In 1809, smallpox vaccination sounded too good to be true.

Could injection with a virus found in sick cows really prevent one of the most devastating diseases of the era?

A bold experiment during the United States’ first municipal vaccination campaign proved the answer was yes — and helped calm public doubt about vaccination.

People had good reason to be skeptical of the first vaccines: The practice was new, and everyone knew the stakes. Highly contagious, smallpox led to fevers and skin rashes that could leave permanent scars. In 3 of 10 cases, the disease was fatal.

In 1796, English physician Edward Jenner developed the first vaccine using the cowpox virus, which could be spread from infected cows to humans and which resulted in a smallpox-like rash. But a doubting public wondered whether Jenner’s vaccine could really protect humans from smallpox.

In 1809, officials in Milton, Mass., decided to test its efficacy with the help of 12 children who had received the vaccine during the town’s free municipal vaccination campaign, the first of its kind in the United States, a few months earlier.

Amos Holbrook, a local doctor who believed in the vaccine, injected the vaccinated children with a small amount of live smallpox virus. Then, the children were quarantined together and carefully observed for any sign of smallpox.

Fifteen days later, the quarantine ended. Not a single child had contracted smallpox.

Milton residents were thrilled. It was “additional proof of the never failing power of that mild preventive the Cow pock, against Small pox infection,” wrote an official on a card certifying the event. The handwritten card, which lists the children’s names, is now held by the Smithsonian Institution’s National Museum of American History.

The demonstration was a landmark for public acceptance of vaccination. News of the test was distributed to every town in Massachusetts, and it helped create momentum for an 1810 law that directed every municipality in the state to offer vaccination.

Soon, smallpox vaccination became routine, and the practice spread over the world. By 1980, smallpox had been eradicated — thanks in part to 12 young smallpox vaccine pioneers.