© Arthur Boylston, The Old Mill, Bayswater Mill Road, Headington, Oxford OX3 9SB. Email: firstname.lastname@example.org
Boylston AW (2012). The origins of vaccination: no inoculation, no vaccination. JLL Bulletin: Commentaries on the history of treatment evaluation (www.jameslindlibrary.org).
In 1796, seventy-five years after Lady Mary Wortley Montague and Charles Maitland introduced inoculation into England (Huth 2005; Boylston 2012), Edward Jenner performed an experiment that would eventually lead to the eradication of smallpox and the end of inoculation. He inoculated a child with material from a cowpox pustule just as he would have done from a smallpox pustule. About six weeks later he performed a conventional inoculation on the same child using smallpox material. When there was no reaction to the inoculation Jenner believed that he had demonstrated that cowpox could produce immunity to smallpox just like the real smallpox virus. His experiment had worked. But how did Edward Jenner get to this point, where had the ideas come from, and what lay behind his seemingly audacious practice on a defenceless child?
History texts and children’s stories all focus on the supposed role of milkmaids in guiding Jenner to cowpox. Even the most recent histories of smallpox eradication say that he learned of cowpox’s benefits from a milkmaid. In many cases the milkmaid is beautiful because she cannot catch smallpox. In some versions of this story the fabled beauty of the unscarred milkmaids is widely known and gives Jenner his first clue. Occasionally other names pop up but are quickly dispatched as not really significant and home in on Jenner as the man who realized why the milkmaids were so beautiful. Sadly the milkmaid story is a lie invented by John Baron, Jenner’s friend and first biographer (Baron 1838). Jenner himself never claimed to have discovered the value of cowpox, nor did he ever say, despite a huge volume of correspondence, how he first came across the idea. The myths of the milkmaids are just that, myths. To modern eyes, Jenner is revered for eradicating smallpox by using cowpox; in his lifetime, however, Edward Jenner faced severe criticism from jealous competitors and from many ordinary doctors who did not trust his method because, unlike inoculation, it did not give permanent immunity to smallpox. John Baron invented the milkmaid story to counteract these criticisms
What really happened is more prosaic although no less fascinating.
The Suttons’ improved method of inoculating (Sutton 1796; Boylston 2011) spread rapidly through England. By 1768 a country surgeon, John Fewster, and his colleague, Mr. Grove, had become partners with them. Years later, in response to the renowned chemist George Pearson’s inquiries, he wrote:
Thornbury was a village near Bristol on the river Severn. About six miles north is the town of Berkeley, and about seven miles inland is the market town of Chipping Sodbury. The events which led to vaccination evolved over a thirty year span in the rough triangle formed by these three Gloucestershire towns.
In 1768 nineteen year old Edward Jenner was apprenticed to Daniel Ludlow, a surgeon, based in Chipping Sodbury (Baron 1838, p 3). Daniel and his apothecary brother Edward were members of a medical society which met at The Ship, an inn at Alveston near Thornbury (Baron 1838, p 47). This was Fewster’s local medical society referred to in his letter. At one of their meetings Fewster reported his conversation with the old farmer and his subsequent inquiries so there is a potential direct connection between Fewster and Jenner through the Ludlow brothers. Fewster’s information probably spread through the West Country by word of mouth. It is just the sort of lightbulb moment that changes human knowledge forever. Before, the fact that some individuals resisted all attempts to inoculate them was a mystery and a considerable problem for doctors, since they were obliged to reinoculate their patients who had not had a smallpox pustule in response to their inoculation. Now that they had heard of cowpox on the grapevine they knew to ask their patients about cowpox, and if they did not respond to the operation there was a good explanation. The effects of cowpox would also have been of great interest to dairy workers who would have spread the information among their colleagues at fairs and market days. Within a few years the news had spread around the West Country so that most doctors and many farm workers would have heard of the phenomenon (Pearson 1798).
On one of the few occasions when Jenner discussed farmers’ knowledge of cowpox he wrote:
Here Jenner himself draws the link between inoculations with smallpox and the discovery of the effects of prior cowpox. Many years later a friend of his confirmed that Jenner once said that he first heard of cowpox in 1768 (Moore 1817, p 2).
