The clinical trial evaluated the safety and efficacy of an innovative CAR-T cell immunotherapy that is specifically designed to attack cancerous T cells. Participants in the trial had been diagnosed with rare cancers — T cell acute lymphoblastic leukemia or T cell lymphoblastic lymphoma — and had run out of treatment options after standard therapy proved ineffective for them. With the new immunotherapy, most of the patients in the study who received the full dose of cells achieved full remission of their cancer.

The trial’s results were published May 30 in the journal Blood.

“For patients with these rare and aggressive cancers, who have no other options, this has the potential to become a transformative advance in the field,” said senior author John F. DiPersio, MD, PhD, the Virginia E. & Sam J. Golman Professor of Medicine at WashU Medicine, who first developed the therapy in his lab at WashU Medicine. “The trial demonstrated a high likelihood of response to the therapy and even remission. This CAR-T cell treatment shows promise in becoming a ‘bridge-to-transplant’ therapy for patients who would otherwise not be eligible for stem cell transplantation, which is the only potentially curative treatment for these blood cancers.”

Larger studies with more patients and longer follow-up are necessary before the researchers can determine whether this new therapy could be curative on its own.

The current trial included 28 adult and adolescent patients with T cell acute lymphoblastic leukemia and T cell lymphoblastic lymphoma that either returned after several lines of therapy or that never responded to treatment. About 1,000 people are diagnosed with these cancers annually in the U.S. If the cancer does not respond to treatment or returns after initial treatment, patients survive only six months, on average, and less than 7% are still living at the five-year mark.

The therapy, called WU-CART-007, was developed by Wugen, a WashU biotech startup company founded by DiPersio and other WashU Medicine investigators, including Matthew Cooper, PhD, who co-founded the company when he was on the WashU Medicine faculty and now serves as Wugen’s chief scientific officer. The researchers worked with WashU’s Office of Technology Management (OTM) to launch the company in 2018. The clinical trial was conducted in Australia, Europe and multiple sites across the U.S. For the St. Louis site, the trial was conducted at Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine.

The trial design included a dose-escalation phase, which determined the recommended dose of therapeutic cells that patients would receive for the second phase of the trial. Dose escalation helps determine the largest dose of CAR-T cells that patients can receive and still have manageable side effects. Thirteen patients received the full dose of 900 million CAR-T cells after undergoing a procedure to clear the patients’ own immune cells. This procedure — called lymphodepletion — reduces immune cells, making room for the new therapeutic T cells to establish themselves and expand in number. Two of these patients died from their cancer or treatment complications, such as infection, during the study period.

Of 11 patients who could be evaluated after treatment, the overall response rate was 91%, meaning 10 patients either showed no signs of cancer after treatment or their cancer cell burden was reduced significantly. Eight out of 11 patients (72.7%) achieved complete remission. At the study’s data cut off, six who underwent a transplant remain in remission, with no evidence of disease, six to 12 months later.

“These response and remission rates — ranging from 70%-90% of patients — are much higher than we would expect from standard-of-care for this cancer type, which typically leads to remission in only 20%-40% of patients,” said first and corresponding author Armin Ghobadi, MD, a professor of medicine and clinical director of the Center for Gene and Cellular Immunotherapy at WashU Medicine. “These responses are remarkable because the patients in this trial had run out of options. They had very aggressive cancers return after several lines of therapy, including several who relapsed after an earlier stem cell transplant.”

Most patients (88.5%) experienced cytokine release syndrome as a side effect of the immunotherapy, and these cases were predominantly mild or moderate. Cytokine release syndrome is a common side effect of CAR-T cell therapy that occurs when large numbers of immune cells release chemicals that cause a full-body inflammatory response. About 19% of the patients experienced more-severe cytokine release syndrome. A small number of patients experienced rarer side effects, such as neurotoxicity syndrome and low-grade graft-versus-host disease. Adverse events were managed with additional therapies.

