’s more, the type of aneurysm the skeleton likely suffered, can also be caused by atherosclerosis. An atherosclerosis-induced aneurysm, Castro said, more often affects a different part of the artery, but Zuckerman argued that the distinction wasn’t enough to support a case for syphilis over yaws, atherosclerosis, or some other cause.

“Absence of evidence is not evidence of absence,” she said.

In 2008, a team from Emory University published a genetic analysis of treponemal bacteria. The bacterial strain that causes venereal syphilis, they found, is relatively new in human history, and most closely related to strains that caused yaws in South America. Based on their analysis, they offered a new theory for syphilis’s global spread.

“It is not clear whether venereal syphilis existed in the New World prior to Columbus’s arrival,” they wrote. “While it is possible that Columbus and his crew imported venereal syphilis from the New World to Europe, it is also possible that the explorers imported a non-venereal progenitor that rapidly evolved into the pathogen we know today only after it was introduced into the Old World.”

According to Zuckerman, the third theory is known as the “modified Columbian hypothesis,” so called because it tweaked the original hypothesis to account for new genetic evidence. Zuckerman and her colleagues made the case for this middle ground in a 2012 paper in Evolutionary Anthropology: “Columbus and his crew could have transported a New World, non-venereal treponemal infection to Europe upon their return,” they wrote, “which, once there, could have responded to dramatically different selection pressures with a new, sexual, transmission strategy.”

More recently, Zuckerman was also part of a team that published a 2011 paper in the Yearbook of Physical Anthropology reviewing 54 different reports of treponemal disease in pre-Columbian Europe. None of the cases, they argued, presented evidence strong enough—either in the dating of the bodies or the signs of syphilis they displayed— to validate the pre-Columbian hypothesis.

“Many of the reports use nonspecific indicators to diagnose treponemal disease do not provide adequate information about the methods used to date specimens, and do not include high-quality photographs of the lesions of interest,” the authors wrote. “Thus, despite an increasing number of published reports of pre-Columbian treponemal infection, it appears that solid evidence supporting an Old World origin for the disease remains absent.”

More broadly, though, the problem isn’t a lack of evidence; it’s an abundance of evidence on all sides. Just a few months ago, for example, researchers discovered 14th-century skeletons in Austria that they say show signs of congenital syphilis, which is transmitted from mother to child rather than sexually. Taken one way, this could refute the Columbian hypothesis, as the scientists who found the skeletons argue; taken another way, it could reinforce the modified theory.

The only thing the Austrian discovery seems to guarantee, in other words, is that these skeletons, like the one in Chiu Chiu and the one in Saskatchewan and so many others, will add another wrinkle to a debate that doesn’t seem likely to be resolved any time soon.

“I hate to say never, especially with increasing improvements in science, genetics, and the types of pathological studies done on bones, Parascandola said. “And someone could still find the perfect specimen” to definitively pinpoint the origins of syphilis. “On the other hand, I don’t feel confident that this will really happen at some point in the future.”