Sheeppox is a highly contagious, often fatal viral disease that was largely eradicated from much of European livestock in the 20th century. But there is still the occasional regional outbreak, such as the one that afflicted many flocks of sheep in Greece last year. In order to reconstruct how the virus has evolved over the last 3,500 years, scientists extracted and sequenced sheeppox DNA preserved in the animal skins used for the parchment of numerous medieval manuscripts. They reported their findings in a new paper published in the journal Science Advances.
“The recording of ancient DNA of pathogens has completely changed our understanding of infectious disease in the past, and here we show that parchment can also preserve animal pathogen DNA. It is possible that archives and libraries around the world also contain the genetic traces of disease outbreaks in animals in the past,” said co-author Louis L’Hôte, a graduate student at University College Dublin. “These genomes help us understand how these pathogens evolved and how they impacted past societies—such as sheeppox virus, which we show has been affecting Eurasian sheep herds for at least three and a half millennia.”
Per the authors, the earliest known written evidence of sheeppox infection dates to the first century CE, when Roman accounts described outbreaks of skin lesions (“pustules”) in the animals. There are more frequent mentions of deadly outbreaks of “pockes” or “variola” in sheep by the Middle Ages, recorded in various agricultural texts and accounting documents in France, Spain, and England. There seemed to be a decline in outbreaks in 17th-century France, although frequent outbreaks re-emerged in the 18th and 19th centuries, often with high mortality rates in the flocks. Great Britain did not experience a sheeppox resurgence until 1847.
However, very little was known about the genetic history of the sheeppox virus. That’s why L’Hôte et al. turned to analyzing DNA in medieval manuscripts—the parchments were often made from sheep leather. A number of analytical techniques have emerged in recent decades to help create these kinds of historical molecular records.
For instance, last year we reported on research that used microbial DNA analysis of human remains to identify the likely pathogens that killed many soldiers in Napoleon’s army in 1812. Two pathogens in particular stood out: Salmonella enterica, which causes paratyphoid fever, and Borrelia recurrentis, which is transmitted by body lice and causes relapsing fever. Both are consistent with written contemporary accounts.
Evolution of a virus
The team collected samples from medieval manuscripts housed in collections at Yale University, Cambridge University, Corpus Christi College, University College Dublin, the Lambeth Palace Library, and Trinity College, among others. Those works included pages from a 15th-century Speculum Historiale; the 15th-century Clairvaux manuscripts; several 9th-century gospel text fragments; the 9th-century Achadeus Psalter; the early 11th-century Trinity Gospels; the Lambeth Bible; and the 1,000-year-old York Gospels.
Multiple pages, often from the same manuscript, were found to contain DNA from the sheeppox pathogen, which means infected animals were likely used to make the parchment—and thus, that medieval flocks experienced frequent outbreaks of sheeppox. The authors were surprised when they also found evidence of the sheeppox virus on parchment made from calfskin and goatskin, suggesting either cross-species infection or contamination when the parchment was being made.
The team also extracted DNA from Bronze Age sheep teeth collected at settlement sites in Russia and Central Kazakhstan, since teeth can preserve DNA evidence of infection over thousands of years. After comparing those ancient sequences with the medieval ones, the authors concluded that the sheeppox virus diverged from the goatpox and lumpy skin disease viruses (all members of the Capripoxvirus family) between 11,500 and 3,700 years ago. That coincides roughly with the domestication of animals in Europe. All told, the team recovered 21 ancient genomes from 1700 BCE to early modern Europe.
“Parchment making has been considered a vanishing craft, but we are beginning to understand just how much of the past it has retained,” said co-author Kevin G. Daly, also of UCD. “This project shows that parchments not only preserve our cultural history for hundreds of years, but also the landscape of disease in our livestock in the medieval period. This kind of exciting, surprising discovery is only possible when researchers from a range of disciplines come together to share their expertise and data—a generosity and trust that collaborative science depends on.”
Science Advances, 2026. DOI: 0.1126/sciadv.aeh3571 (About DOIs).
