Evidence of smallpox has been present since the dawn of human civilization, and is estimated to be at least 10,000 years old.
However, it wasn't introduced to Europe until sometime between the fifth and seventh centuries. Frequent outbreaks left nearly 400,000 dead a year.
European colonizers, particularly the Spanish and Portuguese, spread smallpox to the Indigenous peoples of the Americas. This is thought to be, in some cases, an early use of biological warfare. With no immunity to the virus, smallpox devastated the native populations.
Lady Mary Wortley Montague, after suffering smallpox herself, had her children varioliated while living in the Ottoman Empire, so that they would contract a milder case of smallpox
Innoculation for smallpox was used in China, India, and Africa before it was introduced to the west.
When word of Lady Montague's successes came to Europe, the practice of variolation became a 50 year movement to prevent smallpox. However, the immunity to smallpox that innoculating provided was temporary.
In 1757, an 8 year old Edward Jenner was inoculated in Gloucestershire.
A common belief in the 18th century was that dairymaids were immune to smallpox. After hearing a dairymaid confirm this, he began to experiment with a more permanent alternative to variolation.
“I shall never have smallpox for I have had cowpox.