....TO EARLY New Englanders, smallpox was one of life’s many imponderables. No one really knew where the disease came from. Was it carried by bad air, or sent as a form of divine retribution for personal failings? Boston had plenty to fear on both counts—one observer described the town at low tide as “a very stinking puddle.” Medical knowledge was still primitive; a learned scientist, John Winthrop Jr., kept what he thought was a unicorn horn in his cabinet. For most, the first line of defense was the prayer book....This time, however, the city was better prepared, thanks to several unlikely heroes. Cotton Mather is not always the easiest figure to admire. The scion of a dynasty of ministers, he fought a lengthy rear-guard action against time, trying to stanch the ebbing of power among the city’s religious authorities. But he was surprisingly modern in some ways, and paid attention to the new forms of knowledge coming in on those ships. Another contradiction lay in his racial attitudes—his writings suggest that, more than most of his contemporaries, he admired Africans, but he also accepted slavery, and had raised no objections when his congregation presented him with a young slave in 1706. He named him Onesimus, after a slave belonging to St. Paul.

Mather had come close to choosing a career in medicine, and devoured the scientific publications of the Royal Society in London. As the society began to turn its attention to inoculation practices around the world, Mather realized that he had an extraordinary expert living in his household. Onesimus was a “pretty Intelligent Fellow,” it had become clear to him. When asked if he’d ever had smallpox, Onesimus answered “Yes and No,” explaining that he had been inoculated with a small amount of smallpox, which had left him immune to the disease. Fascinated, Mather asked for details, which Onesimus provided, and showed him his scar. We can almost hear Onesimus speaking in Mather’s accounts, for Mather took the unusual step of writing out his words with the African accent included—the key phrase was, “People take Juice of Small-Pox; and Cutty-skin, and Putt in a Drop.”

Excited, he investigated among other Africans in Boston and realized that it was a widespread practice; indeed, a slave could be expected to fetch a higher price with a scar on his arm, indicating that he was immune. Mather sent the Royal Society his own reports from the wilds of America, eager to prove the relevance of Boston (and by extension, Cotton Mather) to the global crusade against infectious disease. His interviews with Onesimus were crucial. In 1716, writing to an English friend, he promised that he would be ready to promote inoculation if smallpox ever visited the city again.

When it did, Mather pursued a determined course of action, asking doctors to inoculate their patients and ministers to support the plan. His call was answered by only one person, an apothecary named Zabdiel Boylston, who began by inoculating his 6-year-old son, Thomas, and two slaves......