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In focus

Smallpox in the archives

by Anita Guerrini

Eighteenth-century Europeans took part in the largest human experiment ever conducted: inoculation against smallpox. Anita Guerrini reveals the central role of the Philosophical Transactions in circulating information about the technique and the complex ethical issues around the practice.

Through the Royal Society archives we can retrace how smallpox epidemics in the 1720s on both sides of the Atlantic brought new attention to the technique also known as variolation, which had long been known elsewhere in the world. For instance, the Turkish practice involved choosing someone – preferably “some Boy, or young Lad, of a sound healthy temperament” – with a mild case of smallpox, but one with distinct “pocks” or pustules. The inoculator pricked one or more of the pocks with a needle, collecting the “matter” within. This matter was then inserted into several deep scratches (sufficient to draw blood), most often in the arm of the person being inoculated. In theory, within a week the inoculated person would come down with a mild case of smallpox and recover a few days after that, with minimal scarring from the pocks. It was widely believed that smallpox struck only once in a lifetime, so inoculation would therefore provide lifelong immunity against a dreaded disease.

The Italian physician Emanuele Timone, a Fellow of the Royal Society resident in Constantinople, described this technique in a letter sent to the Society in 1714.

Timone, who became the physician to the new British Ambassador to the Sublime Porte soon after the publication of the letter in the Philosophical Transactions, may have been hired by Edward Wortley Montagu and his wife, Lady Mary Wortley Montagu specifically because of his expertise in inoculation. Lady Wortley Montagu later persuaded the embassy’s surgeon, Charles Maitland, to inoculate her young son in 1718. Timone’s article cited two unsuccessful cases, but he maintained that these patients died of pre-existing conditions, not as a result of the inoculation.

This practice, with variations, was in fact well-known in the middle and far East and in parts of Africa. The Chinese practice, which involved inhaling dried smallpox scabs, had been mentioned at a meeting of the Society a decade earlier, on 14 February 1700, by Dr Clopton Havers

Many enslaved persons in North America, including Onesimus, a servant of the New England minister Cotton Mather, knew about it. Mather reported on the practice to the Society in the letter below, and became an enthusiastic supporter of inoculation during the Boston epidemic in 1721.

Letter, from Cotton Mather to James Jurin

Creator: Cotton Mather Reference number: CLP/23ii/31

A human trial on six prisoners from Newgate Prison in London, supervised by Hans Sloane, proved to be successful in that none of the prisoners died and they appeared to be immune to smallpox. Nonetheless, no one understood how inoculation worked, or why it sometimes failed dismally. This widespread human experiment continued for nearly a century before it was superseded by Edward Jenner’s cowpox-based vaccine which, itself, was tested in conditions that maybe today would be considered unethical.

Smallpox lesion on a child's arm.
Edward Jenner, An inquiry into the causes and effects of the variolae vaccinae, 1798.

The sunny account in the 1714 Philosophical Transactions obscured how little actually was known about smallpox or about inoculation. A longer Latin section appended to this account explained the practice in terms of current medical theory but did not make things any clearer.

In 1721, the physician James Jurin, a supporter of inoculation, became secretary of the Royal Society. He placed an advertisement in the Philosophical Transactions, soliciting letters from readers that recounted their experiences of inoculation, and over the next several years he received dozens of accounts, mainly from physicians and surgeons but also from laymen. Employing these cases to calculate the odds of survival from inoculation as opposed to natural smallpox, he concluded in a series of pamphlets that the odds of dying from inoculation-induced smallpox were about one in 50, while the odds for naturally-induced smallpox were one in 8, or even, in epidemic years, one in 6. However, the letters themselves, which are in the Royal Society archives along with lists of inoculations performed by Charles Maitland (who had inoculated the Newgate prisoners) and the Royal Surgeon Claude Amyand, tell stories that Jurin’s extraction of numbers could not reveal.

Jurin's great smallpox experiment

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The wave of optimism that Jurin’s numerical proofs provided, as well as the successful Newgate trials, led to a flood of inoculations. The Royal Family and the nobility led the way, urged on by Lady Mary Wortley Montagu. Many others followed their lead, conscious of the risk but more fearful of the disease. It was distressingly widespread. Silvanus Bevan, probably a surgeon in Hertfordshire, sent Jurin “An Account of the number of families and people in Ware affected by small pox in 1722.” 

Of a total of 2500 people, 1600 had already had smallpox, and over 600 contracted it in the current outbreak. Of these, 72 died, a mortality rate of about one in 8. Only 300 had never contracted the disease.

The surgeon William Cheselden described “The Cases of Master and Miss Eyles” in 1725. Cheselden disavowed responsibility, noting that “They were both inoculated by their own Choice being perswaded from common report that there was little or no danger in it.” 

Paper, 'Case of Master and Miss Eyles' by Mr [William] Cheselden

Creator: William Cheselden Reference number: CLP/23i/41

However, the outcome was not as planned. Miss Eyles duly broke out in “Eruptions” eleven days after the inoculation, and then suddenly died. Master Eyles’s eruptions appeared a few days later, following on a number of other symptoms that included “a shooting pain in his Head.” Because of, or more likely despite, the usual treatment of bleeding and blistering, Eyles recovered, somewhat to Cheselden’s surprise. 

A large number of trials were conducted on children. Elizabeth and Joseph Brooksbank’s four young children were inoculated in 1721, “the distemper being in the neighbourhood.” Three survived but the youngest, aged fifteen months, died. 

The Brooksbanks wrote, “This unhappy Event may possibly expose us to the Censure of the World but the Consciousness of having done our duty to preserve life in a Time of common danger makes us easy and Content.”

Not all were easy and content. Two decades after his Philosophical Transactions article, Timone wrote a short note that hinted at the dangers of the procedure. The practice of inserting smallpox matter into an incision was quite painful, he wrote. Moreover, “it has had but ill Success.” Sometimes the patient would come down with a more severe form of smallpox; at other times, the operation appeared to have no effect at all. In addition, in some cases the incision itself became infected with “malignant ulcers” that proved fatal. 

Timone’s essay appeared in the Philosophical Transactions in 1734. Since there were no efforts to sterilize or even clean the needles used, this outcome is not surprising. Nonetheless, people in Britain and elsewhere continued to make the cost-benefit analysis, aided by Jurin’s statistics, that the risks of inoculation were far outweighed by the dangers of smallpox.

About the author:

Anita Guerrini is Horning Professor in the Humanities Emerita at Oregon State University and Research Professor of History at the University of California, Santa Barbara. Her research encompasses the history of the life sciences, medicine, and the environment since 1500. Her book The Courtiers’ Anatomists: Animals and Humans in Louis XIV’s Paris (Chicago, 2015), won the Pfizer Prize of the History of Science Society for best scholarly book. A revised second edition of her Experimenting with Humans and Animals recently appeared (Johns Hopkins, 2022). Her research has been supported by NSF, NEH, CNRS, and the American Philosophical Society, among others. She is a fellow of the American Association for the Advancement of Science, and a corresponding member of the International Academy for the History of Science. Current projects include a new biography of William Harvey for the Renaissance Lives series (Reaktion) and a book on giant fossil bones and national identities in early modern Europe. Her personal website and blog is