Off-the-shelf cell therapy

The immunotherapy evaluated in the trial is considered a “universal” CAR-T cell therapy because — harnessing CRISPR gene editing technology — it can be produced from cells donated by any healthy individual and used to treat any patient with a T cell cancer. In contrast, approved CAR-T cell therapies are adapted from the patient’s immune cells. The cells must be collected from the patient and shipped to a manufacturing facility to be made and then shipped back, a process that typically takes three to six weeks. In contrast, universal CAR-T cell therapies can be made ahead of time, stored frozen and be readily available “off-the-shelf,” greatly reducing the wait time before therapy can begin.

Using CRISPR gene editing tools, the production process deletes the T cell receptor from the donor cells, greatly reducing the risk of graft-versus-host disease, in which donor T cells attack healthy tissue. Removing another key antigen also prevents the CAR-T cells from attacking one another. The types of rare cancers in this study presented a unique challenge: the therapeutic cells and the cancer cells are both T cells, so steps must be taken to prevent the therapeutic T cells from mistaking one another for the cancer and causing CAR-T cell fratricide. All other approved CAR-T cell therapies target B cell cancers, which do not have this T cell self-targeting complication. After using CRISPR gene editing to modify the CAR-T cells to prevent these harmful side effects, the cells are further engineered to target a protein called CD7 on the surface of cancerous T cells to then destroy the cancer.

“A larger international clinical trial of this therapy is already underway,” DiPersio said. “We must complete this larger trial first, but we are hopeful this universal CAR-T cell therapy can become an approved treatment for patients with deadly T cell cancers.”

This question is at the center of new research co-led by Texas A&M University Department of Oceanography Associate Professor Jinbo Wang, whose work is featured on the cover of the April 17 issue of Nature. It’s a big moment for Wang and his colleagues and the global science community — marking a milestone in a billion-dollar, international water mission two decades in the making, and reflecting Texas A&M University’s long-term strategy to grow its leadership in satellite oceanography and climate research.

Wang joined Texas A&M after working at NASA’s Jet Propulsion Laboratory (JPL) in California for over nine years, where he helped lay the groundwork leading to this research alongside colleagues at JPL and France’s space agency, CNES (Centre National d’Études Spatiales) and Caltech. The recent Nature paper builds on foundational work developed by these teams during the last two decades.

What’s An Eddy — And Why Should We Care?

An eddy is like a mini whirlpool in the ocean. Picture swirling water behind a rock in a river — eddies in the ocean work in a comparable way, only much bigger and more difficult to observe. Some stretch for hundreds of kilometers and help move heat, nutrients and energy across the globe. They are vital for climate, weather and marine life.

While scientists have long studied currents of large eddies, the smaller ones — called submesoscale eddies — are notoriously difficult to detect. These currents, which range from several kilometers to 100 kilometers wide, have been the “missing pieces” of the ocean’s puzzle — until now.

New Eyes On The Ocean

Using data from the new Surface Water and Ocean Topography (SWOT) satellite, Wang and his collaborators at JPL, CNES and Caltech finally got a clear view of these hard-to-see currents.

“For the first time, we can directly observe small-scale ocean processes across the globe,” Wang said. “And it turns out they are a lot stronger than we thought.”

This breakthrough comes from the SWOT satellite, which uses a Ka-band radar interferometer to measure subtle changes in sea surface height with millimeter precision. The instrument has revealed swirling patterns and internal ocean waves — features that, until now, had never been captured at this scale from space.

“These smaller currents carry surprisingly large amounts of energy,” Wang explained. “They play a huge role in moving heat between the upper and deeper parts of the ocean and shaping how the ocean sustains its ecosystem and interacts with the atmosphere. That means they can influence marine food webs and weather patterns, like how hurricanes form and where they go, or how events like El Niño and La Niña develop. These are not just ocean features — they connect directly to the climate systems that impact all of us.”

A Happy Surprise — And A Global Breakthrough

This level of success wasn’t guaranteed. While SWOT met its science requirements, many scientists — including Wang — were not sure it would be sensitive enough to measure these subtle sea surface changes. But the engineering team behind the satellite beat expectations.

