Late great engineers: Edward Jenner

Towards the end of the 18th century an English doctor by the name of Edward Jenner conducted an experiment on an eight-year-old boy that was to change the world. The experiment had its critics. The clergy said that Jenner’s work was repulsive and ungodly, while satirical cartoons appeared showing humans sprouting cows’ heads. But the advantages of using cowpox pus to inoculate against smallpox – the deadliest disease in human history – soon became clear, and Jenner’s pioneering work in the field became the rock upon which the fight against smallpox and other infectious human diseases was built. While Jenner wasn’t alone in realising that inoculation with cowpox provided immunity to smallpox, he was the first to publish proof of its efficacy and to develop a reliable vaccine. Today, the physician from Berkeley in Gloucester is known throughout the world as the father of immunology. Napoleon called Jenner “one of the greatest benefactors of mankind.”

Born in the mid-18th century on 17th May 1749, Jenner came into a world of fundamental change, so much so that Britain was just about to adopt the new Gregorian calendar that corrected errors in the former Julian calendar. It was a time when British medical practice and education was undergoing a quiet revolution in which the old demarcation between the Oxbridge physicians and the more hands-on apothecaries was becoming blurred. It was a time when practical experimentation and hospital work came to be regarded as being on an equal footing with academic research. It was also at time when the smallpox virus was killing 400,000 people per year in Europe. In Britain alone smallpox accounted for the lives of ten percent of the population, with this figure doubling in urban areas where infection spread more easily.

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By Jenner’s time ‘variolation’ – treatment of a disease with the same disease to create immunity to itself – was the widespread method of addressing smallpox. While it had some impact on reducing the effect of the virus, especially among the wealthy, the process was fraught with risk, not least in that those inoculated with the disease became carriers and could infect those around them. It wasn’t until Jenner’s cowpox-based vaccination became common practice by the end of the 19th century that any significant reduction in incidence in Europe and North America occur. Even then the disease remained largely unchecked in other parts of the world, notably Africa, well into the 20th century, before intensive containment measures and scientific surveillance eventually led to its formal eradication on 9th December 1979. Four decades on, smallpox remains, in the words of World Health Organization Director-General Tedros Adhanom Ghebreyesus, “the only human disease ever eradicated.”

The part Jenner was to play in this eradication could not necessarily be predicted from his conventional background. The eighth of nine children, his father was the vicar of Berkeley, which meant that he was destined for a robust provincial education in both Wooton-under-Edge and Cirencester. By the age of 14 he had been inoculated against smallpox by variolation and he had left school, apprenticed to the surgeon Daniel Ludlow for seven years, and from whom he gained sufficient experience to become a surgeon himself. At the age of 21, Jenner undertook a further apprenticeship in surgery and anatomy at St George’s Hospital in London. It was at this time that Jenner fell under the influence of surgeon John Hunter, who offered the young doctor the characteristic Age of Enlightenment advice: “don’t think; try.” With this presumably still ringing in his ears in 1773, at the age of 24, Jenner returned to his Gloucester home where he became a practicing doctor and surgeon.

Meanwhile, English physician John Frewster had discovered that prior infection with cowpox rendered a person immune to smallpox. Also, in the 1770s, at least five simultaneous investigations were underway in Europe and Britain testing cowpox vaccination on humans against smallpox. In Britain, during the 1774 smallpox epidemic, Dorset farmer Benjamin Jesty successfully vaccinated his wife and two children with cowpox, and it is thought that Jenner may have been aware of Jesty’s work. Where Jenner comes into the story is that he managed to tie up some of the unknowns in his own research.

It had long been common knowledge that milkmaids were somehow immune to smallpox due to their routine proximity to cows and cowpox. Jenner’s hypothesis was that the well-known folklore of milkmaid immunity stemmed from the pus in the blisters they received from the less dangerous cowpox. To test this, on 14th May 1796, Jenner inoculated James Phipps, the eight-year-old son of his gardener. Jenner got pus samples from cowpox blisters on the hands of milkmaid Sarah Nelmes who had caught the disease from a cow called Blossom. Phipps presented with fever, but no full-blown cowpox infection, and so Jenner went to the next step of  challenging the boy’s supposed immunity with the variolous material (ie smallpox itself) that had to date been the standard basis of inoculation. As no disease followed, Phipps’s immunity to smallpox was challenged repeatedly. The significance of these procedures is that they made significant inroads into proving not just that cowpox could provide immunity to smallpox, but that the protective cowpox pus could be effectively inoculated from person to person and not just directly from cattle. Jenner coined the term ‘vaccination’ that linguistically has its roots in the Latin adjective vaccinus, meaning ‘of, or related to, cows.’

Jenner pressed on with his research and in 1798 published a monograph entitled An Inquiry into the Causes and Effects of the Variolæ Vaccinnæ, which was followed in annual succession by three further papers developing his ideas on vaccination. But it was to be a long and difficult road to having the concept of vaccination accepted as an alternative to variolation as the standard for smallpox prevention, with the medical establishment dithering for decades over the idea. Eventually, some 17 years after Jenner’s death, the British government banned variolation and provided optional vaccination using cowpox free of charge under the Vaccination Act 1840. It would be a further 12 years before vaccination became compulsory. Despite not living to see the full effects of his work, Jenner knew enough of his success to reflect that, “the joy I felt as the prospect before me of being the instrument destined to take away from the world one of its greatest calamities was so excessive that I found myself in a kind of reverie.”

Although Jenner might have cashed in on his success, having been widely honoured for his pioneering role in the emerging field of immunology, his single-minded focus on his work on the understanding of vaccination and vaccines meant that his country medical practice fell into neglect and suffered financially. To ensure his research into vaccination could continue, in 1802 Jenner’s colleagues, with the support of King George III, petitioned the British government for a grant of £10,000 (approximately £1m today), which was followed five years later by a further £20,000 after the Royal college of Physicians had confirmed the widespread efficacy of vaccination. In 1803 he became president of the Jennerian Society established to promote vaccination to eradicate smallpox, and in 1805 he became a founding member of the Medical and Chirurgical Society, that was to become the Royal Society of Medicine. By 1821 such was his influence that he became physician to the new king George IV and mayor of his hometown of Berkeley, where he is buried having died of stroke in 1823.

Although the disease may have been eradicated, there remain two official samples of the virus known to cause smallpox kept in tightly controlled WHO-sanctioned government laboratories in the United States and Russia. Their existence periodically raises the ethical debate over whether they should be destroyed, with the current position of both countries being outlined by the former Secretary of the U.S. Department of Health and Human Services, Kathleen Sebelius, who says that the dangers of destroying the samples outweigh the ‘minuscule risk’ attached to keeping them. Their destruction, she says, would be purely symbolic and could leave the world vulnerable should we ever need to conduct further scientific research into the virus.

Jenner’s legacy is best articulated in the opening sentences of a resolution by the World Health Assembly published on 8th May 1980 that “declares solemnly that the world and its peoples have won freedom from smallpox, which was a most devastating disease sweeping in epidemic form through many countries since earliest time, leaving death, blindness and disfigurement in its wake…”