***
Fortunately for us all, Edward Jenner recovered from the trauma of his experience with variolation and the road to salvation for generations of people began five years later, when at the age of thirteen he embarked on his long and exceptional medical career. It was common in those days for doctors to learn their craft by apprenticeship and Jenner went to work with Dr Daniel Ludlow, an eminent country surgeon who lived near Bristol. It soon became obvious that Jenner had a sharp and enquiring mind and he was a keen observer and listener, storing away many things that would later inform his research.
During his training, Jenner was reminded of another commonly held belief in regard to smallpox. He heard a dairymaid say, ‘I shall never have smallpox for I have had cowpox. I shall never have an ugly pockmarked face.’[20] In rural areas of England and Europe it was well known that milkmaids became immune to smallpox after developing cowpox, which they caught because of their close contact with cows. Cowpox was not dangerous to humans and cows exhibited few symptoms other than pox or pustules on their udders accompanied by a slight decrease in milk production. This phenomenon had been noted by the medical profession and in 1765 a doctor from Gloucestershire reported to the Medical Society of London that people who had had cowpox had no reaction to variolation with smallpox material.
It was to be an odd marriage. Folklore was to become the foundation for the science that Edward Jenner would use to develop the first vaccine. As we understand it today, a vaccine which can be given by injection or orally consists of live, attenuated—meaning weakened in some way—or killed disease-causing micro-organisms, or in the case of some vaccines just a fragment of the organism’s specific protein. Proteins are compounds that are essential constituents of all living organisms. A vaccine works by stimulating a person’s immune system which then produces antibodies against that disease, thus killing or neutralising the infectious micro-organism.[21] Vaccines can be prophylactic, which means they prevent or ameliorate the effects of a future infection; or therapeutic, meaning they cure the disease after it has been contracted.
All that is now known about disease prevention by vaccination follows from Jenner’s fundamental work, work that he did before medical science had an understanding of microbiology and immunology.
In 1770 Edward Jenner began further medical training at St George’s Hospital in London under the tutelage of Dr John Hunter, a leading surgeon and a pioneer of medical practice. Hunter had a profound influence on Jenner’s life. He became aware of Jenner’s observational and investigational skills and taught his protégé not only surgical techniques but, more importantly, the use of scientific method, insisting that the young physician’s medical practices and decisions be based on evidence. As a result Jenner developed a rigorous and methodical approach to scientific investigation. He would carefully make observations from his own experience, form a hypothesis, test it and modify it to make new predictions which in their turn were tested. His method provided the scaffolding for his own research and for future discoveries as well.
Hunter also fostered Jenner’s great love of nature and natural science, encouraging him to assist the botanist Joseph Banks in classifying the botanical specimens he collected on Captain James Cook’s expedition in search of Terra Australis Incognita.[22] Cook was the first European to explore the east coast of Australia, and Jenner was invited to join Cook’s 1772 expedition as a botanist but turned the offer down. At the age of 23 Jenner returned home to Berkeley to take up the position of local doctor. The scene was set for a medical breakthrough that would change the world.
In his practice at Berkeley Jenner was frequently asked to variolate people against smallpox. He would insist that patients rest and maintain a strict diet for two weeks before the procedure. Jenner’s method was to draw up a small quantity of fluid from a smallpox pustule with a lancet, and then, being careful not to draw blood, introduce it between the outer and inner layers of the skin of the upper arm of the patient. Ever the astute observer and listener, Jenner found that some of his patients were completely resistant to smallpox variolation and deduced that these patients had previously had cowpox.
It seems that by 1788, Jenner was convinced of the scientific truth of what was considered folklore. Jenner made a crucial connection: cowpox not only protected against smallpox but could be transferred from one human being to another to provide protection. At the time he drew sketches of cowpox marks on a milkmaid’s hand and showed them to Hunter and other experts with whom he discussed the hypothesis he was forming, but the breakthrough would come a decade later after Jenner had embarked on marriage and family life.[23]
Edward Jenner may have been a country doctor but he was an extraordinarily talented and compassionate man with a universal outlook. As a response to the slave trade and the transportation of 18 million Africans he composed an anti-slavery song. He was fascinated by passenger-carrying hydrogen balloons so began building his own. He was an expert in natural history and wrote several scientific studies, the most outstanding of which, Observations on the Natural History of the Cuckoo, published in 1788, earned Jenner the honour, at the age of 35, of being named a Fellow of the Royal Society.