“I was pessimistic about the expected outcome before the satellite launch,” Wang said. “But the satellite performed four times better than expected. That surprise is what made this breakthrough possible.”

With better-than-expected data, the team showed that submesoscale motions — especially the spiral-shaped eddies and long internal solitary waves — are far more powerful and frequent than previously believed. These small but mighty movements stir up the ocean, helping mix warm and cold water, transport energy over long distance, which affects ocean circulation, eventually weather and climate. The study highlights the potential of these new data in helping scientists to improve their numerical models for climate predictions.

Global Teamwork, Decades In The Making

This research was made possible by the SWOT mission, a $1 billion joint effort between NASA and CNES with contributions from the U.K. and Canadian space agencies. The mission development has involved a large international team and more than 20 years of planning, testing and innovation.

“We’re building on work that started two decades ago,” said Dr. Shari Yvon-Lewis, head of the Texas A&M Oceanography Department. “Many people who helped design this satellite and the science have since retired. It’s a tribute to long-term vision, teamwork and dedication.”

Hiring Wang was a key part of Texas A&M’s investment in expanding its expertise in satellite oceanography — an area critical for understanding ocean physics and its role in the climate system. His experience at JPL and leadership in global collaborations like SWOT have positioned the university at the forefront of space-based ocean research.

Wang is also leading a NASA Ocean AI working group focused on how artificial intelligence and machine learning can help analyze existing and future satellite data and help future mission design. He is keen to contribute to the next big satellite mission.

For now, having his work featured on the cover of Nature is a moment to celebrate — and a reminder of how much the ocean can teach us.

“This is just the beginning,” Wang said. “We finally have the tools to see what’s been hiding in plain sight.”

This creature, called Westlothiana lizziae, is one of the earliest examples of a four-legged animal that had evolved from living underwater to dwelling on earth. It, and other stem tetrapods like it, are common ancestors of the amphibians, birds, reptiles and mammals that exist today, including humans.

Despite its significance, researchers had never determined an accurate age of the fossil. But thanks to new research out of The University of Texas at Austin, scientists now know that the Westlothiana lizziae, along with similar salamander-like creatures from the same spot in Scotland, are potentially 14 million years older than previously thought.

The new age — dating back to 346 million years ago — adds to the significance of the find because it places the specimens in a mysterious hole in the fossil record called Romer’s Gap.

The research, published recently in the journal PLOS One, was led by Hector Garza, who just graduated with his doctoral degree from the Department of Earth and Planetary Sciences at the UT Jackson School of Geosciences. Garza took a risk when he embarked on his mission to date the ancient fossils using a geochemical technique called radiometric dating.

That’s because while geoscientists can use zircon crystals to determine how long ago a rock was formed, not all rock types are amenable to this type of analysis. And the site in Scotland where the fossils were discovered was near ancient volcanoes whose lava flows had long hardened into basalt rock, where zircons do not typically form. Fellow scientists warned Garza that chemically dating the rocks might be fruitless.

“I think that was one of the reasons why no one tried to go into them before,” Garza said. “Because of all the time and effort that it takes to obtain the zircons and then taking the risk of not finding any.”

But he got lucky. As mud cascaded down from the volcanoes, the flowing lava and debris eroded sediment that contained zircons, which got swept into a lake where limestone was forming, entombing these early tetrapod creatures.

Garza X-rayed 11 of the rock samples at the Jackson School and was able to extract zircons from the rock surrounding six of the fossils. He then conducted uranium-lead laser dating on the zircons at the University of Houston to determine their oldest possible age.

Before Garza’s gamble, scientists had figured the fossils were as old as similar fossils from around the world — about 331 million years old.

The more accurate, older maximum age of 346 million years is significant because it places the specimens in Romer’s Gap. This is a time period from 360 to 345 million years ago where, for reasons scientists are not exactly sure of, very few fossils have been discovered. It is during this crucial point in history that water-dwelling fish took an evolutionary leap, growing lungs and four legs to become land animals. This is one of the most pivotal milestones in the history of animal evolution.

