One of humanity’s deadliest diseases is much older than we think

Small­pox has left an unmis­tak­able mark on human his­to­ry, killing at least 300 mil­lion peo­ple in the 20th cen­tu­ry alone. Although this virus is well-known, its ori­gin is still unknown.

A team of Ital­ian sci­en­tists has now pushed pre­vi­ous esti­mates of small­pox out­breaks for­ward by 2,000 years, adding his­tor­i­cal evi­dence that sug­gests the dis­ease has plagued human soci­ety since ancient times, when pharaohs ruled. I ver­i­fied it.

In recent years, advances in gene sequenc­ing tech­nol­o­gy have enabled us to ana­lyze frag­ments of ancient viral DNA in greater detail, bring­ing us clos­er to when and where small­pox originated.

Thanks to a lucky dis­cov­ery in Lithua­nia in 2016, sci­en­tists were able to trace small­pox to the 16th cen­tu­ry using viral DNA extract­ed from the remains of chil­dren. In 2020, viral DNA from Viking-era skele­tons pushed the last appear­ance of small­pox back sev­er­al years, to some­time before 1050 AD, pro­vid­ing genet­ic evidence.

How­ev­er, his­tor­i­cal sources sug­gest that some­thing like small­pox struck ancient soci­eties much ear­li­er. There are descrip­tions of dis­ease-like symp­toms in 4th-cen­tu­ry Chi­nese writ­ings, and small­pox-marked Egypt­ian mum­mies also sug­gest an epi­dem­ic of small­pox 3,000 to 4,000 years ago.

But find­ing defin­i­tive genet­ic evi­dence (like a viral mol­e­c­u­lar fin­ger­print) to sup­port this the­o­ry has been difficult.

With enough sam­ples to com­pare against, sci­en­tists can still infer a lot about the past and evo­lu­tion­ary his­to­ry of virus­es. You can see how virus­es have changed over time, and how fast or slow their genes mutate. From there, sci­en­tists can unwind the ‘mol­e­c­u­lar clock’ and deduce when the ances­tral ver­sion of the virus existed.

Small­pox is caused by the var­i­o­la virus (VARV). In this study, led by Diego Forni, a bioin­for­mati­cian at the Sci­en­tif­ic Insti­tute for Research, Hos­pi­tal­iza­tion and Health­care (IRCCS) in Italy, a team led the genet­ic analy­sis of 54 VARV sam­ples col­lect­ed from pre­vi­ous­ly pub­lished papers and research data­bas­es. I re-exam­ined the array.

These include four ancient VARV genomes from the Viking Age, two his­tor­i­cal VARV genomes from the 17th and 18th cen­turies, and 48 mod­ern VARV sequences pri­or to the 1980 erad­i­ca­tion of smallpox.