Isolated Tribe Gives Clues to the Origins of Syphilis

Science, January 18, 2008

In 1494, King Charles VIII of France invaded Italy. Within months, his army collapsed and fled. It was routed not by the Italian army but by a microbe. A mysterious new disease spread through sex killed many of Charles’s soldiers and left survivors weak and disfigured. French soldiers spread the disease across much of Europe, and then it moved into Africa and Asia. Many called it the French disease. The French called it the Italian disease. Arabs called it the Christian disease. Today, it is called syphilis.

The sensational debut of syphilis inspired centuries of debate.

Some have argued that Columbus’s crew brought the disease from the New World to Europe; others say the disease existed unrecognized for centuries in the Old World before turning virulent. This week in the journal PLoS Neglected Tropical Diseases, a team of researchers argues that neither hypothesis is correct. Syphilis originated as a milder, nonsexual disease in the New World, they say, and it evolved into its current form after Europeans arrived. Among the evidence they offer is a mysterious disease restricted to an isolated tribe in a South American jungle. Its DNA, they argue, reveals that it is a kind of protosyphilis.

The disease was discovered in 1999 by a team of Canadian doctors who travel each summer into remote jungles in Guyana to provide medical care to the Akwio tribe. Michael Silverman, a clinician at the University of Toronto, noticed that some of the Akwio children had open sores on their arms and legs.

To Silverman, it seemed like a combination of two diseases, syphilis and yaws. The former, caused by bacteria known as Treponema pallidum pallidum, produces open sores. But it is spread through sexual contact and forms sores around the genitals. Another strain, T. p. pertenue, causes yaws, which is spread by skin contact rather than sex and produces sores on the limbs. But the Guyana disease was not quite like yaws either. That disease causes raspberrylike eruptions, not the open sores the doctors saw. “I thought, ‘This is bizarre,’” says Silverman.

The following year, Silverman and his colleagues proved that the disease was caused by a form of Treponema, which infected about 5% of the children in the tribe. They began treating them with penicillin. Just before boarding a flight for his 2005 mission, Silverman got a call from Kristin Harper, a graduate student at Emory University in Atlanta, Georgia. She was sequencing DNA from every known strain of Treponema and asked him to get her some from Guyana.

Harper thought genetic analysis could shed new light on the origins of syphilis. Until recently, the debate revolved around bones, which can be scarred by syphilis. Some researchers claimed to have found lesioned bones of Europeans who lived centuries before Columbus’s voyages; others dismissed those findings as inconclusive.

Harper and her colleagues hoped to reconstruct the evolution of different strains of Treponema by comparing their DNA. But gathering the DNA was difficult. Although syphilis is common, the other strains are rare, and none can be cultured easily outside its human host. To get the DNA samples, Silverman dipped swabs into sores, preserved them in alcohol, and sent them to Harper, who extracted fragments of Treponema DNA. Months later, Silverman got a call from Harper. “She said, ‘You found the origin of syphilis!’” he recalls.

When Harper and colleagues used the variations in the Treponema DNA to draw an evolutionary tree, the deepest branches belonged to samples of yaws from the Old World. Newer forms of yawslike diseases emerged from the ancestral bacteria. The strange Treponema strain in Guyana sat on a relatively young branch, suggesting that yaws had been carried into the New World by the first immigrants some 12,000 years ago, and that the Guyana strain evolved there. It shares a close ancestry with all strains of syphilis. The relationship also suggests that the Guyana strain is a transitional form that had already acquired some of syphilis’s traits, such as the open sores.

In this form, the bacteria could move easily through skin contact, because its hosts wore little clothing. But once the bacteria infected the more heavily clad European explorers, the researchers speculate, it may have had to find a new route of transmission. “You bring in the Europeans who only touch skin when they have sex, and it takes off as a venereal disease,” Silverman says. For reasons scientists don’t yet understand, the pathogen also evolved into a far more dangerous form that could trigger an epidemic in Europe.

John Logsdon, an evolutionary biologist at the University of Iowa in Iowa City, praises the research but doesn’t think it offers definitive proof of where syphilis came from. “There’s very little data to distinguish between the hypotheses,” he says. The new evolutionary tree is based on variations at only four sites in the Treponema DNA, which Harper agrees is a small number. One reason the data are so sparse is the challenging work conditions in the jungles of Guyana, where Silverman preserved samples in unrefrigerated alcohol—far from the ideal way to keep DNA from degrading.

Logsdon and Harper agree that the best way to test the new hypothesis would be to draw another evolutionary tree based on the entire genomes of the strains. But that may not be possible, as Silverman and his colleagues have not been able to get any more DNA from the Guyanese strain. On subsequent missions, they failed to find anyone infected with it. It appears that they have eradicated the disease. “We’re still looking for one more case,” says Silverman.