It was also in 1788 that Edward Jenner married Catherine Kingscote. Catherine, who with her introverted nature was the opposite of her outgoing husband, dedicated her life to her religion, to Jenner and his work and practice in Berkeley, and to their three children.
A confluence of circumstances in 1796 gave Jenner an opportunity to test his cowpox theory. In May, a milkmaid named Sarah Nelmes came to see her local doctor because she had a rash on her hand. Sarah was relieved when Jenner diagnosed not smallpox, as she had feared, but cowpox. She had caught it from one of her cows, Blossom, a name now as famous as Sarah’s.[24] Wasting no time, on 14 May Jenner extracted fluid from the cowpox pustule on Sarah’s hand and inoculated his gardener’s son, James Phipps. James was eight, the same age Jenner had been when he was variolated. Jenner made two half-inch incisions on James’ arm, rubbed the fluid in and then anxiously watched and waited. After a few days James became mildly ill with cowpox, developed a few pustules and a mild fever but was well again a week later.
This was the first step. Jenner had confirmed that cowpox could pass from person to person as well as from cow to person. But would cowpox protect James Phipps from smallpox? On 1 July 1796 Jenner variolated the boy with smallpox. As Jenner had anticipated, and undoubtedly to his great relief, James did not develop the disease, either on this occasion or subsequently when Jenner repeated the procedure a number of times to prove that James Phipps was immune to smallpox.
It is accepted, however, that Edward Jenner was not the first person to use the material from cowpox in the hope of providing immunity to smallpox. A farmer named Benjamin Jesty from Yetminster, who had survived smallpox as a child, is given that accolade. Aware of the folklore surrounding dairymaids and cowpox, Jesty inoculated his family with cowpox material during a smallpox epidemic in 1774. As the disease raged through the surrounding countryside Benjamin feared that his pregnant wife Elizabeth, his baby daughter and two sons who were aged two and three would be stricken.[25]
When Jesty heard of an outbreak of cowpox on a nearby farm he immediately took his wife and sons there, leaving the baby behind as she was considered too young for what he was planning. Jesty then collected infected pus from a cow’s udder and inserted it into a scratch he made with a stocking needle on Elizabeth’s arm. His sons were next. All three developed cowpox and although Elizabeth became quite ill, probably from an infection, the two boys were soon well again. None of the Jestys caught smallpox during this epidemic or in later ones and Elizabeth recovered and lived for another 50 years. Several years after the cowpox inoculation, so the story goes, the family underwent variolation with smallpox and none of them suffered any ill effects from this either. Despite the success of his experiment Benjamin Jesty soon realised that he had risked more than his family. People were superstitious and they believed that E
lizabeth and her sons would grow horns and turn into cows and Benjamin was reviled as some kind of sorcerer. It is little wonder that his inoculation method did not find favour amongst his neighbours. Years later the Jesty family moved to the Isle of Purbeck and in the parish church at Worth Matravers there is an inscription on one Mary Brown’s memorial tablet stating that her mother, Abigail, had been inoculated by Benjamin Jesty.[26]
A similar incident occurred in Holland in 1791. A Dutch schoolmaster named Peter Plett, who was employed as a tutor for a family in Hasselberg in Holstein, had been told by milkmaids that cowpox protected them against smallpox. He inoculated his employer’s two daughters and another child with material taken from cows that had cowpox. These children were amongst the few survivors of a smallpox epidemic that swept through Holstein three years later.[27] Apparently Plett was deterred from performing any other inoculations because the hand of one of the children had become severely inflamed. As was the case with Elizabeth Jesty this was probably caused by an infection.
