Ancient DNA offers new evidence in long-standing syphilis theory

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The English, Germans and Italians called it the French disease. The Polish people called it the German disease, and the Russians blamed the Poles. In France, it was named the “Neapolitan disease” after the French army was infected during its invasion of Naples, Italy, in the first documented syphilis epidemic.

The origins of syphilis — a sexually transmitted infection that devastated Europe in the 15th century and is still seen today — remain murky, difficult to study and a matter of debate.

One long-held theory is that the disease originated in the Americas and migrated to Europe after Christopher Columbus’ expeditions returned from the New World, but a new study suggests that this is not the case. really more complicated.

Genetic information about ancient pathogens can be preserved, extracted and studied in bones, dental plaque, mummified bodies and historical medical specimens — a field known as paleopathology.

Research published Wednesday in the journal Nature used paleopathology techniques on 2,000-year-old bones found in Brazil in an attempt to shed more light on when and where syphilis originated. As a result of the study scientists recovered the earliest known genomic evidence of Treponema pallidum, the bacterium that causes syphilis and two other related diseases, reliably dated to well before the first trans-Atlantic contacts.

“This study is extremely exciting because it is the first truly ancient treponemal DNA recovered from archaeological human remains that are more than a few hundred years old,” said Brenda J. Baker, professor of anthropology at State University Arizona said. He was not involved in the study.

A complex disease caused by a complex bacterium

Untreated, syphilis can cause physical disability, blindness and mental impairment. As a sexually transmitted disease, it has long been stigmatized – so different populations have tried to blame outbreaks on neighboring groups or countries.

A skeleton found by researchers at Jabuticabeira II is shown.  - Jose Philippines

A skeleton found by researchers at Jabuticabeira II is shown. – Jose Philippines

Studying the disease and the pathogen responsible for it is very complex, said Molly Zuckerman, professor and co-chair of the New and Old World Bioarchaeology Laboratories at Mississippi State University, who was not involved in the research. .

“It was only in 2017 that researchers were able to culture T. p pallidum for the first time, even though we’ve known it to be the cause of syphilis for over a century,” Zuckerman said in an email. “It is expensive and very difficult to study in the laboratory. There are many reasons why, despite our best efforts, it is one of the least understood common bacterial infections.”

The timing and sudden onset of the first documented syphilis epidemic at the end of the 15th century has led many historians to conclude that it came to Europe after the voyage of Columbus. Others believe that T. pallidum bacteria have always had a global distribution but may have become rarer after it first appeared as a mild disease.

“It is very clear that Europeans brought several diseases (including smallpox) to the New World, decimating the native populations, so the hypothesis that ‘the New World brought syphilis to Europe’ was attractive to people certain,” said Sheila A. Lukehart, professor emeritus in the Department of medicine, infectious diseases and global health at the University of Washington, who was not involved in the study.

Syphilis is closely related but distinct from two other subspecies or lineages of treponemal disease, non-transmitted, non-sexually transmitted diseases with similar symptoms called bejel and yaws that were also the focus of the new research.

The team behind the new study examined 99 bones from the archaeological site known as Jabuticabeira II from the Laguna de Santa Catarina region on the Brazilian coast. Some bones had marks characteristic of infection with T. pallidum – the bacteria effectively eat away at the bones, leaving hollow lesions.

Bone samples from four people provided the team with enough genetic data to analyze, and one showed study author Verena Schünemann, assistant professor at the University of Zurich’s Institute of Evolutionary Medicine, what is described as a high-coverage genome, detailed enough to for fine- grain analysis.

The analysis showed that the pathogen responsible for the lesions was more closely related to the modern subspecies of T. pallidium that causes bejel, a disease found today in arid regions of Africa and the Middle East with symptoms similar to syphilis by him.

The result adds strength to previous suggestions that civilizations in the Americas had treponemal infections in pre-Columbian times, and that treponemal disease was already present in the New World at least 500 years before Columbus sailed.

Revealed from a bacterial family tree

Schünemann said that the new results do not mean that the venereal syphilis that caused the epidemic in the 15th century came to Europe from America at the time of Columbus. A similar study by her team previously found T. pallidum bacteria in human remains in Finland, Estonia and the Netherlands from the early modern period (early 1400s onwards), suggesting understanding that certain forms of treponemal disease, if not syphilis, were already in circulation. on the continent during Columbus’ voyage to the New World.

In addition, the genome obtained from the Brazilian sample provided a bacterial family tree dating back thousands of years, suggesting that T. pallidum bacteria first evolved to infect humans as far back as 12,000 a year ago. It is possible, said Schünemann, that the bacteria could be brought to America by the first inhabitants who crossed into the continent from Asia.

“I think the situation is much more complicated than the Columbian hypothesis could ever imagine,” she said.

Mathew Beale, a senior scientist in bacterial evolutionary genomics at the Wellcome Sanger Institute near Cambridge, England, agreed with Schünemann’s assessment, saying in an email that the study “did not prove or disprove the premise of the Columbia hypothesis itself – that Columbus voyage.” It led to the importation of Treponema and outbreaks in the 1500s and then to today’s syphilis.”

“This is mainly because the bacteria sequenced are not direct ancestors of the strain that causes modern syphilis. … (I)t is a common species. This may mean that the various treponematoses were already widely distributed throughout the world, and may even predate the ancient migration and population of the Americas,” said Beale, who was not involved in the research.

“Alternatively it could mean that many different treponematoses were present in the New World, and indeed Columbus and his colleagues imported one of these, which was only distantly related to the genomes ancient from this paper,” he said.

Further research into ancient genomes from around the world may solve the mystery, revealing which subspecies of bacteria were present in Europe and the New World before Columbus’ voyages, according to Lukehart.

“The biggest scientific question now is not about syphilis, but about the distribution of the three subspecies around the globe, especially in pre-Columbian samples,” Lukehart said.

“The modern tools available to extract DNA from ancient samples, to enrich the treponemal DNA, and to obtain deep sequencing from samples have rapidly increased our understanding of the Treponema.”

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