May 142015
 

NPG 62; Edward Jenner by James Northcote

On this date in 1796 Edward Jenner administered his first smallpox vaccination. I love the fact that he was also the first person to describe the brood parasitism of the cuckoo. Jenner was born in Berkeley, Gloucestershire, as the eighth of nine children. His father, the Reverend Stephen Jenner, was the vicar of Berkeley, so Jenner received a strong basic education. He went to school in Wotton-under-Edge and Cirencester. During this time, he was inoculated (NOT vaccinated) for smallpox, which had a lifelong effect upon his general health.

Let’s take time out to talk about inoculation versus vaccination – terms which are now confused. Inoculation, also called variolation, is the act of introducing the SAME pathogen into an individual as the one you want to immunize against. So, for example, some parents deliberately have their children play with ones with chicken pox so that they will catch the disease and in future be immune. This is inoculation. Vaccination is introducing a DIFFERENT pathogen to create immunity. Jenner was inoculated, that is, he was given a mild case of smallpox to immunize him. This can be effective but it is dangerous, and can be lethal.

At the age of 14, he was apprenticed for seven years to Daniel Ludlow, a surgeon of Chipping Sodbury, South Gloucestershire, where he gained most of the experience needed to become a surgeon himself. In 1770, Jenner became apprenticed in surgery and anatomy under surgeon John Hunter and others at St George’s Hospital. William Osler records that Hunter gave Jenner William Harvey’s advice, very famous in medical circles (and characteristic of the Age of Enlightenment), “Don’t think; try.” Hunter remained in correspondence with Jenner concerning natural history and proposed him for the Royal Society. Returning to his native countryside by 1773, Jenner became a successful family doctor and surgeon, practicing on dedicated premises at Berkeley.

Jenner and others formed the Fleece Medical Society or Gloucestershire Medical Society, so called because it met in the parlour of the Fleece Inn, Rodborough (in Gloucestershire), meeting to dine together and read papers on medical subjects. Jenner contributed papers on angina pectoris, ophthalmia, and cardiac valvular disease and commented on cowpox. He also belonged to a similar society that met in Alveston, near Bristol.

Jenner was elected Fellow of the Royal Society in 1788, following his publication of a careful study of the previously misunderstood life of the nested cuckoo, a study that combined observation, experiment, and dissection.

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His description of the newly hatched cuckoo, pushing its host’s eggs and fledgling chicks out of the nest (contrary to existing belief that the adult cuckoo did it) was only confirmed in the 20th century, when photography became available. Having observed this behavior, Jenner demonstrated an anatomical adaptation for it—the baby cuckoo has a depression in its back, not present after 12 days of life, that enables it to cup eggs and other chicks and toss them out of the nest. The adult does not remain long enough in the area to perform this task. Jenner’s findings were published in Philosophical Transactions of the Royal Society in 1788.

“The singularity of its shape is well adapted to these purposes; for, different from other newly hatched birds, its back from the scapula downwards is very broad, with a considerable depression in the middle. This depression seems formed by nature for the design of giving a more secure lodgement to the egg of the Hedge-sparrow, or its young one, when the young Cuckoo is employed in removing either of them from the nest. When it is about twelve days old, this cavity is quite filled up, and then the back assumes the shape of nestling birds in general.”

Jenner married Catharine Kingscote (died 1815 from tuberculosis) in March 1788. He might have met her while he and other Fellows were experimenting with balloons. Jenner’s trial balloon descended into Kingscote Park, Gloucestershire, owned by Anthony Kingscote, one of whose daughters was Catharine.

Inoculation was already a standard practice, but involved serious risks. In 1721, Lady Mary Wortley Montagu had imported variolation to Britain after having observed it in Istanbul, where her husband was the British ambassador. Voltaire, writing of this, estimates that at this time 60% of the population caught smallpox and 20% of the population died of it. Voltaire also states that the Circassians used the inoculation from times immemorial, and the custom may have been borrowed by the Turks from the Circassians.

In 1765, John Fewster published a paper in the London Medical Society entitled “Cow pox and its ability to prevent smallpox”, but did not pursue the subject further. In the years following 1770, at least five investigators in England and Germany (Sevel, Jensen, Jesty 1774, Rendell, Plett 1791) successfully tested a cowpox vaccine in humans against smallpox. For example, Dorset farmer Benjamin Jesty successfully vaccinated and presumably induced immunity with cowpox in his wife and two children during a smallpox epidemic in 1774, but it was not until Jenner’s work some 20 years later that the procedure became widely understood. Indeed, Jenner may have been aware of Jesty’s procedures and success.

