Scientific research reveals insights into medieval leprosy

Medieval leprosy victim - photo courtesy University of BirminghamWhy was there a sudden drop in the incidence of leprosy at the end of the Middle Ages? To answer this question, biologists and archeologists reconstructed the genome of medieval strains of the pathogen responsible for the disease, which they exhumed from centuries old human graves.

The international team, which includes researchers from the University of Tübingen, Ecole Polytechnique Fédérale de Lausanne, and the University of Birmingham, have published their research in the journal Science.


Leprosy is caused by the bacterial pathogen Mycobacterium leprae. It was a common disease in medieval Europe, with as much as one in 30 people infected in certain areas. But at the turn of the 16th century, the disease abruptly receded over most of the continent (the disease is still very prevalent in other parts of the world – it can be found in 91 countries worldwide with about 200,000 new infections reported annually). The event was both sudden and inexplicable. Perhaps the pathogen that causes leprosy had evolved into a less harmful form? To find out, an international team of biologists and archaeologists joined forces.

They have reconstructed entire genome sequences of Mycobacterium leprae bacteria from five medieval skeletons that were excavated in Denmark, Sweden and the United Kingdom as well as seven biopsy samples from modern patients.


Reconstructing the bacterial genomes was no easy task, as the material available—from the human remains—contained less than 0.1% of bacterial DNA. The researchers developed an extremely sensitive method for separating the two kinds of DNA and for reconstituting the target genome with an unprecedented level of precision. “We were able to reconstruct the genome without using any contemporary strains as a basis,” explains study co-author and EPFL scientist Pushpendra Singh.

Scientific research reveals insights into medieval leprosyOne skeleton from Denmark showed extraordinary preservation of the pathogen DNA, allowing a genome reconstruction without using a modern reference sequence, which was never done before for an ancient organism’s genome. The scientists found that almost half of the DNA recovered from that particular specimen derived from Mycobacterium leprae bacteria; this is orders of magnitude higher than the amount of pathogen DNA usually observed in skeletons and modern patients. They furthermore found that the Mycobacterium leprae DNA was far better preserved compared to the human DNA, which may explain this unusually high amounts of bacterial DNA in these skeleton samples. According to the authors this may be due to the extremely thick and impervious waxy cell wall of the leprosy bacillus that protects their DNA from degradation. Therefore, the authors speculate that some bacterial DNA may be preserved much longer than any vertebrate DNA, which is usually less protected. “This opens the possibility that certain types of bacterial DNA may survive well beyond the maximum age for mammalian DNA of around one million years,” says Johannes Kraus of Tubingen University. He adds, “This gives us a real perspective to trace back the pre-historic origins of a disease.”

The results are indisputable: the genome of the medieval strains is almost exactly the same as that of contemporary strains, and its mode of action has not changed. “If the explanation of the drop in leprosy cases isn’t in the pathogen, then it must be in the host, that is, in us; so that’s where we need to look,” explains Stewart Cole, co-director of the study and the head of EFFL’s Global Health Institute.

Many clues indicate that humans developed resistance to the disease. All the conditions were ripe for an intense process of natural selection: a very high prevalence of leprosy and the social isolation of diseased individuals. “In certain conditions, victims could simply be pressured not to procreate,” Cole says. “In addition, other studies have identified genetic causes that made most Europeans more resistant than the rest of the world population, which also lends credence to this hypothesis.”


One interesting thing the researchers discovered was a medieval strain of Mycobacterium leprae in Sweden and the U.K. that is almost identical to the strain currently found in the Middle East. “We didn’t have the data to determine the direction in which the epidemic spread. The pathogen could have been carried to Palestine during the Crusades. But the process could have operated in the opposite direction, as well.”


In addition to the historical significance of the research, the study in Science is important in that it improves our understanding of epidemics, as well as how the leprosy pathogen operates. Sequencing methods designed as part of this research are among the most precise ever developed, and could enable us to track down many other pathogens that are lurking in foreign DNA. In addition, the incredible resistance of Mycobacterium leprae’s genetic material – probably due to its thick cell walls – opens up the possibility of going even further back in history to uncover the origins of this disease.

University of Birmingham has the only laboratories in the world that can pinpoint historical cases of leprosy by using highly specific fats as biomarkers. Professor David Minnikin, from the University of Birmingham’s School of Biosciences, added, “These comprehensive studies provide a sound framework for understanding the global history and current spread of leprosy. Knowledge of the location and origins of particular variants of the leprosy bacillus could be critical if problems develop with current anti-leprosy drug regimens.”


Click here to access the article Genome-Wide Comparison of Medieval and Modern Mycobacterium leprae from Science.

Click here to read more about Leprosy in the Middle Ages

Sources: University of BirminghamUniversity of Tübingen, Ecole Polytechnique Fédérale de Lausanne