At least 300 million individuals lost their lives to smallpox in the twentieth century, leaving an indelible impact on human history. Even with all the attention the virus has received, its history is still a mystery.
By corroborating historical records that showed the illness has afflicted human cultures since the time of the pharaohs, a team of Italian scientists has now moved our best estimates for the origin of smallpox back by another 2,000 years. Researchers have come closer to understanding the origins of smallpox as they have been able to conduct more in-depth investigations of ancient viral DNA thanks to advances in genetic sequencing technology.
Archaeovirology efforts provided a rich portrait of the evolutionary history of variola virus (VARV, the cause of smallpox), which was characterized by lineage extinctions and a relatively recent origin of the virus as a human pathogen
Using viral DNA extracted from a young boy’s bones, researchers in Lithuania in 2016 were able to track smallpox back to the 1500s. Genetic evidence for the most recent smallpox outbreak was moved back a few years, to before 1050 CE, in 2020 thanks to virus DNA from Viking Age bones.
However, there is evidence from the past that a disease similar to smallpox ravaged ancient communities far earlier in human history. Chinese manuscripts from the 4th century describe symptoms that are consistent with smallpox, and pockmark scarring on Egyptian mummies from that time period also suggests that smallpox was common in that region.
However, molecular fingerprint-style genetic data, suggesting that a particular virus is responsible, has remained elusive.
By comparing enough samples, scientists may still learn a lot about the origins and development of a virus. Through studying viral evolution, scientists can determine how quickly or slowly a virus acquires new genetic changes. Scientists may then use this information to “wind the molecular clock back” to determine when a precursor virus likely existed.
The variola virus, abbreviated VARV, is responsible for triggering smallpox infections. This new study was directed by bioinformatician Diego Forni of Italy’s Scientific Institute for Research, Hospitalization, and Healthcare (IRCCS), who oversaw a team that reexamined the genetic sequences of 54 VARV samples culled from prior studies or a database.
There were 48 current VARV sequences from before smallpox was eliminated in 1980, in addition to 4 ancient VARV genomes dating back to the Viking Age as well as 2 historic VARV genomes from the 17th&18th centuries.
Using these viral sequences, researchers were able to recreate the smallpox virus’s evolutionary history, revealing how the virus split from a single common parent into many subtypes that either expanded widely or died out.
Their models accounted for the fact that the pace of viral evolution appeared to decrease when considering more extended periods of time but to quicken when considering more condensed ones. They determined that the common ancestor of all VARV genomes occurred around 3,800 years ago.
The investigation also revealed that the smallpox virus progenitor diverged from its cousins roughly 7,700 years ago, when comparing the VARV genomes to those of two related orthopoxviruses, taterapox (which affects gerbils) and camelpox.
Researchers think that this still provides a rather large window for when smallpox may have crossed over into humans, anywhere from around 8,000 to 4,000 years ago. Nonetheless, the results add to the mounting body of evidence that smallpox has been with humanity for millennia longer than had been anticipated by prior examinations of viral DNA samples.
There is still considerable doubt as to whether or not smallpox was common back then, despite the fact that these new dating estimations place the illness in the appropriate period to fit historical descriptions of Egyptian pharaohs exhibiting smallpox scars.
