The 17th century Dominican Church of the Holy Spirit is one of the oldest in Vilnius, Lithuania. Tourists and parishioners come to marvel at its Baroque façade, pillars and priceless paintings. However, its dark crypt was the real draw for an international team of researchers. The crypt houses thousands of naturally mummified corpses along with a wealth of information on the diseases that claimed their lives.
Now a study of one child mummy’s DNA has uncovered the oldest sample of the smallpox-causing variola virus and could rewrite the history of one of the world’s most devastating diseases.
The image shows a mummy discovered through collaboration with the Lithuanian Mummy Project in 2015. Samples from this mummy were found to house degraded samples of Variola, the virus that causes smallpox. (Credit: Kiril Cachovski of the Lithuanian Mummy Project, 2015)
Hendrik Poinar, a senior fellow in the Humans & the Microbiome program and evolutionary geneticist (McMaster University), studies infectious disease via ancient DNA. He was looking for a relatively benign virus that can be used as a surrogate for human migrations in the mummy remains but realized his team had stumbled across something more remarkable.
“Data jumped out in sequences that looked like variola” he recalls during a Facebook Live discussion.
“We were surprised by that, because there are no pox-like impressions on the mummy itself. There was no suggestion that this mummy died of smallpox.”
The fact that the variola virus didn’t exhibit symptoms is interesting for historians, Poinar says. They can now re-examine certain remains given the possibility of “hidden” diseases.
Poinar’s team traced the lineage of smallpox by recreating the full genome of the 17th century smallpox virus. They began by collecting total DNA from the mummy’s soft tissue. Next, they designed an RNA bait set, using existing variola viral sequences in-silico, that acted as a “fishing line” to target the virus specifically from the soup that contained human, bacterial, fungal and viral DNA. They then pieced together the genome bioinformatically so that they could analyze it in comparison to the ‘modern’ strains in the database (1944-1977). Both 17th century and 20th century genomes appear to share an ancestor that originated sometime between 1588 and 1645, very close to the date of the mummy.
The findings suggest smallpox may have emerged in humans much earlier than previously thought. It also casts doubt on the validity of cases dating back to pharaoh Ramses V, who reportedly died in 1145 B.C. with pox-like lesions on his face.
The image shows the crypt in a church in Lithuania where researchers uncovered a child mummy that carried the oldest known samples of variola, the virus that causes smallpox. (Credit: Kiril Cachovski of the Lithuanian Mummy Project, 2015)
Sequencing the variola genome also sheds light on the recent history of smallpox. The child mummy was carbon dated to between 1643 and 1665, shortly after an outbreak in London and around the time when many epidemics spread across Europe. The genome shows the virus evolved into a minor and major strain before it was “eradicated” through vaccination in 1980.
“Will variola re-emerge? Well, it’s always possible and having a better understanding of its origins … seems like a prudent thing to do,” Poinar says.
Another recent paper by Poinar on the detection of malaria during the Roman Empire raises similar questions. The study includes the first genomic data linking malaria to adults in Italy during this time. Researchers employed the RNA baits method to detect Plasmodium falciparum, the parasite that causes malaria. This has led some to ask if malaria could have contributed to the downfall of the Roman Empire, but Poinar says much more research is needed.
“There are still millions of questions, so now we need to push back further in time,” he says.
“17th Century Variola Virus Reveals the Recent History of Smallpox” was published in Current Biology Dec. 8. “Plasmodium falciparum malaria in 1st–2nd century CE southern Italy” was published in Current Biology Dec. 5.