Smallpox, caused by the variola virus, is one of the worst diseases humanity has ever faced, and it has many distinctions. The first vaccine that was ever developed was for smallpox, for example. It likely killed 300 million people or more before it was eliminated from circulation in an intensive campaign by the World Health Organization (WHO) and other institutions that began in 1967. The last known naturally occurring case happened in 1977 in Somalia. It is the only disease that humans have been able to completely eradicate.
The origins of smallpox are still a mystery. Historical records have suggested that smallpox has been affecting people for 3,500 years, while archaeovirology studies have indicated that the virus has been around for about 1,700 years.
A new study has now estimated that the variola virus emerged 3,800 years ago or more, and that it did infect people living in ancient societies. Pockmarks on Egyptian mummies support this claim. In this study, researchers compared the genomes of modern and historic variola strains, tracing the evolution of the virus through time. The work showed that different viral strains have evolved from a common ancestor. The findings have been reported in Microbial Genomics.
In 2020, a study of skeletons from the Viking era revealed genetic material from several variola virus strains. Previous genetic evidence had only dated the virus to about the year 1600, so the 2020 research showed that smallpox was circulating at least 1,000 years before that.
The researchers have also speculated about when the virus emerged. In viruses, there is a known evolutionary feature known as a "time-dependent rate phenomenon." The rate of viral evolution depends on the timeframe that's being considered; viruses will appear to change more rapidly in short time spans, and more slowly over long periods. The study authors accounted for this, and created an equation that allowed them to make an estimate, which agrees with historians that the virus emerged over 3,800 years ago. The scientists are hopeful that a controversy in these fields will now be resolved.
There are two main lineages of variola, which split from the ancestor prior to the development of a vaccine; these lineages seem to have arisen at a time when human population was increasing dramatically.
The researchers also suggested that the virus likely emerged in Africa or the Middle East. It may have originated in gerbils, who harbor the likely ancestor of smallpox, and the pockmarked mummies provide evidence of smallpox in Ancient Egypt.
"Variola virus may be much, much older than we thought. This is important because it confirms the historical hypothesis that 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," noted first study author Dr. Diego Forni of the Eugenio Medea Scientific Institute (IRCCS E. Medea).
Sources: Microbiology Society, Microbial Genomics
