In April of 1721, a smallpox epidemic hit Boston, infecting 5,889 residents and killing 844. October alone claimed 411 lives in a city of 13,000. The disease was responsible for three-quarters of all Boston deaths from all causes in that year.
To those affected, which would have been most everyone, the routine ravages of smallpox were bad weather—as destructive and inevitable as a hurricane or blizzard. The Reverend Cotton Mather was not satisfied, however. A slave had described to the Reverend his own inoculation against the disease in Africa, of which Mather wrote, "he told me that he had undergone the operation which had given something of the smallpox and would forever preserve him from it, adding that was often used in West Africa.'' Mather confirmed the account with several other West African slaves.
The procedure involving the transfer of pus from a smallpox sore to a small wound made in the skin of the recipient of the inoculation. The resulting infection would be relatively mild, but the inoculated would wind up with immunity all the same.
By 1721, this was an old practice, globally speaking—inoculation had for centuries been common folk medicine. Around 1,000 AD, it had caught on in India and China in a somewhat different form in which the dried crusts from smallpox sources were ground up and either inhaled or rubbed into a scratch in the skin. In the 15th century, a similar practice had been adopted across the Middle East in which the dried crusts were delivered via a sharp pin. In 1717, Lady Mary Mortley Montagu, the wife of the British Ambassador to Turkey, had her son inoculated against smallpox and would later attempt to bring the practice to England, with moderate success.
On June 26, 1721, Mather convinced a doctor named Zabdiel Boylston to inoculate his own son and two slaves. All three became mildly ill but soon recovered. Following from the experiment's apparent success, Mather went on to make a public case for inoculation, setting off a bitter debate about the practice's safety. Through the ensuing controversy, William Douglass, Boston's only university-trained doctor, would represent the anti-vax position, which was widely held among the public as well.
Douglass' concerns were obvious enough. While the public at large was more likely to be concerned about god's will and divine law, Douglass made sensible points, particularly relating to how Boylston and Mather went about their ensuing inoculation experiments. How can we be sure the inoculation won't cause a fatal case of smallpox in the inoculated? Could the disease spread from the inoculated to others? Could the infection, however mild, increase one's susceptibility to other diseases? Ultimately, Douglass was less anti-inoculation than he was pro-caution, calling Boylston and Mather's inoculations a "rash and thoughtless Procedure." Douglass felt, for example, that the inoculated should be quarantined for a period following the inoculation.
Many others, however, were very much so anti-vax on principle, and for much less scientific reasons. Interfering with the disease in such a fashion could be seen as an affront to god himself, who had surely created smallpox with divine intent. One pamphleteer, in making this argument, cited the biblical passage: "I kill and I make alive; I wound and I heal." If smallpox is evil, then it is an evil allowed by god and is according to god's will. "There is no rule in the Word of God to found inoculation on, therefore inoculation cannot be according to the Will of God."
Inoculation is thus, "violence unto the Law of Nature."
Finally, in November of 1721, things came to a head and a bomb was pitched through the window of the Reverend Cotton Mather. It failed to explode, but contained the note, "Cotton Mather, you dog, dam you! I'll inoculate you with this; with a pox to you.''
Mather and Boylston wound up with surprisingly thorough data from their inoculation program. Of 287 patients inoculated, only 2 percent died, compared to the 15 percent mortality rate of the naturally occurring disease. Their work wound up being one of the first clinical trials in history and their use of experimental and control groups would prompt the adoption of the practice in future work.
The bigger picture:
Mather and Boylston came out of their project looking pretty good, but Douglass had a point. "Given that Mather was neither carrying out his inoculations in an organized manner nor isolating newly inoculated patients appropriately, Douglass's criticism was legitimate," notes an entry in Harvard's Contagion: Historical Views of Diseases and Epidemics. "Inoculation could indeed cause fatal cases of smallpox, and because inoculation proceeded by the direct transmission of bodily matter from one person to another through an open cut, diseases like syphilis could be spread by the procedure as well."
Douglass, as the OG anti-vaxxer, was onto something, but the scenario in 1721 was nearly the opposite from the one in which we now find ourselves. If anything, the saliency of his position nearly 300 years ago highlights holes in the arguments of contemporary anti-vaxxers.
Through the 1921 epidemic, Mather and Boylston were delivering inoculations based on folklore and intuition rather than science and with a dangerous underabundance of caution. Now, common vaccinations are supported by libraries of research and evidence and are delivered in a rigorous and tightly regulated manner. The all-natural (all-god) angle seems to have remained more or less constant, at least.