MILAN, Italy — Smallpox hasn’t been a health concern since around the 1970s, which is when doctors recorded the last known natural case in Somalia. Before then, however, smallpox was among humanity’s most devastating and deadly diseases. In just the 20th century alone, the disease killed at least 300 million people before the World Health Organization declared it “eradicated” in 1980. Now, new findings show the smallpox virus is even older than scientists believed — dating back 2,000 years further than previously established.
Study authors say their work confirms the smallpox virus has been plaguing human societies since the age of ancient civilizations. Technically, smallpox is caused by the variola virus. Up until a few years ago, the earliest genetic evidence of smallpox was only from around the 1600s. That all changed in 2020 when a study that sampled both the skeletal and dental remains of Viking-age skeletons detected multiple variola strains, thus confirming the smallpox virus’s existence at least 1,000 years earlier.
Many historians, however, believe smallpox existed long before the Viking age. Suspicious scarring observed on ancient Egyptian mummies (including the Pharoah Ramses V who died in 1157 BC) has led some scientists to speculate the history of smallpox stretches back at least 3,000 years — if not longer.
Scientists find smallpox’s ancient ancestor
Now, by comparing the genomes of both modern and historic strains of the variola virus, scientists at the Scientific Institute Eugenio Medea and University of Milan have successfully traced the virus’ evolution back in time. They report different smallpox strains all descended from a single common ancestor. A small portion of the genetic components found in Viking-age genomes then persisted until the 18th century.
Study authors also estimated when the virus may have truly originated. While performing these calculations, researchers were sure to consider something called the time-dependent rate phenomenon, which refers to the speed of evolution depending on the length of time scientists are measuring. Consequently, viruses often appear to change more quickly over a shorter timeframe and more slowly over a longer timeframe. Prior studies have documented this phenomenon among DNA viruses like variola.
Using a mathematical equation, researchers can now account for the time-dependent rate phenomenon, providing more accurate dates for evolutionary events like the emergence of a new virus. All in all, this approach provided the research team with a new estimate for the first emergence of smallpox — over 3,800 years ago.
Study authors hope this work will help settle a longstanding historical and scientific debate, all while also providing some much-needed insight into the history of one of humanity’s deadliest diseases.
“Variola virus may be much, much older than we thought,” says Dr. Diego Forni, first author of the study, in a media release. “This is important because it confirms the historical hypothesis than smallpox existed in ancient societies. It is also important to consider that there are some aspects in the evolution of viruses that should be accounted for when doing this type of work.”
The study is published in the journal Microbial Genomics.