This Deadly Disease Was Wiping Out Humans 5,500 Years Ago

A new study suggests plague was already a deadly threat 5,500 years ago, striking small hunter-gatherer communities long before cities and agriculture emerged.

For centuries, plague has been remembered as the disease that devastated medieval Europe, killing millions and reshaping societies. But new research suggests its deadly history stretches much further back than previously thought.

A study published in Nature has uncovered evidence that plague was already causing fatal outbreaks 5,500 years ago among small hunter-gatherer groups in Siberia. The discovery challenges the long-held idea that plague only became a major threat after the rise of agriculture, dense settlements, and the rat-infested urban environments that later fueled historic pandemics.

An international team of researchers analyzed ancient DNA from human remains buried at four hunter-gatherer cemeteries near Lake Baikal in eastern Siberia. By extracting and sequencing bacterial DNA preserved inside teeth, they reconstructed some of the oldest known genomes of Yersinia pestis, the bacterium responsible for plague.

The findings reveal that these ancient strains were far from harmless.

"Whether the earliest forms of plague were mild or virulent has been a matter of debate, but our findings demonstrate that these ancient strains were already highly lethal," said senior author Eske Willerslev, a professor at the University of Copenhagen and the University of Cambridge.

Reconstructing a prehistoric outbreak

Ancient DNA studies can reveal whether an individual carried a disease, but this project went much further. Researchers combined genetic evidence with radiocarbon dating, burial records, and family relationships preserved in DNA to reconstruct how the outbreaks unfolded within these prehistoric communities.

"Based on the plague DNA, the genetic relationships between the victims, the archaeological analysis and the radiocarbon dating, we've built a really clear, complete picture of what happened during these outbreaks," said lead author Ruairidh Macleod, who conducted the research while a PhD student at the University of Cambridge and is now a research fellow at the University of Oxford.

The team detected Yersinia pestis DNA in 18 of the 46 individuals examined, nearly 40% of those tested. That proportion is strikingly high and exceeds rates reported from some medieval plague burial sites.

A decades-old mystery finally solved

One of the strongest clues came from the cemeteries themselves.

For years, archaeologists were puzzled by an unusually large number of children and young teenagers buried at two of the sites. Unlike normal mortality patterns expected in hunter-gatherer populations, the graves appeared to reflect a sudden event that disproportionately affected younger individuals.

"The unusually high number of children and the short timespan was a real puzzle that we've been trying to solve since the 1990s. Finding out that plague was the cause is extraordinary, but it makes so much sense," said archaeologist Andrzej Weber of the University of Alberta and principal investigator of the Baikal Archaeology Project.

Radiocarbon dating revealed that many of the deaths occurred within a relatively short period. In some cases, close relatives, including siblings and parents with children, appear to have died around the same time and were buried together. Such patterns are often associated with infectious disease outbreaks.

Why was this early plague so deadly?

The discovery is surprising because these ancient strains lacked several genetic adaptations that later helped plague spread efficiently through fleas and rodents, the transmission route behind the infamous Black Death and other historical pandemics.

Because those traits were missing, many researchers assumed the earliest versions of plague were less dangerous.

Instead, the new study points to another possible explanation for their lethality.

The ancient strains carried a unique superantigen, a toxin-producing genetic factor absent from later plague lineages. Superantigens can trigger an overwhelming immune reaction, causing severe inflammation and potentially life-threatening complications.

"This finding changes our understanding of the earliest plague outbreaks: Even before the bacterium evolved efficient flea-borne transmission, these ancient strains appear to have carried a potent combination of virulence factors that could make infection highly lethal," said senior author Martin Sikora, an associate professor at the University of Copenhagen.

Clues to plague's ancient origins

The results suggest that some of the earliest known plague outbreaks may have been just as deadly as later historical epidemics, particularly for children, despite lacking flea-borne transmission.

The study also supports the idea that plague originated in Central or Northeast Asia before spreading across Eurasia through wild rodent populations. Archaeological evidence indicates that these hunter-gatherers had close contact with marmots, large burrowing rodents that still carry plague today. Researchers believe the disease may have passed directly from infected marmots to humans.

Reference: "Lethal plague outbreaks in Lake Baikal hunter-gatherers 5,500 years ago" by Ruairidh Macleod, Frederik V. Seersholm, Bianca De Sanctis, Angela Lieverse, Adrian Timpson, Rick Schulting, Jesper T. Stenderup, Charleen Gaunitz, Lasse Vinner, Olga Ivanovna Goriunova, Vladimir Ivanovich Bazaliiskii, Sergei V. Vasilyev, Erin Jessup, Yucheng Wang, Christopher Bronk Ramsey, Mark G. Thomas, Russell Corbett-Detig, Astrid K. N. Iversen, Andrzej W. Weber, Martin Sikora and Eske Willerslev, 17 June 2026, Nature.
DOI: 10.1038/s41586-026-10540-5