Beware the vaccine. 19th century illustration showing the mistrust of the French public for the smallpox vaccine. The British physician Edward Jenner (1749-1823) performed the first vaccination in 1796 when he used fluid from a cowpox blister to inoculate a boy against the more dangerous smallpox. Smallpox is an often-fatal disease caused by the Variola virus. Prior to vaccination it killed millions of people each year.