The History of Vaccination: From Ottoman Variolation to Jenner's Cowpox

Smallpox Killed 300 Million People in the 20th Century Alone — Until a Milkmaid's Observation Changed Everything

Smallpox killed approximately 300 million people during the 20th century — more than both World Wars combined. It had been one of humanity's most lethal infectious diseases for at least 3,000 years, with evidence of smallpox lesions found on Egyptian mummies including Ramesses V, who died in 1157 BCE. The World Health Organization declared smallpox eradicated on May 8, 1980, making it the first (and still only) human disease eliminated from the planet by deliberate vaccination campaigns. That eradication traces its origins not to a laboratory but to a series of folk observations made across the Ottoman Empire, China, West Africa, and the English countryside — all arriving at the same counterintuitive insight: that controlled exposure to disease could prevent worse disease.

The history of vaccination is simultaneously a history of scientific discovery, of class and gender (it was women, including a socialite and milkmaids, who provided crucial observations), and of the political resistance that has accompanied every new vaccine from smallpox to COVID-19.

Variolation: The Ottoman Practice That Preceded Jenner by a Century

The practice of variolation — deliberately infecting a healthy person with material from a mild smallpox case to induce immunity — was practiced in China, India, and the Ottoman Empire well before it reached Western Europe. Chinese practitioners in the 10th century used dried and powdered smallpox scabs blown into the nostrils. Ottoman practitioners used a different technique: inserting pus from smallpox pustules under the skin using a needle, a practice described by Lady Mary Wortley Montagu, wife of the British Ambassador to Constantinople, in letters from 1717.

Lady Mary Wortley Montagu had survived a severe case of smallpox herself in 1715, which had left her face scarred and cost her her eyelashes. When she witnessed the Ottoman practice and saw that it appeared safe and effective, she arranged for her own five-year-old son to be variolated in 1718 — the first Briton to undergo the procedure. She brought the practice to England, campaigned for it among the aristocracy and medical establishment, and organized a demonstration on prisoners at Newgate Prison in 1721 to prove its safety.

Onesimus and Cotton Mather: The American Discovery

Simultaneously with Lady Montagu's efforts in England, a different transmission route brought variolation knowledge to Boston. Cotton Mather, the Puritan minister, learned of the practice from Onesimus, an enslaved African man in his household, who described the technique and showed Mather a scar from his own childhood inoculation in Africa. Onesimus told Mather that smallpox inoculation was practiced in his homeland and that "people take Juice of Small-Pox; and Cutty-skin, and Putt in a Drop."

When a smallpox epidemic hit Boston in 1721 — the same year as the Newgate demonstrations in England — Mather persuaded physician Zabdiel Boylston to inoculate approximately 240 people. The results were striking: inoculated individuals died at a rate of roughly 2%, while uninoculated smallpox cases in the epidemic died at rates of 14–17%. The medical establishment (represented by the physician William Douglass) opposed the practice vehemently; someone threw a bomb into Mather's house with a note: "Cotton Mather, You Dog, Dam You; I'll inoculate you with this, with a Pox to you." Anti-vaccination sentiment is not a modern invention.

Edward Jenner and the Cowpox Experiment of 1796

Edward Jenner was a Gloucestershire country physician who had heard the local folk belief that milkmaids who contracted cowpox (a mild disease acquired from cattle) were thereafter immune to smallpox. This belief was widespread enough to be documented independently in several English counties. Jenner spent nearly two decades investigating it before conducting his famous experiment.

On May 14, 1796, Jenner took pus from cowpox blisters on the hands of milkmaid Sarah Nelmes and inoculated eight-year-old James Phipps — the son of Jenner's gardener — in both arms. Phipps developed a mild fever and local reaction, then recovered. On July 1, Jenner variolated Phipps with material from a smallpox case. Phipps did not develop smallpox. Jenner repeated the cowpox exposure and smallpox challenge several times over the following months with the same result.

• Jenner submitted his findings to the Royal Society, which declined to publish them without more data
• He published privately in 1798: An Inquiry into the Causes and Effects of the Variolae Vaccinae
• The word "vaccine" derives from vacca, Latin for cow
• The Royal Jennerian Society was founded in 1803 to promote vaccination; by 1807 the British National Vaccine Establishment was distributing vaccine to the poor without charge
• Napoleon, at war with Britain, nonetheless had his entire army vaccinated and released British prisoners of war who were physicians studying vaccination

What Made Vaccination Better Than Variolation

Jenner's cowpox-based vaccine had a crucial advantage over variolation: it did not use smallpox virus itself. Variolated individuals, though usually developing only mild disease, were genuinely infected with smallpox and could transmit it to unvaccinated contacts. Variolation killed approximately 2% of recipients — dramatically better than epidemic smallpox mortality, but still a real risk. Jenner's vaccine induced immunity through a related but distinct virus (vaccinia, closely related to cowpox) that was not transmissible as smallpox and did not cause serious disease in healthy individuals. This made mass vaccination campaigns logistically feasible and ethically defensible in ways that mass variolation was not.

The global eradication campaign, organized by WHO under the leadership of D.A. Henderson beginning in 1967, achieved the last naturally occurring smallpox case on October 26, 1977 (Ali Maow Maalin, in Somalia). The final human-transmitted cases occurred in 1978 when a medical photographer at Birmingham University was infected by accidental laboratory release. The course from an enslaved man's scar shown to a Puritan minister and an Ottoman practice described in letters by a scarred socialite, to the elimination of a disease that had killed hundreds of millions, took approximately 260 years.