These early ‘experiments’ predated Jenner’s inoculation of James Phipps and demonstrated that serum from a cow infected with cowpox could protect people from smallpox without them ever risking death through variolation with a virulent strain, but it was Edward Jenner who proved this scientifically and produced a vaccine which effectively combated smallpox. At the end of 1796, Jenner sent an article to the Royal Society describing the experiment with James Phipps and his earlier observations of thirteen people who had previously had cowpox and who after being variolated with smallpox had had no reaction.
And so began Jenner’s struggle to have his work on the efficacy and safety of cowpox inoculation in preventing smallpox recognised and accepted. So much was at stake. Jenner was offering the world a miracle, a chance to defeat the great scourge that had afflicted humans since ancient times. Instead of accolades, he received his first rebuff. Sir Joseph Banks, president of the Society at that time, rejected Jenner’s article for publication in the journal Philosophical Transactions despite the fact that two manuscript reviewers had strongly recommended it for publication.[28] An even greater insult was that the Council of the Royal Society, the same society of which Jenner was a Fellow, dismissed his research as being ‘in variance with established knowledge’ and not credible. He was warned not to ‘promulgate such a wild idea if he valued his reputation’.
Jenner was bitterly disappointed and also frustrated because there were no new cases of cowpox in the vicinity of Berkeley until the spring of 1798, which meant his experiments had been put on hold. Armed with new material Jenner substantially revised his manuscript and, on the advice of friends, avoided further insults and financed its publication himself. The title of this groundbreaking 75-page book was almost as long as the book itself: An Inquiry into the Causes and Effects of the Variolae Vaccinae, a Disease, discovered in some of the Western Counties of England, particularly Gloucestershire, and known by the name of The Cow Pox.
Jenner used the term ‘Variolae Vaccinae’ for cowpox, and from this the word vaccination is derived. Vaccinae comes from the Latin word vacca meaning ‘cow’. Cowpox was also called ‘vaccinia’. It was in 1803 that ‘vaccination’ entered the English language when Richard Dunning, a surgeon in Plymouth who had performed many cowpox inoculations, as they were called, coined the term that is now used universally.
In his book Inquiry, Jenner described 23 successful vaccinations. He also described a reaction now known as anaphylaxis, an allergic hypersensitivity of the body to a foreign protein or drug. He presented evidence that cowpox material could be transferred from person to person to provide protection against variolation with smallpox. He wrote, ‘These experiments afforded me much satisfaction, they proved that the matter in passing from one human subject to another, through five gradations, lost none of its original properties.’[29] Far in advance of his time, Jenner suggested cowpox diseases were caused by some kind of infectious entity that he called a ‘virus’, not a virus in the modern sense of a micro-organism, but in its older sense meaning some kind of a poison.
After the publication of Inquiry in 1798, Jenner was fiercely attacked for a second time. Even though his results were confirmed by other physicians within the space of a year, the barrage persisted and Jenner’s new technique did not catch on as quickly as he had anticipated and hoped. Firstly, cowpox did not occur widely and doctors who wanted to test the new process had to obtain cowpox matter from Jenner. Also there was a mixed response from the medical profession. While some physicians were merely sceptical, others who derived large incomes from variolation were suddenly threatened by Jenner’s seemingly safer and more effective cowpox treatment. Another cohort was motivated by bitter professional jealousy. They responded with public ridicule.
A treatise written by Dr Benjamin Moseley in 1799 mocked Jenner’s work, referring to cowpox inoculation as ‘cowmania’ and ‘cow’s syphilis’, suggesting that like syphilis it could affect the brain. Dr William Rowley reported that after being inoculated with cowpox one child had developed an ox-faced deformity and another had developed mange, an animal skin disease.[30] Not only was the medical fraternity polarised but so too was the community. Some religious leaders denounced cowpox and people became fearful of the physical and religious consequences of being inoculated with material from what they considered God’s lowlier creatures. Wild rumours spread that people had sprouted horns after being vaccinated. Political cartoonists made the most of the hysteria and published engravings of human bodies with cows’ heads.
