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The Forgotten History of Inoculation

Gavin Weightman—

The huge international effort to develop an effective vaccine against the coronavirus suggests that it is only with the development of modern medicine that an antidote could be found for a deadly virus. Yet the concept of immunization is hundreds, if not thousands, of years old. And its discovery had absolutely nothing to do with medical expertise: it was a folk procedure derived from common experience. 

Disease itself—smallpox—provided the clue to protecting against infection. It was a terrible affliction, which covered the victim’s body in burning pustules, killing and maiming. But smallpox had one redeeming feature: if you survived an attack you were sure to be immune for life. This suggested that if there was a way to get a mild attack, it would provide protection when the next epidemic struck without endangering your life. 

In China, dried scabs of smallpox pustules were sniffed like snuff to induce immunity. More commonly the infection was injected into the arm of a child or adult who was brave enough to try inoculation or “engrafting,” as it was known in Turkey and some other parts of the world.

In England, the medical profession knew about engrafting in the early 18th century as it had been described in papers sent to the Royal Society in London and published in its Philosophical Transactions. It had been observed mostly in Turkey where elderly Greek women equipped only with a rusty needle appeared to have great success immunizing children against smallpox. Their “vaccine” was the smallpox infection itself. This was collected from the pustules of the already infected and preserved in walnut shells. Engrafting involved nothing more than pricking the skin of the child, in the arm or leg or both, and rubbing in the infection. If smallpox “took,” as it invariably did, the patient developed symptoms of the disease that were mostly mild and after two weeks subsided. Reports suggested that it was a miraculous defense against smallpox but the medical profession found it abhorrent and quite incomprehensible. 

Their resistance was broken by a very brave aristocratic lady, Mary Wortley Montagu, who saw the Greek women in action when she lived briefly in Istanbul where her husband was ambassador. She had her son and later her daughter “engrafted” with complete success. Royalty was impressed, if the medical profession were mostly hostile. There followed in 1721 a bizarre piece of medical research the like of which would have been unthinkable today: prisoners in Newgate Gaol in London were offered freedom if they would undergo engrafting. All six volunteers survived. Next, some orphans were taken as guinea pigs, and they survived. 

Gradually, Royalty and the upper crust began to adopt engrafting, which became known as inoculation. It was for the elite only until a physician practicing in the Yorkshire woolen town of Halifax thought he would try it, having read the papers published in the Royal Society. Just as Lady Mary was a brave woman, the doctor, Thomas Nettleton, was a brave man. But he was driven to try inoculation by the terrible plight of families in Halifax and the small towns and villages that he served. If anyone doubted the efficacy of the procedure, he had stories to tell which still send a chill down the spine. He wrote it all down in a letter to a friend in London who passed it on to the Royal Society. 

His second patient, one of the first ever to be inoculated by a doctor in England, was a two years old girl. Four of the children in the family had already died of smallpox and were buried. Anxiously, he injected smallpox into her arm and observed the reaction. The girl was feverish, had a “convulsive fit,” and suffered the eruption of smallpox pustules on her body. But she survived. 

Nettleton recorded a great many heartrending stories of families desperate to save at least one of their children. However, he did so in the teeth of local opposition and decided to inoculate only those who approached him. It was a number of years before engrafting became acceptable, and it was made widespread and popular not by the leading doctors of the day but by rural surgeons.

Most medical histories have lost sight of this crucial era in the development of what became known as vaccination. I believe the reason is that when a country surgeon, Edward Jenner, proposed that it might be safer to inoculate with a milder disease known as cowpox that inoculation was forgotten about. 

Jenner dignified cowpox with a Latin invention: he called it variola vaccinae to mean “smallpox of the cow.” But nobody really knows what his vaccines were. In the late eighteenth century, medicine was blissfully ignorant of germs of any kind. That Jenner’s vaccine worked was, in retrospect, a miracle. However, it did not work quite as well as he had hoped; his vaccines needed a booster after a few years.

The virus which caused smallpox before it was killed off for good in the 1970s was one of a class of infections which affected a variety of animals. It was not, as Jenner thought, only an infection of cows but one of a family of orthopoxviruses. And it was a very long time before there was some understanding of why injecting smallpox or cowpox induced a mild does of the disease. I am not sure it is really understood now, though we do know it has to do with the way in which our immune system can be stimulated to set up defenses against an infection. 

Vaccination has been hugely successful saving millions of lives. But there is no telling if one will be found to protect against coronavirus. Whereas smallpox had been around for centuries, COVID-19 is new; we do not know if an attack triggers the body’s defenses in such a way that future attacks are easily repulsed. But it should be remembered that the very concept of inoculation goes far back into medical history and the pioneers, however rustic their techniques, should not be forgotten.


Gavin Weightman is a historian and former documentary filmmaker. He has written extensively on the history of science, and is the author of EurekaThe Frozen Water Trade, and The Industrial Revolutionaries.


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