For centuries, the origins of leprosy in the Americas have been shrouded in mystery and misconceptions. Historically, the disease was believed to have been introduced exclusively by European colonizers following their arrival in the late 15th century. However, groundbreaking research now challenges this long-held assumption, revealing that a second species of bacteria responsible for leprosy, Mycobacterium lepromatosis, was infecting human populations in the Americas at least a millennium before European contact. This paradigm-shifting discovery, emerging from an extensive international collaboration led by the Institut Pasteur, CNRS, and the University of Colorado, urgently revises our understanding of the disease’s deep-rooted presence in Indigenous communities. Anticipated to be published in the prestigious journal Science on May 29, 2025, the study offers unprecedented insights into the pathogen’s ancient genomic footprints and its enduring persistence across an entire continent.
Leprosy, also known as Hansen’s disease, remains one of the most neglected bacterial infections globally, primarily caused by the species Mycobacterium leprae. Affecting an estimated 200,000 new individuals worldwide each year, the disease manifests as chronic skin lesions and nerve damage, often stigmatizing affected populations. While M. leprae has been extensively studied, much less is known about Mycobacterium lepromatosis, a related but distinct species that was identified relatively recently, first in clinical cases in the United States in 2008. Subsequent discoveries found M. lepromatosis circulating in red squirrels in the British Isles in 2016, hinting at a wider ecological and geographical presence than previously suspected. The new study spearheaded by the Laboratory of Microbial Paleogenomics at Institut Pasteur, in conjunction with over 40 researchers spanning multiple continents, meticulously analyzed DNA from nearly 800 samples encompassing both ancient human remains and modern clinical cases to reconstruct the evolutionary landscape of this elusive pathogen.
Utilizing state-of-the-art ancient DNA extraction and genome sequencing techniques, the researchers were able to recover genetic components of M. lepromatosis from archaeological specimens dated to approximately 1,000 years ago, hailing from regions in Canada and Argentina. Despite the vast geographical separation between these sites, genomic analyses revealed an astonishingly close relationship between the strains, indicating rapid and widespread dissemination of the bacterium throughout the Americas centuries before European arrival. Phylogenetic reconstructions demonstrated that although these strains represent two distinct branches within the Mycobacterium genus, they share a tighter genetic affinity with each other than with any other known pathogenic species, suggesting a unique and interconnected evolutionary trajectory specific to the American continent.
Further genomic characterization uncovered multiple previously unrecognized lineages of M. lepromatosis, including an ancestral branch that diverged over 9,000 years ago yet remains active in infecting humans today, particularly in North America. This finding not only pushes the timeline of the pathogen’s presence far deeper into prehistory but also unveils a long-standing diversification process that has thus far eluded scientific exploration. These revelations imply that the bacterial species responsible for leprosy in the Americas possesses a far more complex evolutionary and epidemiological history than previously conceived, possibly involving unknown animal reservoirs and environmental niches that have yet to be identified.
Intriguingly, the research also sheds light on the transcontinental movements of M. lepromatosis, notably connecting the strains found in British red squirrels to an American lineage introduced to the British Isles during the 19th century. This evidence underscores the ability of the pathogen to traverse vast distances alongside human or commercial activities, facilitating the introduction and establishment of leprosy bacilli across disparate regions. Such movements highlight the intricate relationship between human migration, commerce, and the spread of infectious diseases, emphasizing the importance of global surveillance and historical context in understanding present-day pathogen dynamics.
Dr. María Lopopolo, the study’s first author and a leading figure at the Laboratory of Microbial Paleogenomics, emphasized the transformative nature of these findings, stating that the recognized pre-European presence of M. lepromatosis redefines the epidemiological narrative surrounding leprosy in the Americas. The identification of the disease as endemic among Indigenous populations prior to European colonization challenges entrenched beliefs and calls for a reevaluation of historical medical interpretations. This evolving understanding fosters greater appreciation for the complex interplays between humans and pathogens over millennia and the ongoing legacy of ancient infections in contemporary communities.
A pivotal aspect of this research is its strong collaborative engagement with Indigenous communities whose ancestral remains were studied. Ethical considerations were paramount throughout the project; communities were integrally involved in decisions concerning the handling and analysis of archaeological specimens. The research team ensured that all ancient DNA and related materials were respectfully returned when requested, and employed adaptable data-sharing platforms that respected Indigenous data sovereignty and cultural sensitivities. This model of research exemplifies best practices for integrating scientific inquiry with social responsibility and community partnership, setting a precedent for future work in paleogenomics and infectious disease history.
Technically, the study combined high-throughput sequencing with advanced bioinformatics tools to meticulously assemble and compare ancient and modern genomes of M. lepromatosis. These approaches enabled the identification of genetic markers and evolutionary relationships that would have been undetectable through traditional microbiological methods. The integration of archaeological context, such as radiocarbon dating and anthropological data, enriched the interpretations and painted a comprehensive picture of the pathogen’s persistence and adaptation through diverse historical epochs and environments.
The revelations stemming from this research hold profound implications for contemporary public health and infectious disease management. Understanding the deep evolutionary roots and diversification of M. lepromatosis informs epidemiologists about the long-term dynamics of leprosy transmission, potential reservoirs, and reservoirs’ geographic distributions. It opens new avenues for investigating the potential existence of non-human hosts in the Americas and elsewhere, which could be critical in predicting and controlling future outbreaks. Moreover, the discovery accentuates the necessity of integrating ancient DNA studies into mainstream infectious disease research to uncover hidden dimensions of pathogen biology and history.
Lead author Nicolás Rascovan, helming the Laboratory of Microbial Paleogenomics at Institut Pasteur, highlighted the broader significance of the findings. By unraveling the ancient genomic signatures of M. lepromatosis, scientists can better appreciate the intricate evolutionary dance between humans and their microbial adversaries. Such insights pave the way for innovative strategies in tracking disease origins, understanding pathogen resilience, and ultimately, improving therapeutic interventions. The study exemplifies the power of combining ancient and modern genetic evidence to rewrite medical histories and deepen our grasp of pathogens that have shaped human societies across millennia.
The coming publication in Science marks a major milestone in microbial paleogenomics and infectious disease epidemiology. It demonstrates how meticulous cross-disciplinary investigations can dismantle historical narratives anchored in incomplete evidence and foster more nuanced, scientifically grounded understandings. This pioneering work not only addresses critical gaps in the history of leprosy but also serves as a beacon for future studies aiming to illuminate the ancient roots of other neglected tropical diseases, thereby enriching the tapestry of human-pathogen co-evolution.
In conclusion, the identification of Mycobacterium lepromatosis as an ancient, endemic leprosy pathogen in the Americas prior to European colonization revolutionizes our comprehension of the disease’s origins and dissemination. The study combines rigorous ancient DNA analysis, comprehensive evolutionary genetics, and ethical collaboration with Indigenous communities to highlight the complexity and persistence of a pathogen once overlooked. This research underscores the transformative potential of integrating paleogenomic methodologies into infectious disease studies and paves the way for nuanced future explorations of global disease histories.
Subject of Research: Human tissue samples
Article Title: Uncovering pre-European contact leprosy in the Americas and its enduring persistence
News Publication Date: 29-May-2025
Image Credits: © Nicolas Rascovan, Institut Pasteur
Keywords: Evolutionary genetics, Paleontology, Phylogenetics, Bacterial pathogens