“I can’t overstate the importance of the iconic East Kirkland tetrapods,” said Julia Clarke, professor at the Jackson School and co-author of this paper. “Better constraining the age of these fossils is key to understanding the timing of the emergence of vertebrates on to land. Timing in turn is key to assessing why this transition occurs when it does and what factors in the environment may be linked to this event.”

The site in Scotland where the fossils were found is the East Kirkton Quarry, a veritable treasure trove of early tetrapod records. Seven stem tetrapod fossils, including the Westlothiana lizziae, have been found there. Hundreds of millions of years ago when these early four-legged creatures roamed, this site was a tropical forest with nearby active volcanoes, a toxic lake, and a diverse plant and animal community.

The National Museum of Scotland provided Garza with bits of rock that surrounded the fossils to use for the sampling. Other study co-authors are Associate Professor Elizabeth Catlos and Michael Brookfield, both of the Department of Earth and Planetary Sciences at the Jackson School, and Thomas Lapen, professor and chair of the Department of Earth and Atmospheric Sciences at the University of Houston.

Quantum electrodynamics – competition for precision

Quantum electrodynamics (QED) is the fundamental theory describing all electromagnetic phenomena including light (photons). At the same time, it is the most precisely tested theory in physics at all. It has been stringently tested in various ways up to 0.1 parts per billion. But it is just the very strength of this theory that drives physicists to test it even more rigorously and to explore its possible limits. Any significant deviation would be a hint for new physics.

QED understands the electromagnetic interaction among charged particles as the exchange of “virtual” photons – the way electrons in an atom “talk” to each other and to the nucleus – and with themselves via emission and reabsorption of a photon, a QED effect called “self energy.” Furthermore, it turned out that the physical vacuum is not empty but filled with virtual particles such as electron-positron pairs which appear all the time “out of nothing” but have to disappear within the limits set by the uncertainty principle of quantum physics. Though this might sound spooky, it is just the way to explain the underlying physics of experiments performed in atomic physics already in the 1940s.

A state-of-the-art access to QED phenomena is the so-called g-factor of the electron which describes the relation of its mechanic (intrinsic angular momentum: spin) and magnetic properties. According to Dirac’s theory (relativistic quantum mechanics), the g-factor of the free electron should be exactly 2. However, various QED interactions change the g-factor and lead to a small but precisely measurable deviation from the value 2. QED effects depend in a strong nonlinear way on external fields. Electrons experience the extremely high electric field due to the high nuclear charge in heavy elements. The simplest systems are hydrogen-like highly charged ions which have been investigated both theoretically and experimentally with great success [1].

In a joint collaborative experimental-theoretical work, researchers at the Max Planck Institute for Nuclear Physics in Heidelberg have now investigated the g-factor of the outermost bound electron in lithium-like tin. This system is similar to hydrogen but adds the interaction with the two tightly-bound electrons of the inner atomic shell.

Theory: ab initio QED calculations

An ab initio calculation takes into account all electromagnetic interactions among the constituents – here of a Lithium-like ion – on a fundamental level including QED effects up to a certain degree. Electron structure effects where the electrons exchange photons are incorporated into the calculations, as well as QED screening effects, where the electron interacts both with the other electrons and with itself or with the vacuum. The ab initio prediction has been further improved by using the two-loop QED contribution extracted from the recent measurement in hydrogen-like tin [33] scaled to the lithium-like electron case. This yields an “experimentally enhanced” theoretical prediction of

g_th = 1.980 354 797(12)

with the uncertainty given in parentheses. Compared to the hydrogen-like case, this is overall a 25-fold improvement.

