Oldest known evidence of plague reveals the disease’s deadly impact 5,500 years ago
By Ashley Strickland, CNN
(CNN) — Ancient DNA recovered from cemeteries in southeast Siberia has revealed previously unknown strains of plague that had a deadly impact on an unexpected group of people 5,500 years ago.
The early plague strains, detailed in a new study published Wednesday in the journal Nature, may be the oldest known evidence of the disease in humans.
Plague is caused by the bacterium Yersinia pestis and has led to some of the most devastating disease outbreaks in human history, including the infamous Black Death in the 14th century, which killed an estimated 25 million people over five years. Before the discovery of the newly identified strain, some of the earliest known strains of Yersinia pestis associated with bubonic plague had been dated to about 3,800 years ago.
Previously, older strains appeared to lack the genetic traits that enabled them to spread, leading scientists to think that early plagues were unlikely to trigger outbreaks. With sparse evidence of other lethal precursors of the disease, scientists questioned when and where the bacterium originated before it spread from early livestock such as sheep and infected fleas to humans.
The newly discovered strain almost immediately seemed to add a twist to the story. Researchers came across it while they were trying to solve another puzzle in the remains of hunter-gatherers buried in cemeteries of the Lake Baikal region. Two of the largest cemeteries contained an unusually large number of children and young adolescents whose remains lacked any trauma or apparent cause of death.
An analysis of ancient DNA within the remains revealed the unexpected presence of plague bacteria in 18 of 46 individuals from the small, mobile communities — as well as a genetic factor that might have increased the infection’s severity.
The findings add to growing evidence that suggests where plague might have originated, experts say — and also challenge ideas about what enabled plague to spread.
“Hunter-gatherers are constantly moving around the landscape,” said lead study author Ruairidh Macleod, a research fellow at the UK’s University of Oxford, during a news conference Tuesday to discuss the results.
“The theory is that infectious disease can’t really take hold and devastate entire communities in this way. Typically, if somebody gets ill, they’ll move somewhere else. The fact that we’re finding this happening in an isolated group of prehistoric hunter-gatherers challenges that epidemiological theory.”
An unexpected outbreak
Archaeologists have excavated the four ancient cemeteries around Lake Baikal for decades. The region was rich in resources, including waters for fishing, and the cemeteries show that the hunter-gatherers buried their dead nearby for generations — perhaps to claim the region for themselves, Macleod said.
The study authors combined advanced DNA sequencing of genetic material, in-depth archaeological research and radiocarbon dating to paint a complete picture of what took place in the region thousands of years ago.
“There was very clear radiocarbon evidence that this mass mortality event took place over a very, very short period of time,” Macleod said, “so all of these deaths are occurring contemporaneously with each other.”
Genetic research shed light on the kinship between children and adults buried in the cemeteries.
Sometimes, siblings, parents and children were buried together, suggesting the disease passed from one family member to another as they cared for one another — and a lack of understanding for how the disease spread, said study coauthor Eske Willerslev, evolutionary geneticist and professor at Denmark’s University of Copenhagen and the UK’s University of Cambridge.
Other graves showed relatives who were buried apart, presumably because they died during different waves of the disease, according to the study. Two outbreaks are believed to have occurred a few hundred years apart in the region, the study found.
“The authors are able to detect probably Y. pestis infections at a rate of 39% across the cemeteries investigated — this is astoundingly high and certainly has the potential to rewrite how we understand early infections of the pathogen,” said Ian Light-Maka, postdoctoral associate at the Max Planck Institute for Infection Biology in Berlin.
“Previous research has only found what seem to be sporadic, relatively isolated infections of the earliest versions of Y. pestis with no compelling evidence of human-to-human transmission chains, but the datasets may have simply been too incomplete to assess this as a possibility. This study changes that.”
Light-Maka, who was not involved with the study, also cautioned that while human-to-human transmission was likely, further research at different sites during the time period is needed to confirm it.
The researchers were able to extract ancient bacterial genomes from teeth, which suggest that the unique plague strain originated 5,700 years ago. It is different from other known plague strains, both ancient and modern, the researchers said.
The genomes also revealed a unique superantigen, or a microbial toxin that can increase an infection’s severity and activate extreme immune responses — one that appears to have predominantly affected children between the ages of 7 ½ and 11 years old.
“A really poignant example is this grave where we see three very young girls having presumably died at the same time,” Macleod said. “It’s clearly having a very tragic impact on the children, in particular, in the communities.” The girls were cousins, and two were siblings, the youngest being 4 or 5 and the oldest likely 9 years old.
“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 study author Martin Sikora, population geneticist and associate professor at the University of Copenhagen.
The superantigen is also present in modern-day Yersinia pseudotuberculosis, an infection that naturally occurs in animals. Humans can contract it from eating raw or undercooked contaminated food or untreated drinking water, an association that may offer clues to the plague’s earliest mode of transmission as well.
Tracing how plague spread
So how did the hunter-gatherers become infected in the first place? It was likely through large rodents called marmots, the study authors determined, which have a deep evolutionary history of carrying the bacteria that causes plague. Marmots remain a primary species in the region that can still cause plague cases.
The plague victims likely hunted, skinned and butchered marmots for their meat and fur, which would have exposed members of the community to the bacteria, Macleod said. Marmot teeth pendants were also found within the graves.
“We believe that marmots are the oldest reservoir species of plague,” Macleod said. “This is consistent with a hypothesis that plague originated in this part of the world.”
Some researchers believe that plague originated in Central or Northeast Asia before spreading across Eurasia — long before the rise of agriculture, dense populations or crowded cities associated with later outbreaks, the study authors said.
“This research illustrates the vast complexity of ancient plague ecology by showing in detail how zoonotic diseases ravaged more than farming cultures,” said Dr. Taylor Hermes, assistant professor in the department of anthropology at the University of Arkansas. Hermes has researched ancient plague transmission across Central Asia but was not involved in this study.
“It echoes how other life ways, be that hunter-gatherer or nomadic pastoralist, played major roles in disease evolution through their vital yet sometimes deadly relationships with animals,” Hermes wrote in an email.
But many mysteries endure about plague, including how it spread across Northern Eurasia so quickly.
“After the outbreak in the Baikal hunter-gatherers who are both culturally and genetically isolated from non-hunter-gatherer populations, it appears in Northern Europe only 200-300 years later,” Macleod wrote in an email. “Did this happen by really rapid transmission through wild animals, from spillover infections into humans at either end? How much was human-to-human transmission involved?”
Tracing plague’s ancient path is crucial to understand how pathogens evolve over time — especially given that plague cases still occur each year, Willerslev said.
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