By 1769 Jenner was in London working as a house surgeon to the famed experimental surgeon John Hunter at St. George’s Hospital. Since he discussed the cowpox effect with Hunter, Jenner must have known about the discovery before leaving Gloucestershire. But the Suttonian method only became widely available after 1766/67 (Boylston 2011) so that the discovery could only have been made in a narrow window between 1767 and 1769. while Jenner was still apprenticed to Ludlow. Whether Jenner was actually present at the dinner where Fewster discussed his findings is not clear, apprentices were probably not invited, but it seems likely that he would have heard about Fewster’s observations from his boss soon afterwards.
The advantages of cowpox could not have been discovered before general inoculation became a feature of country life, because only when large numbers of people were inoculated at the same time could the existence of several resistant individuals become apparent. Smallpox epidemics often smouldered rather than exploded and it could take months or years for the disease to leave a particular area. The few who escaped might have had previous mild smallpox and have been rendered immune by the undetected infection, something that was particularly likely to happen when the individual was an orphan because the parents, who might have remembered the early childhood infection, were dead; or they might just have been lucky and avoided exposure to the virus. John Haygarth had shown that direct contact with a smallpox patient or their possessions was necessary to contract the infection (Haygarth 1784). A few individuals, thought to be about one in twenty, seemed to be naturally resistant to smallpox and never caught the disease. Inoculation itself was also not one hundred percent effective, individuals sometimes had no response to the operation and it was common practice to reinoculate them to test whether they were resistant, immune, or whether, for unknown reasons, the first procedure had failed but the second was effective. If an individual failed to respond to inoculation after several attempts, it was usually assumed that they had had smallpox before. There was no way to link cowpox infection, which might have occurred years before and been forgotten, with inoculation resistance. However, once a large number of farmers and dairymaids were identified who resisted attempts to inoculate them it became possible to question them closely until, as Fewster relates, one of them provided the crucial piece of information. Only cowpox infection shortly before inoculation could provide the clue required, and only when a large group of individuals were inoculated together would the necessary individual turn up. Cowpox itself was a sporadic illness found mostly in the south and west of England, so the chance of finding an individual with the right sequence of infections was only turn up if a large group of dairymen was inoculated at one time.
Edward Jenner left his country apprenticeship for London where he had the good fortune to be the first pupil of John Hunter who is widely credited with developing scientific surgery. Hunter had an obsessive interest in experimentation - his most famous aphorism, which Jenner would have heard frequently, was ‘why think, do the experiment’. Master and student became close friends and remained in correspondence for the rest of Hunter’s life. When Jenner returned home to Berkeley, he took the habits of observation and experimentation gained from his mentor with him. The country physician shared some of his ideas about cowpox with his former superior who was intensely interested in the concept since he was also an inoculator.
Back home in Berkeley, Edward Jenner settled into the routine of a country doctor. He joined two local medical societies; one of them the group that met at The Ship where Fewster and the Ludlows still participated in the discussions. Why didn’t cowpox fascinate them in the way that it became an obsession for Jenner?
Fewster’s lack of interest was based on his long experience of country medicine, which had convinced him that cowpox was actually a more serious disease than inoculated smallpox. The cowpox virus was transmitted by contact, and probably could only infect through cuts or scratches in the skin. If there was only a tiny scratch then there would only be a single ‘pock’, but if there were numerous scratches all over the arms, or extensively chapped skin from continuous outdoor work, then there would be many more pustules and the patient would have a fever and pronounced systemic symptoms. Sometimes the infection even spread to the face, transferred by scratching or licking a sore finger. A few patients who had widespread skin problems might have cowpox over their whole body much like children with eczema following vaccination the 20th century. Suttonian inoculation was actually milder than natural cowpox in most cases. Fewster wrote:
In experienced hands the death rate after inoculation was less than one in five hundred, and about twenty percent of patients had only a single pock at the inoculation site. Although there was the risk of starting an epidemic, by then doctors knew how to prevent one, either by isolation or general inoculation. In contrast to inoculated smallpox, a cowpox pustule often matured into an intensely painful ulcer on the hand or fingers which left the sufferer unable to work for several days. On balance inoculation was less troublesome for the patient than having cowpox.