Experiment: counting spin flips

The measurement of the g factor of the bound electron was performed using the cryogenic Penning trap ALPHATRAP at MPIK. The strong magnetic field inside the trap leads to a characteristic motion of the ion confined by the field as well as to a precession of the spin of the outer electron like a tiny magnetic spinning top. The g factor can be extracted from the ratio of the ion’s motional frequency and the precession frequency while the magnetic field is eliminated from this calculation. The ion motion can be detected directly from small induced electric signals in the trap electrodes of the “precision trap.” To determine the precession frequency, microwave radiation is sent into the trap which can induce a spin flip, a change of the orientation of the spin (due to quantisation there are only two measurable spin states “up” and “down”). The rate of spin flips reaches a maximum when the microwave matches resonantly the precession frequency.

Results and outlook

The experimental value for the g factor of the lithium-like tin ion is

g_exp = 1.980 354 799 750(84)_stat(54)_sys(944)_ext

with the statistical, systematic and external uncertainties given in parentheses. The external uncertainties are dominated by the ion mass uncertainty, currently limiting the experimental accuracy. The overall accuracy is 0.5 parts per billion. The experimental result agrees well with the theoretical prediction given above within the uncertainty of the calculation. On the experimental side it is feasible to improve the precision of the mass value by more than an order of magnitude and consequently enhance the precision of the g factor if motivated by advancements in theory. In the future, measurements of heavier lithium-like systems such as ²⁰⁸Pb⁷⁹⁺ and the expected progress in two-loop QED calculations will provide even better tests in the strong electric field regime using highly charged ions. The advanced theoretical methods developed here for interelectronic QED effects can be applied to g-factor calculations of more complex ions (boron- or carbon-like), parity non-conserving transitions in neutral atoms and other effects.

In the new study, an international team of 21 scientists from ten countries used eight glacier models to calculate the potential ice loss from more than 200,000 glaciers outside of Greenland and Antarctica. The team evaluated a wide range of global temperature scenarios, assuming that temperatures would remain constant for thousands of years in each scenario.

“The choices we make today will resonate for centuries, determining how much of our glaciers can be preserved,” says Harry Zekollari, co-lead author from Vrije Universiteit Brussel, who began this research as a postdoctoral fellow at the Chair of Glaciology in the Department of Civil, Environmental and Geomatic Engineering (D-BAUG) at ETH Zurich.

Looking beyond 2100 reveals new insights

In all scenarios, the glaciers lose mass rapidly over decades and then continue to melt at a slower pace for centuries — even without additional warming. This long-term response means glaciers will continue to feel the effects of today’s heat far into the future, gradually retreating to higher altitudes before reaching a new equilibrium.

“One of the key strengths of our study is that we were able, for the first time, to project global glacier evolution over multi-centennial timescales, and did so using eight models instead of one or two,” explains Harry Zekollari. “Most glacier studies stop at 2100, which is problematic when simulating the long-term impact of today’s climate policies, given the long-term response of glaciers over time.”

For example, while studies limited to the year 2100 estimate that around 20 per cent of today’s glacier mass will be lost regardless of future warming, the new study reveals that nearly twice as much would vanish under present-day conditions when multi-centennial timescales are considered. “We find that around 40 per cent of glacier mass is effectively ‘doomed’ to disappear,” says co-lead author Harry Zekollari.

Melting glaciers reveal the reality of global warming

“Glaciers are good indicators of climate change because their retreat allows us to see with our own eyes how climate is changing. However, since they adjust over longer timescales, their current size vastly understates the magnitude of climate change that has already happened. The situation for glaciers is actually far worse than visible in the mountains today,” says co-lead author Lilian Schuster from the University of Innsbruck.

Beyond contributing to sea-level rise, glacier loss has far-reaching consequences. It threatens freshwater availability, increases the risk of glacier-related hazards such as floods and landslides, and jeopardizes glacier-fed tourism economies. These cascading impacts will be felt across regions and generations.

“These effects underscore the critical importance of present-day climate policies,” says Harry Zekollari. “Our study makes it painfully clear that every fraction of a degree matters. If we manage to limit global warming to +1.5°C instead of +2.7°C, we could still save twice as much glacier ice.”

Current policies are projected to lead to an average global warming of around +2.7°C. As Zekollari emphasizes, the degree of warming between +1.5°C and +3.0°C plays a decisive role in glacier loss. Put simply: for every additional 0.1°C of warming, the world risks losing approximately 2per cent more of its glacier ice.

