Smallpox

Smallpox was one of the most consequential infectious diseases in human history. Caused by the Variola virus, it killed an estimated 300 to 500 million people in the 20th century alone, more than both world wars combined. Cumulative mortality across all of human history is likely over one billion.

The disease is ancient — evidence of smallpox-like pustules appears on the mummified remains of Pharaoh Ramesses V (died 1145 BCE), and the Antonine Plague of 165–180 CE is widely attributed to smallpox. Variola became endemic across Eurasia and Africa in historical times and was carried to the Americas by European contact in the 16th century, where it killed an estimated 90% of some Indigenous populations and played a central role in the demographic collapse that facilitated European colonisation.

Smallpox is the only human infectious disease to have been eradicated. Edward Jenner's 1796 demonstration of vaccination using cowpox (vaccinia) provided the basis for protection. The WHO's Intensified Smallpox Eradication Programme, launched in 1966, achieved its goal in 1980. The last naturally-acquired case occurred in Somalia in October 1977. Two known stocks of the virus remain, at the CDC in Atlanta and the Vector Institute in Russia.