There was a second, and more compelling, reason why country doctors were not impressed by cowpox. It did not always protect against smallpox. Many individuals who said that they had had the cowpox before, had perfectly normal inoculation smallpox. There were also cases of natural smallpox among individuals who had thought that they were immune from a previous infection caught from cows. While immunity always implied prior cowpox, previous cowpox did not always imply immunity. What would be the point of investigating the potential benefits of something that simply was not as effective as current practice? It is easy to see why Jenner’s colleagues found him tedious, and even he acknowledged that the imperfect protection problem was a major setback, noting that the term ‘cowpox’ was also applied to conditions – ‘spurious cowpox’ – which were not infections with vaccinia (Jenner 1799).
It took Edward Jenner twenty-five years to unravel the mess. The problem lay in the definition of ‘cowpox’. There were at least three diseases that produced ulcers on the teats of cows and only one of these was caused by the cowpox virus: ‘this for a while damped, but did not extinguish my ardour’. Jenner’s remarkable achievement is that he spent all that time untangling true cowpox from spurious cowpox and defining its unequivocal appearances. He learned how to recognise ‘milker’s nodes’ a painful bacterial infection on the fingers, which lacked the typical erosive ulcer of cowpox, and he could differentiate between cowpox and staphylococcal infections of the udder because the damage caused by staphylococcal bacteria spread beyond the teats. Eventually he learned how to recognise cases of true cowpox and could confirm that they really were resistant to inoculation. Jenner had also had a second insight that his colleagues had not appreciated. Inoculated cowpox would be much less severe than natural cowpox, just as inoculated smallpox was less dangerous than naturally acquired disease.
In May 1796 Jenner was asked to inoculate an eight-year-old pauper child named James Phipps. At the same time there was a local outbreak of cowpox, something that only occurred every few years. Sarah Nelmes, a dairymaid, was infected with cowpox from her employer’s cows and had developed a large pustule where she had been scratched by a thorn.
Had Jenner done something unethical? In medical circles it is fashionable to claim that his first experiment would never have been approved by a modern ethics committee. Some writers even claim that the boy was an unwilling victim of Jenner’s ego and he would never have ‘volunteered’ for the experiment. In reality Jenner was acting in a completely acceptable way and actually giving Phipps, son of a poor labourer, protection against a feared disease. A child who had not had smallpox was almost unemployable because no one would take on a boy who might bring smallpox into the household and whose care and burial expenses would be charged to his employer if he did come down with the disease. Even if he remained in the workhouse his care would be an unnecessary expense for the parish. Inoculation was the standard way to give the child immunity and protect him from the consequences of the infection. Although Jenner had never ‘vaccinated’ anyone before he had good reason to believe that the procedure might work based on numerous patients of his who had proved resistant to inoculation after having cowpox. All he was doing was attempting to see whether artificial cowpox worked as well as natural cowpox, just as artificial inoculated smallpox protected against natural smallpox. After vaccinating Phipps he was be inoculated in the usual way. If cowpox had failed, he would just have a normal mild inoculation response; if it worked nothing would happen. Jenner was following up his experimental treatment with the ‘gold standard’ method of protecting the child. Since inoculation was a well-established and largely safe procedure that was widely used in England, there was no ethical issue with that part of the experiment. Inoculation would have been viewed as a necessary part of growing up for a child receiving parish support. Since cowpox was never fatal and had few systemic effects, there were unlikely to be any unexpected complications apart from failure to immunize. Even in the hyper health-and-safety conscious twenty-first century this experiment would have been given ethical approval.
