In the Middle Ages, in what is now northern Kyrgyzstan, there was a bustling settlement called Kara-Djigach on a trade route known as the Silk Road.
But in AD 1338, the community was hit by an unknown plague that filled the cemetery with fresh graves. Some of the tombstones recorded the cause of death as "pestilence."
Flash forward to today and researchers have used ancient DNA to pinpoint these deaths as among the earliest cases of the most devastating outbreak of bubonic plague.
"The Black Death is arguably the single harshest killer of humans in all recorded history," said Philip Slavin from the University of Stirling in Scotland, co-author of new research published in the journal Nature.
The pandemic is estimated to have claimed the lives of up to 60 per cent of the western Eurasian population over eight years from 1346, writes Dr Slavin and colleagues.
But while it is believed to have come to Western Europe from further east, arguments on exactly where it originated have raged for centuries.
"The Black Death has been one of the most debated topics in history," said Dr Slavin, a historian with an interest in environmental disasters and disease.
But in 2011, scientists fully sequenced the genome of the plague-causing bacterium, Yersinia pestis.
And this meant researchers could go looking for hard genetic evidence of the microbe in human remains.
Dr Slavin and colleagues focused on remains from cemeteries located north-west of Lake Issyk-Kul in Kyrgyzstan, not far from the mighty Tian Shen mountains.
In studying records, Dr Slavin noticed a "massive spike" in the number of annual burials in the area between 1338 and 1339 and wondered whether there might be a link to the outbreak of the Black Death soon after.
Archaeologists who had originally excavated the cemeteries in the 19th century had carefully matched hundreds of tombstones, complete with dates and epitaphs, with what was found beneath them.
"All that was missing was the ancient DNA," Dr Slavin said.
Researchers turn to some very old teeth
Dr Slavin teamed up with geneticists at the Max Planck Institute in Germany to look for DNA of plague-causing bacteria in the teeth of a handful of people who died at the time.
Three of seven specimens came back positive for Y. pestis, confirming the plague was to blame.
Then the researchers compared the sequence of the bacterial genome to others on file to map the relationship between them on a family tree.
This gave them a picture of the spread of the plague - like when we use genomic contact tracing to work out the movement of coronavirus through time and space.
One of the genomes used for comparison came from bacteria the researchers previously isolated, from a sample further west, in the Volga region in Eastern Europe.
Until now that was the oldest genomic evidence of Black Death, but the Kyrgyzstan sequence is ancestral to the one from Volga, so confirms Central Eurasia as the origin of the pandemic.
"What's really amazing is its position [in the family tree] shows that it came right before the Black Death," Dr Slavin said.
A language specialist on the team helped translate other information that also supported the presence of the plague, including tombstones that recorded the cause of death as "pestilence".
'Pretty remarkable'
Australian infectious diseases expert Eddie Holmes was impressed by the research.
"That they were able to find these ancient plague samples was pretty remarkable," said Professor Holmes from the University of Sydney.
"The key thing about this paper is not just where it (the plague) appeared, but when it appeared."
In particular, he points to the fact the disease arose in the Tian Shen area just a matter of years before the Black Death was first reported as a major pandemic.
"The bacteria from these victims was ancestral to all later strains, meaning that it was the point of origin.
"It's a bit like finding the first cases of Covid-19 in Wuhan."
He said the bacteria probably jumped from rodents into humans in the Tian Shan region, before spreading to Western Europe via the ancient trade routes.
In the 14th century, the urban settlement of Kara-Djigach was a stop on the Silk Road linking China with the Middle East, Africa and Europe.
Dr Slavin said the cemetery excavation found stashes of coins from as far away as Iran and northern Afghanistan, pearls that must have come from the Indian or Pacific Oceans, corals, shells, and silk.
Narrow margin for error?
Jeremy Austin of the Australian Centre for Ancient DNA at the University of Adelaide said the dated tombstones were a "fantastic" opportunity to link the plague with specific dates and locations.
"It's a fine story and it's probably a good interpretation," Dr Austin said.
But he was concerned about what he saw as a narrow margin for error.
"The whole story hangs on the fact that the genome that they analyse is right at the very base of the phylogenetic tree of Y. pestis that went on to cause the Black Death."
But he said there was very little difference between the sequence of the bacteria retrieved from Kyrgyzstan, and the Volga sample from further west.
He said this meant any mistakes in sequencing could undermine the researchers' conclusions.
"If they've made two sequencing errors, their sample moves up the tree."
And this, Dr Austin said, could change the story about the direction and spread of the Black Death.
Patient zero for the Black Death?
If the genetics are right, this would be the closest so far scientists have come to finding patient zero for the Black Death.
So, are we likely to ever find the very first case?
Professor Holmes doubts it, describing the idea as an "almost mythical entity."
"We almost never, ever detect patient zero.
"But in this case, patient zero would have only have existed a few years before the human remains sampled here."
It is possible patient zero could have been a nomad or another traveller, although there is no evidence either way.
"Who knows? But they would have definitely have interacted with an infected rodent," Professor Holmes said.
"It's amazing that ancient DNA puts us this close."
- ABC