The syphilis pathogen comes from America

The syphilis pathogen comes from America

Skeletal element from the upper hip that contained an ancient syphilis-like pathogen genome. © Dario Ramirez

During an epidemic in Europe in 1495, many people died of a disease that was new at the time: syphilis. The infectious disease did not originate in Europe, but in America, as new DNA analyzes of skeletal remains from the time before Columbus show. Extinct relatives of today’s syphilis pathogen were found there. The disease was introduced to Europe from the New World at the end of the 15th century and spread worldwide in the following decades due to European colonialism, the researchers report in “Nature”. This has clarified a long-debated question in the history of medicine.

Syphilis is a sexually transmitted infectious disease that is often fatal if left untreated. Survivors retain permanent physical and mental damage, such as changes to bones or teeth. The first documented and historically documented syphilis epidemic began in Europe in 1495. At the time the disease was still unknown. Because the plague occurred shortly after Columbus returned from America, experts long suspected that it could have been introduced through contact with people in the New World. The assumption was obvious because at that time many communicable diseases were actually introduced from Europe to America in the opposite direction.

But bone finds from the European Middle Ages have raised doubts about this theory in recent years. The skeletal remains date from before 1492 and show lesions typical of syphilis sufferers. This suggests that syphilis appeared in Europe before Columbus’ return and that the epidemic broke out in the late 15th century, independently of the colonization of the Americas. However, neither its origin in America nor in Europe has yet been clearly confirmed. “We cannot clearly identify the disease and its origin based on the lesions alone,” says co-author Casey Kirkpatrick from the Max Planck Institute (MPI) for Evolutionary Anthropology in Leipzig. Where and when the disease first broke out remains unclear.

Researcher doing laboratory work on pathological human bones
Darío Ramirez doing laboratory work on pathological human bones at the Max Planck Institute for Evolutionary Anthropology. © Rodrigo Nores

Syphilis and its relatives come from America

A team led by Rodrigo Barquera from the MPI for Evolutionary Anthropology has now clarified this question. The archaeologists and paleontologists examined bones and teeth with syphilis-like traces found in North and South America from the time before Columbus. The rare skeletal remains come from Mexico, Chile, Peru and Argentina, from around and before 1492. The researchers isolated the DNA of the pathogens from the remains and compared the genome with pathogens circulating today. The team reconstructed and identified five ancient genomes of pathogens. “Although the study presented some analytical challenges due to poor conservation status, we were able to confidently determine the relationships between these extinct forms and the strains that influence health worldwide today,” says Barquera’s colleague Lesley Sitter.

It turned out that the isolated bone DNA came from extinct relatives of today’s syphilis pathogen and other pathogens from the same disease family, yaws and bejel. All three diseases are caused by subspecies of the bacterium Treponema pallidum. “We found extinct sister lineages for all known forms of this disease family. Syphilis, yaws and bejel are modern remnants of pathogens that once circulated in America,” explains Barquera. The genomic data shows that these infectious diseases were actually circulating in America before Columbus arrived. “The data clearly show that syphilis and its known relatives originated in America,” says senior author Kirsten Bos from the MPI for Evolutionary Anthropology.

The DNA data from America also shows that cases of syphilis and yaws there exploded around the year 1500. Apparently the European conquerors also became infected with the syphilis pathogen. “Their introduction to Europe from the late 15th century onwards is consistent with these dates,” says Bos. The results also suggest that syphilis was introduced to Europe with Columbus’ return from the New World.

Global expansion of syphilis by colonialists

The global spread of epidemics in the following decades and centuries can therefore also only be attributed to the colonial period. The slave trade and the spread of Europeans to America and Africa may have facilitated this, according to the team. “While indigenous populations in the Americas suffered from the earliest forms of these diseases, Europeans played a critical role in their global spread,” says Bos. How the syphilis bacterium Treponema pallidum came to America remains unclear. It may have previously spread from an animal to humans in the Americas, or it may have been introduced by humans from Asia during the first settlement of the continent.

But if syphilis first appeared in America, why were bones with syphilis-like marks found in Europe older than 1492? The team suspects that these bone lesions come from other infectious diseases or other relatives of syphilis that have not yet been identified. “The search for these earlier forms continues, and ancient DNA will certainly be a valuable resource,” says senior author Johannes Krause from the MPI for Evolutionary Anthropology. “Who knows what older related diseases traveled around the world with humans and other animals before the syphilis family of pathogens emerged.”

Source: Rodrigo Barquera (Max Planck Institute for Evolutionary Anthropology) et al.; Nature, doi: 10.1038/s41586-024-08515-5

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