Smallpox inoculation: prelude to vaccination

Art Boylston
Headington, Oxford, UK


Image of James Jurin secretary of the Royal Society.
Fig. 1: James Jurin secretary of the Royal Society.
Courtesy of the Royal Society

Inoculation for smallpox, now known as variolation, consisted of placing a small amount of fluid from a smallpox pustule into the skin. It was introduced into England and colonial Boston in 1721 following reports from Constantinople that the practice was safe and produced lifelong immunity to smallpox.1 Not surprisingly the idea attracted a storm of opposition. Some objected that it was not safe and did not produce immunity because the disease which resulted was not smallpox but some other distemper. Also it was immoral to make oneself ill. Inoculation interfered with divine providence; only God could determine an individual’s fate and it was a sin to subvert Providence. Proponents of inoculation had to find answers to these objections or it would never be used. While early experiments on a few children and condemned prisoners suggested that it was safe, the evidence was by no means convincing.

In the winter of 1721–22 Thomas Nettleton, a Yorkshire physician, aware of some earlier accounts of variolation, inoculated over thirty people in the parish of Halifax, all of whom developed mild smallpox and survived. In April 1722 he wrote to a friend in London who passed his letter to James Jurin, secretary of the Royal Society.2 Jurin initiated a correspondence with Nettleton3 who replied to Jurin’s request for further information in a letter dated June 16, 1722:4

Sir, I doubt not that when you have collected a sufficient Number of Observations … you will be able to demonstrate, that the Hazard in this method is very inconsiderable, in proportion to that in ordinary way by accidental Contagion, so small that it ought not to deter any Body from making use of it.5

To satisfy himself that his assertion was correct Nettleton had collected figures for smallpox deaths in parts of Yorkshire. He found that 270 of 1,245 patients with smallpox had died, while none of the sixty that he had inoculated had succumbed.

Jurin recognized that Nettleton’s suggestion was the best way to answer the question “was inoculation safer than natural smallpox?” and set about collecting more data. In December Nettleton wrote again sending details of 3,405 cases of smallpox6 to which Jurin added 1,221 cases he had collected from two sites in Britain. A total of 856 patients out of 4,626 suffering from natural smallpox had died. Only two out of 182 inoculated in the same parts of Britain had succumbed.7

Jurin’s use of mortality as a marker for safety meant that the outcomes were unequivocal. While physicians might argue about the severity of individual cases making comparisons difficult, death was an absolute marker. To strengthen the evidence Jurin circulated an advertisement asking anyone with experience of inoculation or natural smallpox to send the details to him at the Royal Society. Between 1722 and 1729 over 129 letters arrived at the Royal Society giving details of both forms of smallpox. Jurin would publish the results each year.

 Image of 18th century inoculation lancets.
Fig.2. 18th century inoculation lancets.
Photo courtesy of

In the first of his annual reports, covering 1723, he set out the rationale for his project. There were two questions that would determine the fate of inoculation: was it safer than natural smallpox and did it produce long-lasting immunity. “If either of them be fairly determined in the Negative, the Practice of Inoculation must on all Hands be given up.” On the other hand, “if the Practice of Inoculation be really found to be a Means of Preserving Life, it will not be easy to make the World believe that it is criminal to use it” and all physicians should declare themselves in favor of the practice.8

As to lifelong immunity, this could only be demonstrated over a long period of time, but all attempts to cause inoculated individuals to develop a second attack of smallpox by exposing them to patients with the most severe, fatal forms of the disease had failed. Jurin would pursue every claim of smallpox following inoculation and showed they all were false.

When Jurin resigned from the secretaryship of the Royal Society the inoculation project was carried on by John Gasper Scheuchzer who produced a report in 1729 bringing together the results of all the inoculations known to the Royal Society and the figures for mortality from natural smallpox.9 Only 26 of the 1,087 inoculated individuals had died, while 3,008 of 18,229 people with natural smallpox perished. Scheuchzer concluded, “upon the whole it is submitted to the Judgement of every impartial and well meaning Person, who will be at the trouble fairly and maturely to weigh the several matters of Fact here laid down, and the Consequences drawn from them, whether the Practice of Inoculation ought to be rejected as dangerous and uncertain; or whether it doth rather deserve Commendation and Encouragement, as salutary and greatly beneficial to Mankind.”10

The results of the Royal Society’s inoculation project formed the basis for a rational decision by individuals and medical practitioners. They could chose between two levels of risk. Differential risk was also cited as refuting the religious argument that an individual had no right to chance his life by undergoing a potentially dangerous procedure. Cotton Mather used numbers to turn the argument around. Since inoculation was clearly safer one was obliged to use it rather than risk the higher mortality of natural smallpox.11

One remarkable feature of these inoculation studies was the belief that future events were predictable. Mortality of the two forms of smallpox would remain constant rather than subject to massive, unpredictable variations. Although never explicitly stated as such, the numbers suggested to 18th century observers that divinely ordained natural law underlay the outcome.12 Just as Newton’s mathematics had defined the laws of motion, so experience defined the relative safety of both natural and artificial smallpox.

