On April 22, 1721, the HMS Seahorse arrived in Boston from the West Indies, carrying goods, cargo, and, unbeknownst to its crew, a deadly virus. Soon, a smallpox epidemic had broken out in Boston, causing death and panic across the city. The clergy, including the famed Cotton Mather, relied on fasting and prayer to fight the disease. But a new theory was also being offered by the scientific world: inoculation. The fierce debate over the right way to combat the tragedy would become a fierce battle between faith and reason that set the city aflame with rage and riot.