Until relatively recently, the earliest genetic evidence for the deadly viral disease smallpox was from the 1600s. Then in 2020, a study that sampled skeletal and dental remains of Viking-age skeletons recovered multiple strains of variola and confirmed the virus’s existence at least a millennium earlier.
Humans were the only known host of variola virus, but the timeframe of its emergence in our species has been a matter of debate. Some historians believed that smallpox – one of humanity’s most devastating scourges – has been around since long before the Vikings.
Suspicious scarring on ancient Egyptian mummies – including Pharaoh Ramses V, who died in 1157 BCE – leads some to believe that the history of smallpox stretches back at least 3,000 years. That means when the ancient Israelites were slaves in Egypt, the disease caused by the variola virus already existed.
So far, the missing piece of scientific evidence to support this theory has remained hidden. Now, by comparing the genomes of modern and historic strains of the variola virus, researchers at the Scientific Institute Eugenio Medea and University of Milan in Italy have traced its evolution back in time. They found that different strains of smallpox all descended from a single common ancestor and that a small fraction of the genetic components found in Viking-age genomes had persisted until the 18th century.
The research appears in the peer-reviewed journal Microbial Genomics, published by the Microbiology Society, titled “Analysis of variola virus molecular evolution suggests an old origin of the virus consistent with historical records.”
What is the history of smallpox?
Smallpox is perhaps best known for being the only infectious human disease to be eradicated worldwide. However, it was a major cause of death until relatively recently, killing at least 300 million people in the 20th century, which is close to the population of the US.
Smallpox vaccination was pioneered by English Doctor Edward Jenner in 1796, when he noticed that milkmaids who had gotten cowpox were protected from smallpox. Jenner also knew about variolation – the early form of inoculation – and guessed that exposure to cowpox could be used to protect against smallpox.
Although vaccination spread rapidly, the disease was still endemic in Europe and in many other areas at the end of the 19th century. But intensification of the vaccination campaign during the 20th century led to the eradication of smallpox in 1980.
The researchers also worked out an estimate for when the virus originated. In their estimate, they accounted for something called the “time-dependent rate phenomenon.” This means that the speed of evolution depends on the length of time over which it is being measured, meaning that viruses appear to change more quickly over a short period and more slowly over a longer period. The phenomenon has been well-documented in DNA viruses such as variola.
Using a mathematical equation, scientists can account for the time-dependent rate phenomenon to give more accurate dates for evolutionary events, such as the appearance of a new virus. This gave the team a new estimate for the first emergence of smallpox – more than 3,800 years ago, as historians have long suspected.
The researchers hope these findings will settle a longstanding controversy and provide new insight into the history of one of humanity’s deadliest diseases.
“Variola virus may be much, much older than we thought.”Dr. Diego Forni
“Variola virus may be much, much older than we thought,” said Dr. Diego Forni, the first author of the study. “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.”