A long-standing historical narrative has held that leprosy, one of the world’s oldest and most stigmatized diseases, was introduced to the American continent by European colonizers during the age of exploration. This "Columbian Exchange" theory suggested that the arrival of settlers, and the subsequent transatlantic slave trade, brought various pathogens—including the bacteria responsible for leprosy—to populations that had no prior exposure. However, groundbreaking research from an international coalition of scientists is now overturning this consensus. According to a study to be published in the journal Science on May 29, 2025, a second species of leprosy-causing bacteria has been circulating in the Americas for at least a millennium, predating the arrival of Christopher Columbus and European settlers by several centuries.
The research, led by scientists from the Laboratory of Microbial Paleogenomics at the Institut Pasteur, in association with the CNRS and the University of Colorado, reveals that Mycobacterium lepromatosis has a much deeper and more complex history on the American continent than previously understood. This discovery not only shifts the timeline of the disease’s presence in the New World but also provides a significant new perspective on how human pathogens evolve, diversify, and migrate across vast distances. By analyzing nearly 800 samples ranging from ancient archaeological remains to modern clinical cases, the team has reconstructed a narrative of a pathogen that was already widespread across both North and South America long before the first European ships appeared on the horizon.
Leprosy, also known as Hansen’s disease, remains a significant public health challenge today. Classified as a neglected tropical disease, it continues to affect approximately 200,000 people annually, with new cases reported in various regions across the globe. For decades, the medical and scientific community primarily attributed the disease to the bacterium Mycobacterium leprae. It was only relatively recently, in 2008, that a second species, Mycobacterium lepromatosis, was identified in a Mexican patient in the United States. This second species was later found in 2016 to be infecting red squirrels in the British Isles, suggesting a wider ecological footprint than initially suspected. The new study published in Science focuses specifically on this second species, tracing its genetic lineage back through time to uncover its hidden history in the Western Hemisphere.
The investigation was a massive undertaking, involving over 40 scientists from international institutions, including microbiologists, geneticists, and archaeologists. Central to the study’s success was the collaboration with various Indigenous communities, ensuring that the research was conducted with respect for ancestral remains and cultural heritage. By examining the DNA extracted from human remains found in archaeological excavations—some dating back over 1,000 years—the researchers were able to piece together the genetic puzzle of M. lepromatosis. These ancient samples were compared against modern clinical data to create a comprehensive map of the pathogen’s evolution and movement.
"This discovery transforms our understanding of the history of leprosy in America," explained Dr. Maria Lopopolo, the study’s first author and a researcher at the Laboratory of Microbial Paleogenomics at the Institut Pasteur. According to Dr. Lopopolo, the data confirms that a form of the disease was already endemic among Indigenous populations well before the 15th century. This realization challenges the colonial-centric view of disease history and underscores the importance of utilizing advanced genomic tools to re-examine the past. The presence of the bacteria in individuals who lived a millennium ago suggests that the pathogen was a stable, if perhaps under-recognized, part of the microbial landscape of the pre-Columbian Americas.
One of the most striking findings of the study emerged from the comparison of ancient genomes reconstructed from remains found in Canada and Argentina. Despite the geographic distance of several thousand kilometers between these two regions, the ancient strains of M. lepromatosis were found to be remarkably genetically similar. Both samples dated to approximately 1,000 years ago, yet they appeared to belong to two distinct but closely related branches of the Mycobacterium evolutionary tree. These branches are more closely related to each other than to any other known lineage of the bacteria.
The scientists argue that such genetic proximity across such a vast distance implies a rapid spread of the pathogen across the continent. It is likely that the disease moved through human populations and perhaps animal reservoirs within just a few centuries, covering the span from the northern reaches of North America to the southern tips of South America. This rapid dissemination suggests that the Indigenous societies of the era were more interconnected than often portrayed, with trade, migration, and social contact facilitating the movement of the bacteria across diverse environments and climates.
Furthermore, the genomic analysis identified several previously unknown lineages of the pathogen. Most notably, the team discovered an ancestral branch of M. lepromatosis that diverged from the rest of the species’ known diversity more than 9,000 years ago. Remarkably, this ancient lineage is not an extinct relic; the study found that it continues to infect humans in North America today. This finding points to an incredibly ancient and long-lasting diversification of the pathogen on the continent. It also suggests that there is a wealth of unexplored genetic diversity within pathogenic Mycobacteria that remains to be discovered, potentially hidden in both historical samples and contemporary clinical cases.
The research also provides a surprising twist regarding the presence of M. lepromatosis in Europe. In 2016, the scientific community was surprised to find this specific species infecting red squirrels in the United Kingdom. At the time, the origins of this infection were unclear. However, the new analyses suggest that the strains found in British red squirrels are actually part of an American lineage. The data indicates that this lineage was likely introduced to the British Isles from the Americas during the 19th century, after which it spread within the local wildlife population.
This discovery highlights the ongoing and often bi-directional ability of pathogens to cross continents through human activity. While much of the historical focus has been on diseases moving from the Old World to the New World, this study illustrates a clear instance where a pathogen lineage from the Americas established itself in Europe during the modern era, likely through commercial exchanges or the movement of people and goods. It serves as a reminder that the global movement of infectious diseases is a continuous process that did not begin or end with the initial period of colonization.
"We are just beginning to uncover the diversity and global movements of this recently identified pathogen," said Nicolás Rascovan, the lead author of the study and head of the Laboratory of Microbial Paleogenomics at the Institut Pasteur. Rascovan emphasized that the findings allow scientists to hypothesize the existence of unknown animal reservoirs that may have played a role in the survival and spread of the bacteria over millennia. The study, he noted, is a prime example of how the integration of ancient and modern DNA can rewrite the history of human pathogens, offering a clearer picture of the epidemiology of contemporary infectious diseases.
Beyond the biological and historical revelations, the study is notable for its ethical framework. The research project was conducted in close and continuous collaboration with Indigenous communities, particularly regarding the use of ancestral remains. In many cases, ancient DNA research has historically been criticized for being extractive or insensitive to the descendants of the individuals being studied. To address this, the researchers involved Indigenous communities in the decision-making process concerning the use of remains and the interpretation of the resulting data.
Consistent with these ethical commitments, the ancient DNA and any remaining materials were returned to the communities when requested. Furthermore, the data generated by the study was shared via ethical and adaptable platforms designed to meet the specific expectations and data-sovereignty requirements of the Indigenous groups involved. This collaborative model ensures that scientific advancement does not come at the cost of cultural respect and that the history being uncovered is shared with those to whom it most directly belongs.
As the scientific community prepares for the full publication of these findings in Science, the implications for modern medicine and history are clear. The story of leprosy in the Americas is no longer a simple tale of colonial introduction. Instead, it is a narrative of a resilient pathogen that has been part of the human experience in the Western Hemisphere for thousands of years. By understanding the deep history of Mycobacterium lepromatosis, researchers are better equipped to monitor its current diversity and anticipate its future movements, ultimately contributing to the global effort to manage and eventually eliminate this ancient disease.
