Spring 2008: Dynamic Forces

Kristen Harper with a human femur

the human story: Kristin Harper studies ancient human bones to develop the most comprehensive genetic analysis yet of the bacteria that causes syphilis.

Bryan Meltz

Tracing the Origins of Syphilis

A graduate student adds new knowledge to the debate

By Carol Clark

Did Columbus and his men introduce the syphilis pathogen into Renaissance Europe, after contracting it during their voyage to the New World? Or does syphilis have a much longer history in the Old World?

Graduate student Kristin Harper has taken the first phylogenetic approach to this centuries-old debate, heading up a groundbreaking study that provides new support for the Columbus theory of syphilis’s origin. The results of the most comprehensive comparative genetic analysis ever conducted on the Treponema pallidum family of bacteria related to syphilis were published in January in the Public Library of Science’s Journal of Neglected Tropical Diseases.

“We concluded that the closest relative of the modern syphilis strains of bacteria were strains collected in South America that cause the Treponemal disease yaws,” says Harper, a Howard Hughes Medical Institute predoctoral fellow in Emory’s Population Biology, Ecology, and Evolution program. “That supports the hypothesis that syphilis—or some progenitor—came from the New World.”

The preliminary results of the study won the Earnest A. Hooton Prize when Harper presented them at the 2006 American Association of Physical Anthropologists meeting.

“Syphilis was a major killer in Europe during the Renaissance,” says George Armelagos, chair of the Department of Anthropology and a member of the research team. Armelagos is a skeletal biologist whose research put him at the forefront of the syphilis debate thirty years ago. “Understanding its evolution is important not just for biology, but for understanding social and political history. It could be argued that syphilis is one of the important early examples of globalization and disease, and globalization remains an important factor in emerging diseases.”

Soft-spoken and petite, Harper sorts through piles of ancient human bones as she explains the telltale marks of Treponemal disease to visitors to the anthropology lab. “It’s sad to think of how painful this must have been,” she says, indicating a lesion in a thigh bone.

While it is generally agreed that the first recorded epidemic of syphilis occurred in Europe in 1495, controversy has raged ever since over the origin of the pathogen. Most of the evidence in recent years has come from bones of past civilizations in both New World and Old World sites, since chronic syphilis causes skeletal lesions.

In many cases, however, skeletal analysis is inconclusive, due to problems with pinpointing the age of the bones and the lack of supporting epidemiological evidence. Further complicating the research is the fact that Treponema bacteria cause different diseases that share some symptoms but have different means of transmission. Syphilis is sexually transmitted, but yaws and endemic syphilis are tropical diseases transmitted through skin-to-skin or oral contact.

One hypothesis is that a subspecies of Treponema from the warm, moist climate of the tropical New World mutated into the venereal subspecies to survive in the cooler European environment.

The phylogenetic analysis of twenty-six pathogenic Treponema strains indicated that yaws is an ancient infection in humans while venereal syphilis arose relatively recently. The study results are especially significant due to the large number of different strains analyzed, including two never-before-sequenced strains of yaws from Guyana—the only known active site of yaws infection in the Western hemisphere.

Harper is now studying a gene identified in the phylogenetic analysis that appears to be linked to the sexual transmission of syphilis. “We believe it could be used as a diagnostic tool,” she says. “For instance, when a child contracts a Treponemal disease, you could determine if the child may have been the victim of sexual abuse.”

She is simultaneously working on several other research papers, including one involving an outbreak of Treponemal disease among baboons in Tanzania, which could provide another important genetic clue to how the disease is transmitted in humans.

“By studying historical diseases, you can learn about trends in current ones,” says Harper, whose interest in the evolution of syphilis brought her to Emory to work with Armelagos. “I love research that tells a human story.”