The first vaccine was developed in 1796 by Edward Jenner, an English physician who deliberately infected an eight-year-old boy with cowpox to protect him from smallpox. The idea was radical but rooted in a simple observation: milkmaids who caught cowpox, a mild disease from cattle, seemed to never get smallpox. Jenner tested that folk wisdom with a now-famous experiment that would eventually lead to the complete eradication of one of humanity’s deadliest diseases.
Smallpox Before the Vaccine
To understand why Jenner’s experiment mattered, you need to understand how terrifying smallpox was. The disease killed between one in seven and one in four of everyone it infected. In 18th-century London, smallpox was likely the single most lethal cause of death, responsible for 6 to 10 percent of all burials. It hit children hardest. In Kilmarnock, Scotland, 94 percent of smallpox victims between 1728 and 1763 were under seven years old. In Manchester, out of 589 smallpox deaths recorded between 1769 and 1774, only one was an adult over age 10.
People weren’t helpless, though. Long before Jenner, cultures across Asia, Africa, and the Ottoman Empire practiced something called variolation: intentionally exposing a healthy person to a small amount of smallpox material to trigger a mild infection and lifelong immunity. In China and parts of Africa, dried smallpox scabs were blown into the nose. In Europe, the material was inserted through a cut in the skin. The practice reached England in 1717, when Lady Mary Wortley Montagu, wife of the British ambassador to Constantinople, observed it in the Ottoman Empire and brought it home. Around the same time, Cotton Mather learned about variolation from his enslaved servant, Onesimus, and promoted it during a 1721 smallpox epidemic in Boston.
Variolation worked, but it was a gamble. Between 1 and 2 percent of those who underwent the procedure died from it, compared to the 15 to 25 percent who died from naturally caught smallpox. Those odds were better, but far from safe. Worse, the mild infection variolation caused was still contagious and could spark new outbreaks. Even royalty wasn’t spared: King George III lost a son to the procedure.
Jenner’s Key Observation
Jenner was a country doctor in Gloucestershire, an area full of dairy farms. He noticed that milkmaids who had been infected with cowpox, a relatively harmless disease that caused blisters on the hands, appeared immune to smallpox. This wasn’t a new observation among rural communities, but Jenner was the first to pursue it scientifically. He wasn’t even the first to act on it. In 1774, a farmer named Benjamin Jesty in Dorset used cowpox material to inoculate his wife and two sons. Two of his subjects were later deliberately exposed to smallpox through variolation and showed no signs of infection. But Jesty was a farmer, not a physician, and he never published his results or pursued the idea further.
What set Jenner apart was his decision to document, test, and publicize the method in a way the medical establishment could evaluate.
The 1796 Experiment
In May 1796, Jenner found a young dairymaid named Sarah Nelmes who had fresh cowpox blisters on her hands and arms. He took material from one of her lesions and scratched it into the skin of James Phipps, an eight-year-old boy. Phipps developed a mild cowpox infection and recovered quickly. Then came the crucial test: Jenner later exposed the boy to actual smallpox material through variolation. Phipps showed no symptoms. The cowpox had made him immune.
The reason this worked comes down to biology. Cowpox and smallpox are closely related viruses in the same family. When the immune system fights off cowpox, it produces antibodies that target proteins on the virus’s outer surface. Those same proteins appear on the smallpox virus, so the antibodies recognize and neutralize it too. The body essentially learns to fight smallpox by practicing on a much less dangerous relative.
Resistance and Recognition
Jenner’s findings were not immediately embraced. He submitted his results to the Royal Society, which declined to publish them. Undeterred, he conducted additional experiments and in 1798 self-published a treatise laying out his evidence. He followed it with another publication in 1801, titled “On the Origin of the Vaccine Inoculation.” The word “vaccine” itself comes from the Latin word “vacca,” meaning cow, a direct reference to the cowpox material at the heart of his method.
Over time, the evidence became too strong to ignore. Vaccination was safer than variolation, didn’t carry the risk of spreading full-blown smallpox, and reliably prevented the disease. Acceptance grew, and within just a few years the vaccine was being distributed across continents.
Spreading the Vaccine Worldwide
Getting a live biological material across the world in an era before refrigeration was a serious logistical challenge. For short distances or cool climates, the cowpox material could be dried on ivory points or lancets, pressed between small glass plates, or soaked into threads and dried. Using these methods, the vaccine reached Britain, North America, southern and central Europe, and the Mediterranean basin by 1800, and Scandinavia and Russia by 1801.
Longer distances in warmer climates required a different approach. The vaccine was kept alive through arm-to-arm transfer: one person would be vaccinated, and a week later, material from their resulting blister would be used to vaccinate the next person. This chain of living vaccine could travel thousands of miles. The British military used this method to vaccinate troops across India. In 1803, a Spanish expedition led by Francisco Balmis sailed for Central and South America, carrying the vaccine through a relay of children who were vaccinated in sequence throughout the voyage.
From One Experiment to Eradication
Jenner’s method laid the foundation for a global campaign that took nearly two centuries to complete. Vaccination programs expanded over the 1800s and 1900s, and in 1967 the World Health Organization launched an intensified effort to eradicate smallpox entirely. The last naturally occurring case was recorded in 1977. On May 8, 1980, the WHO officially declared smallpox eradicated, making it the first and still the only human disease eliminated through vaccination.
The entire concept of vaccination, now used against dozens of diseases, traces back to a country doctor, a dairymaid’s blistered hands, and an eight-year-old boy in rural England.