The beginning of smallpox inoculation in the Americas is often linked back to the knowledge of Onesimus, an enslaved African man. He was "purchased" as a "slave" for Cotton Mather, a Puritan church minister in Boston. Mather records how Onesimus revealed to him a method of smallpox inoculation that he had undergone while still in Africa.

In 1721, Mather steals this knowledge to promote mass inoculation against smallpox after an outbreak of the disease kills around 14% of the population in Boston. Inoculation immediately became controversial, with some Bostonians claiming that it is more dangerous than smallpox itself.