Within ten years the evidence supporting inoculation was used on a number of occasions to justify its use to halt epidemics. In Boston in 1730,13 Bury St. Edmunds in 1732,14 and the Thames valley in 1737,15 inoculation was advocated based on the evidence developed by Jurin and the Royal Society. Thus there was immediate practical as well as theoretical value, derived from comparing the two way of contracting smallpox.

The deliberate use of quantitative evidence to guide decisions marks out inoculation as an example of enlightenment thinking. One could choose one’s fate. Risk smallpox, or defy providence and be inoculated. What could be more enlightened?

Image of book on Scheuchzer’s Account of Inoculation between 1721 and 1728.
Fig.3. Scheuchzer’s Account of Inoculation between 1721 and 1728.

In the early 1760s the Sutton family revised the technique used to inoculate and allowed their patients free access to fresh air and the outdoors.16 Their innovations made the practice less painful, safer, more convenient, and cheaper. They formed partnerships with local practitioners across England, in the colonies and on the continent. Groups of patient could be gathered in large houses rented for the purpose and inoculated together. In one such group inoculation, in the village of Buckover in Gloucestershire, the surgeon, John Fewster, noted that several farmers were resistant to inoculation.17 Since they all denied having had smallpox there was no satisfactory explanation for their lack of response until one old farmer said “I have had cowpox quite severely, if that makes any difference” and Fewster says “we took the hint.”18 All the resistant farmers had had cowpox. Fewster communicated his findings to his local medical society where the Ludlow brothers, to whom Edward Jenner was apprenticed, were members.19 This, not a milkmaid, is how the benefits of cowpox were discovered. Edward Jenner realized that cowpox could be substituted for smallpox to induce immunity and eventually worked out the details that allowed him to promote vaccination. Even Jenner says that cowpox could not have been discovered before the Suttons’ improved method of inoculation extended the practice to the common people.20,21

Smallpox and cowpox were both sporadic diseases in the West Country.22 There was little chance that an outbreak of cowpox, usually confined to a single farm, would have occurred just before smallpox arrived at the same community revealing that cowpox prevented smallpox. Inoculation of several individuals together was the only way that the relationship of one disease to the other could be unveiled. Furthermore the two methods of immunizing were identical apart from the infectious material on the lancet. Inoculation was so widely known and trusted that vaccination seemed to many people to be only a small change and therefore not threatening. The quantitative demonstration of the relative safety of inoculation in the 1720s established a platform from which vaccination could be launched. Immunization and vaccination were so similar that there was no need for detailed quantitative studies of vaccination. Resisting inoculation after vaccination was acceptable proof of immunity.

After Edward Jenner introduced vaccination inoculation came to be regarded as a dangerous, outmoded, and now unjustified procedure. Indeed inoculation persisted in parts of Africa and the Indian subcontinent into the 1970s and became a significant barrier to the eradication of smallpox.23 The myth that Jenner had been told about cowpox by a milkmaid eliminated a role for inoculation in the eventual eradication of smallpox. The milkmaid story, invented after Jenner was dead by his biographer John Baron,24 broke the link between inoculation and vaccination. Vaccination seemed to have arrived out of the mists of folklore. Inoculation was seen as a sterile stage in medical history, neither important nor interesting. Inoculation got written out of the history of smallpox and its role as the direct progenitor of vaccination became lost. But without inoculation there would have been no vaccination.