Edward Jenner attempted to publish the Phipps experiment in a manuscript which was rejected by the Royal Society (Crookshank 1889, pp 250-266). Why would this august body turn down what we now regard as one of the most important discoveries ever made? Actually, the manuscript was a mess. Although Jenner gave short details of ten patients who had resisted inoculation several years after having cowpox, Phipps was one the only patient he had immunized with cowpox (Morabia 2010). One example was not enough to support replacing inoculation with smallpox with cowpox. When John Haygarth heard of the experiment he thought that it was potentially interesting but that one case provided insufficient evidence; twenty or thirty would be more convincing. The rest of Jenner’s paper consisted of speculations on the animal origin of cowpox; he thought that it was derived from a horse disease called ‘grease’. And he gave a rambling hypothesis that many human diseases were derived from animals and a very confusing observation that immunity seemed to work in only one direction. Cowpox prevented smallpox, but smallpox did not prevent cowpox. By rejecting the paper the Royal Society spared Jenner the criticism and derision that would have followed his weak evidence and unsupported ideas. They actually saved his reputation.
Undeterred by rejection, Jenner attempted to expand his experiment. He recognised that there were one or two problems that he needed to overcome before his idea became a useful treatment. He had shown that whatever cowpox was, it could make someone immune to smallpox. But was this a stable property of the cowpox, or would it only work when transmitted from someone who had been directly infected by a cow? In a world that had no idea what germs were, there was no way to be certain that an infection always produced the same result. Jenner believed that cowpox was derived from ‘grease’, an infection of horse’s hooves, which acquired the properties of cowpox when it infected a different species, the cow. Perhaps cowpox would also change when it was passed from person to person.
However, he could not perform any more immunizations because there was no cowpox in the neighbourhood. He had to wait until the Spring of 1798 when cowpox reappeared. This time he conducted a complicated experiment, first inoculating William Summers with cowpox, then twelve days later, using fluid from his pustule to ‘inoculate’ William Pead. Eight days later he transferred fluid from Pead to several children and adults and from one of them, Hannah Excell, he inoculated a further four children seven days after that. Finally he used fluid from one of them, Mary Pead, to inoculate a boy, J. Barge. Sometime later Jenner arranged for his nephew Henry to inoculate Summers and J. Barge with smallpox fluid which, as he expected, resulted in no reaction.
Jenner’s complicated passage of fluid from one child to another was important because it satisfied him that whatever was responsible for immunizing the children was stable and could be passed from one person to another without losing its potency. He once stated that it was the only original contribution that he made to the establishment of cowpox as a better form of inoculation (Morabia 2010). Now he was ready to publish his experiments.
Edward Jenner’s first publication about cowpox, An Inquiry Into the Causes and Effects of the Variolae Vaccinae, or Cowpox (Jenner 1798), did not arrive on a completely unsuspecting world. Jenner had discussed his ideas with many of his friends, including George Pearson who had discussed the basic concepts with John Hunter as early as 1789. However, Jenner’s paper was actually rather thin. He provided 16 cases histories of individuals who had proved to be immune to smallpox following cowpox and he had ‘cowpoxed’ at least ten others, but he had only performed a smallpox challenge on three of his subjects. Although they were immune, it was weak evidence at best.
William Woodville, physician to the Hospital for Smallpox and Inoculation, managed to find a cowpox-struck cow in London and collected material to perform his own trial assisted by George Pearson. From the beginning it was a disaster. Many of their patients developed pustules on their bodies, not just the solitary pustule at the inoculation site as Jenner had claimed. One of their five hundred patients died, which was more than the one in six to eight hundred that Woodville expected from his many years at the inoculation hospital. Woodville concluded that there was little difference between inoculated cowpox and inoculated smallpox (Woodville 1799, pp 57-59).
Jenner refuted Woodville’s claims at once. None of his patients had ever developed more than a single pustule. The problem lay in the Inoculation Hospital where the atmosphere, fixtures, and even Woodville himself, were so marinated in smallpox that he had accidentally contaminated his vaccine. When none of Woodville’s private patients, who were vaccinated away from the hospital, developed any other sores he concluded that Jenner was correct.
