The news was terrifying to colonists in Massachusetts: Smallpox had made it to Boston and was spreading rapidly. The first victims, passengers on a ship from the Caribbean, were shut up in a house identified only by a red flag that read “God have mercy on this house.” Meanwhile, hundreds of residents of the bustling colonial town had started to flee for their lives, terrified of what might happen if they exposed themselves to the frequently deadly disease. 

They had reason to fear. The virus was extremely contagious, spreading like wildfire in large epidemics. Smallpox patients experienced fever, fatigue and a crusty rash that could leave disfiguring scars. In up to 30 percent of cases, it killed.

But the smallpox epidemic of 1721 was different than any that came before it. As sickness swept through the city, killing hundreds in a time before modern medical treatment or a robust understanding of infectious disease, an enslaved man known only as Onesimus suggested a potential way to keep people from getting sick. Intrigued by Onesimus’ idea, a brave doctor and an outspoken minister undertook a bold experiment to try to stop smallpox in its tracks.