On 14 May 1796 a country doctor in Gloucestershire took some fluid from a sore on the hand of a milkmaid named Sarah Nelmes, who had caught cowpox from a cow called Blossom. He made two small cuts in the arm of an eight year old boy, James Phipps, the son of his gardener, and rubbed the fluid in.
The boy developed a mild fever and a sore at the site, and recovered within a fortnight. On 1 July, Edward Jenner deliberately inoculated him with matter taken from a fresh smallpox pustule. Nothing happened. He repeated the challenge some months later, and again nothing happened.
It is an experiment that no ethics committee would now approve, performed on a child who could not consent, to test a hypothesis its author could not explain. It also ended the disease that had been killing around four hundred thousand Europeans a year.
What Smallpox Was
It is difficult now to convey how thoroughly smallpox saturated ordinary life. It killed roughly three in ten of the people it infected and scarred most of the survivors. It was responsible for around a third of all cases of blindness in Europe. It killed five reigning European monarchs in the eighteenth century. In Britain it was so nearly universal in childhood that advertisements for missing persons routinely described faces as pockmarked, because an unmarked face was worth mentioning.
The virus had no animal reservoir, spread only between humans, and produced a visible rash in every case. Those three facts, which nobody appreciated at the time, are why it was later possible to hunt it to extinction.
The Practice That Came Before
Jenner did not invent the idea of giving somebody a disease on purpose. Variolation, deliberate infection with smallpox itself using material from a mild case, had been practised for centuries in China, India, Africa and the Ottoman Empire.
It reached Britain through two routes at almost the same moment. Lady Mary Wortley Montagu, wife of the ambassador in Constantinople and herself disfigured by the disease, had her son inoculated there in 1718 and campaigned for the practice at home. In Boston in 1721, Cotton Mather learned the method from an enslaved West African man named Onesimus, who described it as routine where he had grown up, and persuaded a doctor to try it during an epidemic.
Variolation worked. It produced a genuine, usually milder infection and lifelong immunity, and cut the death rate from around 30 percent to perhaps 2 percent. But 2 percent is not zero, the inoculated person was contagious and could start an outbreak, and the procedure as sold by British practitioners often involved weeks of preparatory bleeding and purging at considerable expense.
The Dairy Observation
The folk belief that milkmaids did not catch smallpox was common in dairy country, and Jenner was not the first to act on it. A Dorset farmer named Benjamin Jesty inoculated his wife and two sons with cowpox in 1774 during an outbreak, using a darning needle and material from a neighbour’s cow. They never caught smallpox. He published nothing and was mocked locally for it.
What Jenner did that Jesty did not was treat the belief as a claim to be tested and then argue it into the medical literature. He collected case histories going back decades, noticed that people who had had cowpox often resisted variolation entirely, and worked out that not every pustule on a cow conferred protection, which is why the folk rule sometimes appeared to fail.
After the Phipps experiment he tried to publish through the Royal Society, which declined it and advised him not to risk his reputation. He carried out further cases, including his own eleven month old son, and in 1798 published at his own expense a seventy five page book usually shortened to the Inquiry. He called the material variolae vaccinae, smallpox of the cow, from the Latin vacca. The word vaccine comes from that sentence.
Adoption, and the Objections
It spread with remarkable speed for the period. Within three years the practice had reached most of Europe, and by 1800 material had been sent to the United States and India. In 1803 a Spanish expedition carried it to the Americas and the Philippines by taking twenty two orphan boys aboard ship and vaccinating them in sequence, arm to arm, so that a live chain of infection survived the crossing. Napoleon had his army vaccinated and released two English prisoners at Jenner’s request, remarking that he could refuse that man nothing.
The objections were not stupid either, and they came in several kinds.
- Practical. Arm to arm transfer moved other diseases along with the vaccine, syphilis included, until animal derived lymph replaced it
- Commercial. Variolation was a profitable business, and the men who sold it fought the new method
- Religious. Introducing animal matter into a human body was argued to be unnatural. James Gillray’s famous cartoon of 1802 shows vaccinated patients sprouting cows from their limbs
- Political. The British Compulsory Vaccination Acts of 1853 and 1867 made refusal punishable by fines and imprisonment, and produced the Anti Vaccination League and, in 1885, a march of a hundred thousand people through Leicester. The conscientious objection clause added in 1898 is the origin of that phrase in English law
Jenner himself did not profit. He gave the method away, ran free vaccination clinics in a hut in his garden, and was eventually voted grants by Parliament to compensate for the practice he had lost while promoting it.
Nobody Knew Why It Worked
This is the part worth holding on to. In 1796 there was no germ theory, no virology, and no concept of an immune system. Nobody had seen a virus, and nobody would until the electron microscope in the 1930s. Jenner’s explanation involved a substance he thought originated in a horse disease called grease, transferred to cows by farm workers.
The mechanism only became discussable eighty years later, when Pasteur established that specific organisms cause specific diseases. Working on chicken cholera in 1879, Pasteur found that an old, weakened culture protected birds against a fresh one, and generalised the principle into attenuation. He named the whole class of preparations vaccines, explicitly in Jenner’s honour, for a procedure that had nothing to do with cows.
The same gap between a working treatment and an explanation of it appears throughout medicine. Penicillin was used on patients before anyone could say what it did to a bacterial cell wall, and John Snow stopped a cholera outbreak thirty years before the organism responsible was identified.
Eradication
The World Health Organization launched an intensified eradication campaign in 1967, when smallpox was still endemic in 31 countries and killing about two million people a year. The strategy that finished it was not mass vaccination but surveillance and containment: find each case, vaccinate everyone around it, and let the chain of transmission die.
The last natural case of the severe form was a three year old girl in Bangladesh in 1975. The last natural case of any form was Ali Maow Maalin, a hospital cook in Somalia, in October 1977. He recovered, and spent much of his later life working on polio vaccination campaigns in the same region.
There was one further death. In 1978 a medical photographer named Janet Parker contracted smallpox at the University of Birmingham, where the virus was held in a laboratory below her darkroom, and died. The head of that laboratory took his own life during the investigation.
The World Health Assembly declared the disease eradicated on 8 May 1980. It remains the only human infectious disease ever eliminated, and the stocks that survive sit in two freezers, one in Atlanta and one in Russia.
The Cow That Was Not a Cow
A final oddity. When the virus used in modern smallpox vaccines was sequenced, it turned out not to be cowpox. It is vaccinia, a distinct species whose closest known relative is horsepox, which fits Jenner’s own belief about the horse disease better than the story everyone tells about milkmaids.
Where vaccinia came from is still unresolved, since the strains passed from arm to arm and animal to animal for a century and a half before anyone thought to characterise them. The most successful medical intervention in history was carried out for two hundred years with a virus nobody had correctly identified, against a disease nobody could see, on a principle nobody could explain, and it worked every time.
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