  1. Genevieve Miller. The Adoption of Inoculation for Smallpox in England and France (Philadelphia: University of Pennsylvania Press. 1957).
  2. Thomas Nettleton A Letter from Dr, Nettleton Physician at Halifax in Yorkshire to Dr, Whitaker concerning the Inoculation of the Smallpox Philosophical Transactions of the Royal Society XXXII no 370 (1722a)  35.
  3. Thomas Nettleton. From Thomas Nettleton in Andrea Rusnock ed The Correspondence of James Jurin (1684-1750) Amsterdam Rodopi  (1996) 98>99. The original is missing but is referred to in this letter.
  4. Thomas Nettleton. A letter from the same Learned and Ingenious Gentleman concerning further progress in Inoculating the Smallpox. Philosophical Transactions XXXII no 370 (1722b) 49.
  5. Thomas Nettleton 1722b 51.
  6. Thomas Nettleton Part of a Letter from Dr. Nettleton, Physician at Halifax, to Dr. Jurin R.S. Secr. Concerning the Inoculation of the Smallpox and the Mortality of That Distemper in the Natural Way. Phil Trans XXXII (Nov-Dec 1722) no 374. 209.
  7. James Jurin. A letter to the Learned Dr. Caleb Cotesworth containing a Comparison between the Danger of the Natural Smallpox and that Given by Inoculation. Phil Trans XXXII (Nov-Dec 1722) 374. 213.
  8. James Jurin. An Account of the Success of Inoculating the smallpox in Great Britain with a Comparison between the Miscarriages of that Practice, and the Mortality of Natural Smallpox. London, J.Peele at Lock’s Head  in Paternoster Row (1724) 3>4.
  9. John Gaspar Scheuchzer. An Account of the Success of Inoculating the Small Pox in Great Britain for the years 1727 and 1728. London. J Peele at Lock’s Head in Paternoster Row (1729).
  10. Scheuchzer, An Account 38.
  11. Cotton Mather. Sentiments on the Small Pox Inoculated. Reprinted from the original folio single sheet printed at Boston in 1721. With an Introduction by George Lyman Kittredge. Cleveland Printed for Private Distribution (1921).
  12. Jurin 1724 32>33.
  13. John B. Blake Smallpox inoculation in Colonial Boston. Journal of the History of Medicine and Allied Sciences VIII (1953) 284.
  14. David Hartley. Reasons Why the Practice of Inoculation Ought to be Introduced into the town of Bury at present. Bury St. Edmunds (1733).
  15. Anonymous. Of Inoculating the SMALL POX; occasioned by its now raging in several large Towns. Gentleman’s Magazine 7 (1737) 561.
  16. J. R. Smith. The Impact of Daniel Sutton in J.R. Smith The Speckled Monster. (Chelmsford: Essex County Record Office. 1987).
  17. Abstract of a Letter from Mr. Fewster, Surgeon in Thornbury, dated October 11th, 1798 to Mr, Rolph, Surgeon in Peckham. In George Pearson, An Enquiry concerning the History of the Cow Pox (London: J. Pearson no 72 St. Paul’s Churchyard. 1798) 50>51reprinted in Edgar March Crookshank History and Pathology of Vaccination vol. II. (London: H.K. Lewis 1889) 84>85.
  18. J.Fewster ibid.
  19. John Baron. The Life of Edward Jenner (London: Henry Colburn , Publisher, Great Marlborough Street. 1838) 47>51.
  20. Edward Jenner. The origin of the Vaccine Inoculation (London: D.N. Sheen, Berwick Street, Soho. 1801) 1.
  21. Fewster is misrepresented in all modern accounts of smallpox. It is usually stated that he noticed the cowpox effect in 1765 and reported it to the London Medical Society but never published the finding and so it is not relevant to Jenner. I have been unable to find a use of this argument before 1962. See C.W. Dixon. Smallpox. (London: Churchill. 1962) 249>252. A fuller account of the Fewster letter can be found in Arthur William Boylston. Defying Providence; Smallpox and the forgotten 18th century medical revolution, (self published 2012.
  22. Derrick Baxby. True and Spurious Cowpox  in Derrick Baxby, Jenner’s Smallpox Vaccine (London: Heinemann Educational Books. 1981) 134.
  23. F. Fenner, D.A. Henderson, I. Arita, Z. Jezek, I.D. Ladnyi. Smallpox and Its Eradication. (Geneva: World Health Organization. 1988).
  24. Baron, The life 121>122



ART BOYLSTON, MD, graduated from Yale College and Harvard Medical School and trained in pathology at the Peter Bent Brigham Hospital, the NIH, and St. Mary’s Hospital London. He is emeritus professor of pathology in the University of Leeds. He now lives in Oxford and is a senior research fellow of the Centre for Editing Lives and Letters (CELL) at University College London. He is the author of Defying Providence-smallpox and the forgotten 18th century medical revolution (2012: Create Space).