In the late 18th century, Edward Jenner investigated the relationship between cowpox and immunity to smallpox. His 1796 inoculation experiment became a famous event in the history of vaccines.
People had already practiced variolation before his work. The spread of cowpox vaccination later provided an important foundation for smallpox control and modern immunization.
Invention of the vaccine
Inoculation was already a standard practice in Asian and African medicine, but involved serious risks, including the possibility that those inoculated would become contagious and spread the disease to others. In 1721, Lady Mary Wortley Montagu had imported variolation to Britain after having observed it in Constantinople. While Johnnie Notions had great success with his self-devised inoculation (and was reputed not to have lost a single patient), his method's practice was limited to the Shetland Islands. Robert Sutton's method had similar success in Suffolk. Voltaire wrote that at this time, 60% of the population caught smallpox and 20% of the population died from it. He also stated that the Circassians used the inoculation from time immemorial, and that the Turks may have borrowed the custom from them. In 1766, Daniel Bernoulli analyzed smallpox morbidity and mortality data to demonstrate the efficacy of inoculation.
By 1768, the English physician John Fewster had realised that prior infection with cowpox rendered a person immune to smallpox. In the years following 1770, at least five investigators in England and Germany (Sevel, Jensen, Jesty 1774, Rendell, Plett 1791) successfully tested a cowpox vaccine against smallpox in humans. For example, the Dorset farmer Benjamin Jesty successfully vaccinated with cowpox and presumably induced immunity in his wife and two children during the 1774 smallpox epidemic, though it was not until Jenner's work that the procedure became widely understood. Jenner may have been aware of Jesty's procedures and success. In 1780, Jacques Antoine Rabaut-Pommier made similar observations in France.
Jenner postulated that the pus in blisters from sufferers of cowpox (a disease similar to smallpox but much less virulent) protected them from smallpox. On 14 May 1796, he tested his hypothesis by inoculating James Phipps, the eight-year-old son of Jenner's gardener. Jenner scraped pus from cowpox blisters on the hands of Sarah Nelmes, a milkmaid who had caught cowpox from a cow called Blossom (whose hide now hangs on the wall of the St George's Medical School library, now in Tooting, London). Phipps was the 17th case described in Jenner's first paper on vaccination.
Jenner inoculated Phipps through two small cuts on his arm that day; this led to a fever and some uneasiness, but no full-blown infection. On 1 July 1796, Jenner injected Phipps with variolous material, the routine method of immunisation at that time, and again no disease followed. Phipps was later challenged with variolous material and again showed no sign of infection. There were no unexpected side effects, and neither Phipps nor any other recipients underwent any future 'breakthrough' cases.
Jenner's biographer, John Baron, later speculated that it was Jenner's observation of the unblemished complexion of milkmaids that led to his understanding that it was possible to be inoculated against smallpox by being exposed to cowpox, that is, he did not build on the work of his predecessors. The milkmaid story is still widely repeated even though it appears to be a myth.
Jenner continued his research and reported it to the Royal Society, though the initial paper was not published. After revisions and further investigations, he published his findings on the 23 cases, including his 11-month-old son Robert. Some of Jenner's conclusions were correct, some erroneous; modern microbiological and microscopic methods would make his studies easier to reproduce. The medical establishment deliberated at length over his findings before accepting them. Eventually, vaccination was accepted, and in 1840, the British government banned variolation – the use of smallpox to induce immunity – and provided vaccination using cowpox free of charge .