For generations, the history of leprosy in the Americas has been framed as a consequence of the "Columbian Exchange," the vast transfer of plants, animals, culture, and human populations—along with their diseases—between the New World and the Old World following the voyages of Christopher Columbus. It was a long-held scientific and historical consensus that leprosy, a chronic infectious disease that has haunted human civilization for millennia, was introduced to the American continent by European colonizers and the subsequent transatlantic slave trade. However, groundbreaking research is now fundamentally altering this narrative, revealing that the history of the disease in the Western Hemisphere is far older and more complex than previously understood.
A major international study led by scientists from the Institut Pasteur, the CNRS, and the University of Colorado, in collaboration with a wide array of institutions across America and Europe, has uncovered evidence that a recently identified second species of bacteria responsible for leprosy, Mycobacterium lepromatosis, has been present in the Americas for at least 1,000 years. This timeline places the pathogen on the continent several centuries before the first European ships sighted American shores. The findings, which represent a significant shift in the fields of paleopathology and microbial evolution, are set to be published in the prestigious journal Science on May 29, 2025.
Leprosy, also known as Hansen’s disease, remains a significant public health challenge today. Classified by the World Health Organization as a neglected tropical disease, it continues to affect approximately 200,000 people every year through new diagnoses. While the primary cause of the disease has historically been attributed to the bacterium Mycobacterium leprae, the scientific community was introduced to a second causative agent, Mycobacterium lepromatosis, only relatively recently. This second species was first identified in 2008 in a Mexican patient living in the United States and was later found in 2016 to be infecting red squirrels in the British Isles. Despite its discovery, much about the origins, spread, and historical prevalence of M. lepromatosis remained a mystery until now.
To solve this evolutionary puzzle, the research team, spearheaded by the Laboratory of Microbial Paleogenomics at the Institut Pasteur—an entity also associated with the CNRS—and the University of Colorado, embarked on an exhaustive genomic survey. The study was a massive collaborative effort involving over 40 scientists from international institutions, including microbiologists, geneticists, and archaeologists. Crucially, the project was conducted in close partnership with Indigenous communities, ensuring that the study of ancestral remains was handled with the utmost ethical consideration and cultural sensitivity.
The researchers analyzed DNA from nearly 800 samples, a massive dataset that spanned both time and geography. These samples included ancient human remains recovered from archaeological excavations as well as modern clinical cases from patients presenting with symptoms of leprosy today. By comparing the genetic signatures of the ancient and modern bacteria, the team was able to reconstruct the evolutionary history of the pathogen with unprecedented precision. The results provided definitive proof that M. lepromatosis was not only present but was already widespread across both North and South America long before the arrival of Europeans.
Dr. Maria Lopopolo, the study’s first author and a researcher at the Laboratory of Microbial Paleogenomics at the Institut Pasteur, emphasized the magnitude of these findings. She noted that this discovery transforms the current understanding of the history of leprosy in America, showing that a form of the disease was already endemic among Indigenous populations well before the colonial era began. This realization challenges the traditional view of the Americas as a "pristine" environment regarding certain infectious diseases prior to 1492 and highlights the long-standing biological relationship between Indigenous peoples and the pathogens in their environment.
One of the most striking aspects of the study involved the use of advanced genetic techniques to reconstruct the full genomes of M. lepromatosis from ancient individuals discovered in locations as geographically diverse as Canada and Argentina. Despite being separated by several thousand kilometers, the ancient strains found in these regions, which date back approximately 1,000 years, were found to be remarkably similar in their genetic makeup.
In the complex evolutionary tree of the genus Mycobacterium, these ancient American strains belong to two distinct branches. However, the study found that these two branches are more closely related to each other than to any other known branch of the bacteria. The scientists concluded that such genetic proximity across such a vast geographic distance could only be explained by a rapid spread of the pathogen across the continent. It is likely that M. lepromatosis moved through human populations across the Americas within just a few centuries, a feat of transmission that suggests the pathogen was highly adapted to the movement and social structures of the continent’s early inhabitants.
Beyond the 1,000-year-old samples, the genomic analysis also identified several previously unknown lineages of the bacteria. Among these was an ancestral branch that appears to have diverged from the rest of the species’ known diversity more than 9,000 years ago. Remarkably, this ancient lineage has not vanished into history; the study found that it continues to infect humans in North America today. This discovery points to an incredibly deep and long-lasting diversification of the pathogen on the American continent. It also suggests that there is likely a vast, largely unexplored reservoir of genetic diversity within these mycobacteria that remains to be discovered by science.
The study’s findings also reached across the Atlantic, shedding new light on the 2016 discovery of M. lepromatosis in red squirrels in the United Kingdom. At the time, the presence of the American-associated pathogen in British wildlife was a source of scientific curiosity. The new analysis suggests a surprising reversal of the typical colonial narrative: rather than the disease moving from Europe to the Americas, the strains found in the UK squirrels appear to be part of an American lineage that was introduced to the British Isles during the 19th century.
This transatlantic jump likely occurred through human travel or commercial exchanges during a period of intense global trade. Once introduced to the British Isles, the pathogen found a new host in the local red squirrel population, where it has since persisted. This discovery serves as a powerful illustration of the pathogen’s modern ability to cross continents and adapt to new biological niches, driven by the interconnectedness of human activity.
Nicolás Rascovan, the lead author of the study and head of the Laboratory of Microbial Paleogenomics at the Institut Pasteur, noted that the scientific community is only beginning to understand the full scope of this pathogen’s global movements and diversity. He suggested that the study allows researchers to hypothesize the existence of as-yet-unknown animal reservoirs that may play a role in the persistence and spread of the disease. According to Rascovan, the study clearly demonstrates how the marriage of ancient and modern DNA analysis can rewrite the history of a human pathogen, providing vital context that helps scientists better understand the epidemiology of contemporary infectious diseases.
A defining characteristic of this research was its commitment to ethical collaboration with Indigenous communities. Recognizing the sensitive nature of working with ancestral remains, the research team involved Indigenous representatives in the decision-making process regarding the use of these remains and the interpretation of the resulting data. In a move toward restorative science, ancient DNA and any remaining materials were returned to the communities when requested. Furthermore, the data generated by the study was shared through ethical, adaptable platforms specifically designed to meet the expectations and requirements of Indigenous groups, ensuring that the descendants of those studied have agency over their genetic heritage.
As the scientific community prepares for the full publication of these results in Science, the implications of the study continue to resonate. By proving that leprosy has a pre-colonial history in the Americas, the research not only corrects the historical record but also provides a new framework for studying how pathogens evolve in isolation and how they react when suddenly thrust into a globalized world. The enduring presence of a 9,000-year-old lineage in modern North America serves as a sobering reminder of the persistence of such diseases and the importance of continued vigilance in global health efforts.
The study ultimately highlights the power of paleogenomics to act as a bridge between the past and the present. By looking back 1,000 years into the genomes of ancient microbes, scientists are gaining the tools necessary to address the infectious disease challenges of the 21st century. The history of leprosy in the Americas is no longer a simple story of colonial introduction, but a complex saga of ancient origins, rapid continental spread, and modern global migration.
