Science Notes – Studying the secrets of syphilis

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Skeletal remains from one of the individuals in the study, who was shown to have been infected with syphilis and was six months old at the time of death. The skeleton displays characteristic signs of a treponemal disease. (IMAGE: Rodrigo Barquera. Santa Isabel collection, Lab. of Osteology, ENAH, Mexico (permission no. 401.15.3-2017/1065 INAH))

While we have talked a lot about ancient DNA (aDNA) in ‘Science Notes’, it has mainly been in the context of decoding ancient human genomes. We have not really delved into the other applications of the methodology, including the detection of ancient pathogens. However, this is a quickly emerging area that could have a huge impact on how we are able to study health and disease in the past, and deserves some unpicking.

Before archaeologists had aDNA to guide them, most signs of disease or pathology were noted solely through the appearance of skeletal lesions. This is a relatively sound technique, but it does have some significant limitations, one of the most severe being that pathologies take a long time to affect the bone, so only those individuals who had lived for quite some time with their illness would display the marks of these conditions on their skeleton. Those who succumbed relatively quickly, by contrast, would be virtually indistinguishable from a ‘healthy’ person. Additionally, while some pathologies affect the skeleton in a very specific way, and hence are easily identifiable, there are many others that are much less specific in appearance and look similar to other diseases. Unsurprisingly, then, the ability to identify the presence of a pathology through its DNA is quite appealing for archaeologists.

Indeed, the aDNA of several different bacteria has already been successfully extracted from human bone and sequenced. The most notable instance was the identification of Yersinia pestis as the cause of the Black Death and the Justinian Plague, but others include the sequencing of the bacteria that cause tuberculosis and leprosy. One pathology that has so far eluded aDNA researchers, however, is syphilis, which is caused by the bacterium Treponema pallidum. Previously it had been thought that the bacterium was unable to be recovered from human remains. First, it has a thin cellular membrane and hence is easily destroyed by heat, detergents, and drying. Second, by the tertiary stage of the disease, which is usually the point at which diagnostic skeletal lesions appear, the number of bacteria in the body has significantly decreased.

This was unfortunate as syphilis and yaws – a predominately tropical infection that is part of the same family of treponemal diseases – cause similar bone lesion patterns. This means that the two cannot always be distinguished from each other visually, something that significantly hinders research into the evolution and spread of the disease. This uncertainty over diagnosis has meant that the key debate over whether syphilis was a New World disease that was brought to Europe during the colonial period or whether it was present in the Old World before such transatlantic interactions has never been thoroughly addressed.

Identifying the bacterium through aDNA would help to illuminate this matter – and it now seems that such a possibility could finally become a reality. A recent study has successfully recovered ancient DNA of the T. pallidum bacterium from archaeological remains. Researchers from the Max Planck Institute for the Science of Human History, the University of Tübingen, the National School of Anthropology and History in Mexico City, and the University of Zurich analysed five individuals excavated from the former Convent of Santa Isabel in downtown Mexico City, used by Franciscan nuns from 1681 to 1861. All displayed skeletal lesions that suggested they were affected by a treponemal disease and, using high-throughput sequencing techniques, the team was able to recover and sequence the whole genomes of Treponema pallidum from three of the individuals.

Even more interestingly, the study was able to distinguish between the subspecies Treponema pallidum pallidum, which causes syphilis, and Treponema pallidum pertenue, which causes yaws. They found that two of the individuals were infected with syphilis and the other with yaws. While this is still only a preliminary study and the technique’s limitations are still not fully known, these results open up the possibility of finally being able to identify cases of historical syphilis with confidence.

The paper outlining the study and its results can be accessed for free at https://doi.org/10.1371/journal.pntd.0006447.

This article appeared in CA 342.

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