Although Pearson had confirmed many of Jenner’s claims about cowpox, relations between the two men soured, especially when Pearson founded a vaccination clinic in London and offered Jenner a subsidiary role in its management. The Vaccine Institute, Pearson’s project, was intended to monopolise the vaccination trade in London and generate a large private practice in vaccination for its founder. Matters came to a head in 1802 when Jenner’s friends petitioned Parliament to grant Jenner an honorarium of £10,000 to compensate him for the lost income he suffered while developing his innovation. But Jenner made a near fatal mistake. He opened his petition, claiming that he was the true discover of the benefits of cowpox (House of Commons Committee 1802, p 7). Later in the document, his nephew George corrected this, claiming instead that the person to person transmission was the original discovery which had established vaccination. Jenner’s misstatement opened the way for George Pearson. During the House of Commons investigation Pearson gave testimony that he had gathered a great deal of information implying that Jenner did not deserve the reward. His case was based on several features of Jenner’s work. Firstly, Jenner had not ‘discovered’ that cowpox prevented smallpox, this fact had been known for at least 30 years before Jenner’s The Inquiry was published. Secondly, Jenner did not understand the basis of his ‘discovery’ since he believed that ‘grease’ was the source of cowpox and claimed that he had immunised with material taken from horses’ hooves. Numerous attempts to confirm this observation had failed. A farmer named Jesty, and at least one other doctor, had inoculated with cowpox material years before Jenner so he did not deserve to claim priority. Finally, Pearson and Dr William Woodville, physician to the Smallpox and Inoculation Hospital, had been the first to confirm Jenner’s observations by initiating a large series of vaccinations, which were far superior in their value to the few cases Jenner had produced.
Most of Pearson’s comments were fair; only the claims that he and Woodville had initiated trials confirming the findings were shown to be untrue. Another physician, Henry Cline, had begun before them. Indeed, Jenner had never claimed that he had discovered the value of cowpox, nor had he claimed that he was the first to vaccinate. His claim was based on his demonstration that the agent could be passed from person to person while retaining its protective properties. Parliament found in favour of Jenner and voted to give him £10,000.
Many medical innovations divide public opinion. Immunisation has been opposed by some parts of society from its very beginnings. Opponents of vaccination (cowpox inoculation) used Pearson’s arguments to denigrate Jenner and deprecate his discovery. Pearson went so far as to invite farmer Jesty to London where he had his portrait painted. This was hung in the Vaccine Establishment as a reminder of the view that Jenner’s reputation was inflated (Pearson et al. 1805).
Much of the opposition to vaccination stemmed from the undoubted success of inoculation. Woodville admitted that the Smallpox Hospital had misled their patients into believing that they were being inoculated when they were being vaccinated because they would have refused ‘cowpoxing’. Families all over Britain had been inoculated in the great expansion of the practice brought about by the Suttons (Boylston 2011). Now parents and grandparents wanted the same well known and well regarded treatment for their own children. Country doctors who had used inoculation with great success for the whole of their careers were reluctant to give up a practice that they trusted for a less well understood innovation.
Within a decade of Jenner’s first publication it was clear that there was a major flaw in vaccination: it did not produce lifelong immunity to smallpox. Shortly after the new practice began to spread, cases of true smallpox in patients previously vaccinated appeared. At first Jenner tried to explain them away by claiming that the inoculator was an unskilled operator, or that he had used spurious cowpox to perform the operation. However, soon there were cases where there could be no explanation, other than a failure of vaccination to provide protection. Eventually even one of Jenner’s patients developed severe confluent smallpox ten years after the master had performed his vaccination. Although none of these cases had been fatal, their existence raised the possibility of severe disease. Everyone knew that sometimes smallpox was discrete and other times confluent. Parents now faced the anxiety of what to do about their vaccinated children. Should they have them inoculated to be on the safe side? To many, such failures argued that Jenner had been wrong and that vaccination was a failed experiment that should be abandoned. Since the idea that ‘grease’ was the forerunner of cowpox had been proven false, perhaps the value of cowpox was also an illusion. Jenner’s concept of ‘spurious cowpox’ was attacked. Nothing like spurious smallpox or spurious measles existed, so why believe in ‘spurious cowpox’. If that idea was also false, then all of Jenner’s arguments relying on it as the explanation for failed vaccinations were also false. Inoculators resorted to the timeless medical teaching ‘never abandon experience for experiment’.