Contributing to the UN-Year of Glaciers’ Preservation

“This study is a major contribution to the United Nations International Year of Glaciers’ Preservation, emphasizing the urgent need for global climate action to protect the world’s glaciers,” says Daniel Farinotti, Professor of Glaciology at ETH Zurich and the Swiss Federal Institute for Forest, Snow and Landscape Research WSL.

His research group at the Laboratory of Hydraulics, Hydrology and Glaciology (VAW) played a central role in producing the new findings. The entire study led by Zekollari and Schuster was conducted as part of the Glacier Model Intercomparison Project (GlacierMIP) and coordinated by the Climate and Cryosphere (CliC) Project of the World Climate Research Programme (WCRP).

Farinotti notes that the release of the Science study coincides with the opening of the High-Level International Conference on Glaciers’ Preservation, initiated by the President of Tajikistan through the United Nations (UN) Resolution that established both the UN Year of Glaciers’ Preservation and, later, the UN Decade of Action for the Cryospheric Sciences 2025-2034.

On the Swiss side, the Federal Department of Foreign Affairs (FDFA) was invited to support the organisation of the event, particularly in drafting what is intended to become the “Dushanbe Glacier Declaration.” Daniel Farinotti, for his part, is acting as an advisor to the FDFA in the preparation of the declaration.

The same was true 73 million years ago, according to a paper featured on the cover of this week’s edition of the journal Science. The paper documents the earliest-known example of birds nesting in the polar regions.

“Birds have existed for 150 million years,” said lead author Lauren Wilson, a doctoral student at Princeton University who earned her master’s degree at the University of Alaska Fairbanks. “For half of the time they have existed, they have been nesting in the Arctic.”

The paper is the result of Wilson’s master’s thesis research at UAF. Using dozens of tiny fossilized bones and teeth from an Alaska excavation site, she and her colleagues identified multiple types of birds — diving birds that resembled loons, gull-like birds, and several kinds of birds similar to modern ducks and geese — that were breeding in the Arctic while dinosaurs roamed the same lands.

Prior to this study, the earliest known evidence of birds reproducing in either the Arctic or Antarctic was about 47 million years ago, well after an asteroid killed 75% of the animals on Earth.

“This pushes back the record of birds breeding in the polar regions by 25 to 30 million years,” said Pat Druckenmiller, the paper’s senior author, director of the University of Alaska Museum of the North and Wilson’s advisor for her master’s degree work. The bird fossils are part of the museum’s collections.

“The Arctic is considered the nursery for modern birds,” he said. “It’s kind of cool when you go to Creamer’s Field [a Fairbanks-area stopover for migrating geese, ducks and cranes], to know that they have been doing this for 73 million years.”

The mere existence of the large collection of ancient bird fossils is remarkable, Wilson said, given how delicate bird bones are. That is doubly true for baby bird bones, which are porous and easily destroyed.

“Finding bird bones from the Cretaceous is already a very rare thing,” she said. “To find baby bird bones is almost unheard of. That is why these fossils are significant.”

The fossils were collected from the Prince Creek Formation, an area along the Colville River on Alaska’s North Slope known for its dinosaur fossils. Scientists identified more than 50 bird bones and bone fragments.

“We put Alaska on the map for fossil birds,” Druckenmiller said. “It wasn’t on anyone’s radar.”

The collection is a testament to the value of an uncommon excavation and research approach at the Prince Creek Formation. Much of vertebrate paleontology focuses on recovering large bones.

The scientists who work in the Prince Creek Formation make sure to get every bone and tooth they can, from the visible to the microscopic, Druckenmiller said. The technique, which involves hauling tubs of screened sediment back to the lab for examination under a microscope, has yielded numerous new species and unprecedented insights into the behavior and physiology of the dinosaurs, birds and mammals that lived in the Arctic during the Cretaceous Period.