While fending off widespread scorn Jenner moved to London to gather volunteers for his cowpox vaccination program. After three months Jenner had made little progress but found some comfort in the fact that other physicians were succeeding where he failed. Henry Cline, Chief of Surgery at St Thomas’ Hospital, was a personal friend and Jenner had provided him with cowpox material. In return Cline offered Jenner £10,000 if he would relocate his practice to London. This was a veritable fortune but Jenner declined the offer. At this stage of his life he was financially independent having inherited land and property. In a letter to another friend Jenner wrote that he did not need more money and that at no point would he attempt to enrich himself through his discoveries. Jenner’s motives were truly altruistic.
At the London Smallpox and Inoculation Hospital William Woodville carried out extensive trials of Jenner’s treatment, vaccinating approximately 600 people in the first six months of 1799. Many of his patients developed rashes that were not consistent with those exhibited by Jenner’s patients and some contracted smallpox, which Jenner attributed to the use of contaminated lancets. Because the risk of infection was not properly understood the same lancets were used for both variolation and vaccination. It was also probable that mistakes were made during the development of the vaccine because smallpox rashes could be confused with cowpox rashes. This was later proven to be the case but initially led to claims that cowpox inoculation was no safer than smallpox variolation. It was an inexact science.
It was George Pearson from St George’s Hospital who confirmed Jenner’s findings. Pearson founded the Institute for the Inoculation of the Vaccinae and sent Jenner an invitation to the inauguration. When Pearson offered Jenner membership of the institute, Jenner was incensed believing not only that he should be in charge but that Pearson was trying to take credit for the discovery as well.[31] The politics of the time were particularly nasty, but as well as enemies, Jenner did have influential friends and they took action to have the institute boycotted.
Despite the personal and professional turmoil, a determined Jenner continued to experiment and publish results during this period. The title of one of his papers, A Continuation of the Facts and Observations Relative to the Variolae Vaccinae, was a message to his critics whose science was questionable. Jenner’s fame spread rapidly. In 1800, the novelist Jane Austen wrote that she had attended a dinner party at which her host and hostess read one of Jenner’s pamphlets on cowpox. Widespread interest
reflected how important variolae vaccinae was in combating the ubiquitous and vicious smallpox disease and this was confirmed on 7 March 1800, when the Earl of Berkeley presented his local doctor, Edward Jenner, to the King of England. Jenner was granted permission to dedicate the second edition of An Inquiry into the Causes and Effects of Variolae Vaccinae ‘To the King’.[32]
Only two years after the first publication of Inquiry the medical community had begun vaccinations on a large scale. As a result, deaths from smallpox plummeted. By the end of 1800 more than 5000 people in England had been successfully vaccinated using cowpox fluid and in Europe vaccination had reached over 100,000 people. In July 1800 the first vaccinations were carried out in the United States. Benjamin Waterhouse, a professor at Harvard Medical School, vaccinated his five-year-old son and six servants using vaccine from England. Soon after, President Thomas Jefferson organised the vaccination of his family and neighbours. In December 1801, Little Turtle, chief of the Miami tribe and several of his warriors were vaccinated in Washington DC, after Thomas Jefferson convinced them that ‘the Great Spirit had made a gift to the white men in showing them how to preserve themselves from the smallpox’.[33]
For the saviour himself, however, life had become a series of ups and downs. In addition to the criticism and jealousy that he endured during his time in London while trying to establish his vaccine, Jenner suffered due to the separation from Catherine and his children, and because he was unable to continue his private practice. In a reversal of fortune he had amassed by 1802 an enormous debt of £12,000. Friends rallied and lobbied parliament on his behalf and after much debate Jenner was granted £10,000. His rivals were again vociferous, especially George Pearson who claimed that he was more deserving of a grant because he had inoculated many more people than Jenner, but his sniping went unheeded.[34]
Smallpox, Syphilis and Salvation Page 3