One of the first to notice that vaccination sometimes failed was Daniel Sutton (Sutton 1796; Boylston 2011). He replied to a Royal College of Physicians circular asking for information about the success of cowpox, giving a report of two patients that he had personally vaccinated with cowpox who had subsequently developed smallpox. He was livid when the College demanded that he attend in person and bring exact details of his cases. How dare they imply that he was lying? It would be Sutton’s last public appearance where he defended what had become commonly known as ‘the Suttonian method’ in contradistinction to ‘cowpoxing’. But his treatment was a symptom of another issue surrounding vaccination. Opponents of vaccination felt that the medical establishment had sold out to Jenner and were censoring all criticism. |Eventually it would become clear that vaccination ‘wore off’ after a few years and that it only provided complete protection for 3-5 years in some individuals. But to some even this was a nuisance since inoculation provided lifelong protection.
Because vaccination would eventually prove such a huge success and lead to the eradication of smallpox it can be difficult for modern observers to realise exactly how controversial vaccination was in the early 19th century. Jenner’s reputation was under attack from several aspects. It becomes easier to understand why John Baron, Jenner’s biographer deliberately mislead posterity by publishing a truncated version of Fewster’s letter, which only included his comments that he did not think cowpox was better than smallpox. For years Jenner’s opponents had argued that Fewster, not Jenner, was the true discoverer of inoculation and Baron wanted to stamp on this claim. Fewster himself never claimed that he was the originator and remained friends with Jenner, even sending him occasional case reports to add to his collection. Yet Baron clearly took Fewster’s letter seriously enough to misrepresent its contents and to belittle Fewster’s subsequent lack of interest in cowpox when Jenner tried to raise the subject at their medical society meetings. He inadvertently confirms the likely accuracy of the account by trying to discredit it. Baron even suggests that the other members of the society threatened to banish Jenner if he did not stop his continual dialogue around cowpox. The effect of Baron’s autobiography is to characterise Fewster and his colleagues as ignorant fools who were unable to appreciate the genius of Jenner. Whatever Fewster did, it was enough to upset John Baron. Yet, despite having ample opportunity for over twenty years, Edward Jenner never refuted Fewster’s account of the discovery of the cowpox effect. Modern smallpox texts cite Fewster as an example of a discredited claim for priority and never publish the entire text of his letter. Further, some of them confuse the issue by stating that Fewster claimed to have reported his findings to a London medical society and that no published records of the event remained.
Quite where the various versions of Fewster’s actions came from is difficult to track down. Certainly there could not have been a presentation to the London Medical Society in 1765 since that organization wasn’t founded until 1776, and Fewster could not have made his discovery in 1765, as some accounts claim, because he only moved to Thornbury in 1768. These versions appear to be attempts to defuse the claims of the importance of Fewster’s role by reducing them to unpublished observations that had no impact on the subsequent development of vaccination. Baron’s creation of the milkmaid myth serves a similar purpose. In the absence of any statement from Jenner about what had really happened the Fewster letter gained credence. By planting the milkmaid story, and claiming that Jenner had told it to him more than once, Baron provided and alternative version, which he strengthened by claiming that Jenner had repeated it on his death bed.
Baron’s milkmaid fiction soon took on a life of its own. Subsequent authors attempted to explain how a milkmaid could have known that cowpox protected her from smallpox by inventing a tradition that milkmaids had singularly beautiful faces because they were not scarred by smallpox. However, no one ever commented on this at the time (the 1760’s or before) and there are good reasons to believe that it was not so. For one thing boys as well as girls milked cows in England, and no one ever suggested that cowboys had smooth complexions. Furthermore, both smallpox and cowpox occurred sporadically and there was no reason why a future milkmaid would get cowpox first. There should have been both scarred and smooth milkmaids and, again, no one noticed.
Smallpox was actually not very contagious so that during an outbreak at a farm or small farming village a few individuals would escape the infection by chance or because they were resistant to the virus (Dixon 1962, p 250). There would be no way to connect their escape to a previous attack of cowpox until artificial infection - that is, inoculation - made the link obvious.
Note: This article is based on Chapter 25 (‘The pretty milkmaids’) in Boylston AW (2012). Defying Providence: Smallpox and the forgotten 18th century medical revolution. ISBN 978-1478232452.
This James Lind Library commentary has been republished in the Journal of the Royal Society of Medicine 2013;106:351-354,395-398
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