“We are now one of the best places in the nation for bird fossils from the age of the dinosaurs,” Druckenmiller said. “In terms of information content, these little bones and teeth are fascinating and provide an incredible depth of understanding of the animals of this time.”

It remains to be seen whether the bones found on the Colville River are the earliest-known members of Neornithes, the group that includes all modern birds. Some of the new bones have skeletal features only found in this group. And, like modern birds, some of these birds had no true teeth.

“If they are part of the modern bird group, they would be the oldest such fossils ever found,” Druckenmiller said. Currently, the oldest such fossils are from about 69 million years ago. “But it would take us finding a partial or full skeleton to say for sure.”

Other collaborators on the paper include Daniel Ksepka from the Bruce Museum, John Wilson from Princeton University, Jacob Gardner from the University of Reading, Gregory Erickson from Florida State University, Donald Brinkman and Caleb Brown from the Royal Tyrrell Museum of Palaeontology and the University of Alberta (Brown is also affiliated with the University of Manitoba), Jaelyn Eberle from the University of Colorado Boulder and Chris Organ from Montana State University.

Leprosy is a neglected disease, mainly caused by the bacterium Mycobacterium leprae, affecting thousands of people worldwide: approximately 200,000 new cases of leprosy are reported each year. Although M. leprae remains the primary cause, this study focused on another species, Mycobacterium lepromatosis, discovered in the United States in 2008 in a Mexican patient, and later in 2016 in red squirrels in the British Isles. Led by scientists from the Laboratory of Microbial Paleogenomics at the Institut Pasteur, also associated with the CNRS, and the University of Colorado, in collaboration with Indigenous communities and over 40 scientists from international institutions including archaeologists, this study analyzed DNA from nearly 800 samples, including ancient human remains (from archaeological excavations) and recent clinical cases presenting symptoms of leprosy. The results confirm that M. lepromatosis was already widespread in North and South America long before European colonization and provide insights into the current genetic diversity of pathogenic Mycobacteria.

“This discovery transforms our understanding of the history of leprosy in America,” said Dr. Maria Lopopolo, the first author of the study and researcher at the Laboratory of Microbial Paleogenomics at the Institut Pasteur. “It shows that a form of the disease was already endemic among Indigenous populations well before the Europeans arrived.”

The team used advanced genetic techniques to reconstruct the genomes of M. lepromatosis from ancient individuals found in Canada and Argentina. Despite the geographic distance of several thousand kilometers, these ancient strains dating from similar periods (approximately 1,000 years ago) were found to be surprisingly genetically close. Although they belong to two distinct branches in the evolutionary tree of the genus Mycobacterium, these branches are genetically closer to each other than to any other known branch. This genetic proximity, combined with their geographical distance, necessarily implies a rapid spread of the pathogen across the continent, likely within just a few centuries.

The scientists also identified several new lineages, including an ancestral branch that despite having diverged from the rest of the known species’ diversity over 9,000 years ago, it continues to infect humans today in North America — a discovery suggesting an ancient and long-lasting diversification on the continent, as well as a largely unexplored diversity that likely remains to be found.

Notably, the analyses also suggest that the strains found in red squirrels in the UK in 2016 are part of an American lineage that was introduced to the British Isles in the 19th century, where it subsequently spread. This discovery highlights the recent ability of the pathogen to cross continents, likely through human or commercial exchanges.

“We are just beginning to uncover the diversity and global movements of this recently identified pathogen. The study allows us to hypothesize that there might be unknown animal reservoirs,” said Nicolás Rascovan, the lead author of the study and head of the Laboratory of Microbial Paleogenomics at the Institut Pasteur. “This study clearly illustrates how ancient and modern DNA can rewrite the history of a human pathogen and help us better understand the epidemiology of contemporary infectious diseases.”

The project was conducted in close collaboration with Indigenous communities, which were involved in decisions regarding the use of ancestral remains and the interpretation of results. Ancient DNA and remaining materials were returned when requested, and the generated data was shared via ethical and adaptable platforms designed to allow data sharing that meets the specific expectations of Indigenous communities.