The initial source of infection was a disease of horses, called “the grease”, which was transferred to cattle by farm workers, transformed, and then manifested as cowpox. Noting the common observation that milkmaids were generally immune to smallpox, Jenner postulated that the pus in the blisters that milkmaids received from cowpox (a disease similar to smallpox, but much less virulent) protected them from smallpox.

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On 14 May 1796, Jenner tested his hypothesis by vaccinating James Phipps, an eight-year-old boy who was the son of Jenner’s gardener. He scraped pus from cowpox blisters on the hands of Sarah Nelmes, a milkmaid who had caught cowpox from a cow called Blossom, whose hide now hangs on the wall of the St George’s medical school library (now in Tooting). Phipps was the 17th case described in Jenner’s first paper on vaccination.

Jenner vaccinated Phipps in both arms that day, subsequently producing in Phipps a fever and some uneasiness, but no full-blown infection. Later, he injected Phipps with variolous material, the routine method of immunization at that time. No disease followed. The boy was later challenged with variolous material and again showed no sign of infection.

Donald Hopkins has written, “Jenner’s unique contribution was not that he inoculated a few persons with cowpox, but that he then proved [by subsequent challenges] that they were immune to smallpox. Moreover, he demonstrated that the protective cowpox pus could be effectively used for vaccination from person to person, not just directly from cattle. Jenner successfully tested his hypothesis on 23 additional subjects. Jenner’s fame, thus, lies in the rigor of his analysis and not in being the first to vaccinate. Ahhh !! How many “facts” did I learn in school that are wrong.

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Jenner continued his research and reported it to the Royal Society, which did not publish the initial paper. After revisions and further investigations, he published his findings on the 23 cases. Some of his conclusions were correct, some erroneous. The medical establishment, cautious then as now, deliberated at length over his findings before accepting them. Eventually, vaccination was accepted, and in 1840, the British government banned variolation and provided vaccination using cowpox free of charge. The success of his discovery soon spread around Europe and, for example, was used en masse in the Spanish Balmis Expedition, a three-year-long mission to the Americas, the Philippines, Macao, China, and Saint Helena Island led by Dr. Francisco Javier de Balmis with the aim of giving thousands the smallpox vaccine. The expedition was successful, and Jenner wrote, “I don’t imagine the annals of history furnish an example of philanthropy so noble, so extensive as this.”

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Jenner’s continuing work on vaccination prevented him from continuing his ordinary medical practice. He was supported by his colleagues and the King in petitioning Parliament, and was granted £10,000 in 1802 for his work on vaccination. In 1807, he was granted another £20,000 after the Royal College of Physicians had confirmed the widespread efficacy of vaccination.

In 1811, Jenner observed a significant number of cases of smallpox after vaccination. He found that in these cases the severity of the illness was notably diminished by previous vaccination. In 1821, he was appointed Physician Extraordinary to King George IV, a great national honor, and was also made Mayor of Berkeley and Justice of the Peace. He continued to investigate natural history, and in 1823, the last year of his life, he presented his “Observations on the Migration of Birds” to the Royal Society.

Jenner was found in a state of apoplexy on 25 January 1823, with his right side paralyzed. He never fully recovered and eventually died of an apparent stroke, his second, on 26 January 1823, aged 73. He was survived by one son and one daughter, his elder son having died of tuberculosis at the age of 21.

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In 1979, the World Health Organization declared smallpox an eradicated disease. This was the result of coordinated public health efforts by many people and organizations, but vaccination was an essential component. And although the disease was declared eradicated, some pus samples still remain in laboratories in Centers for Disease Control and Prevention in Atlanta, Georgia, in the United States, and in State Research Center of Virology and Biotechnology VECTOR in Koltsovo, Novosibirsk Oblast, Russia.

The eradication of smallpox was made possible by the fact that it must have a human vector to survive. No human carriers, no smallpox. I well remember getting vaccinated in 1965, then a requirement for all international travelers. I’ve still got the little telltale scar on my upper left arm – the stigmata of a generation. Then you needed a new vaccination every 5 years because cowpox vaccination is not 100% effective for life. I dutifully had mine but none ever took after the first.

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Jenner lived and worked in the dairy lands of Gloucester famous for cheeses. Before refrigeration, Gloucester milk spoiled before it could make it to London so it was converted to cheese. There are two types of Gloucester cheese – Single Gloucester and Double Gloucester – both made since the 16th century. Prior to that Gloucester cheeses were made from sheep’s milk. Gloucester is a traditional, semi-hard cheese, at one time made only with the milk of the once nearly extinct Gloucester breed cows (and now on the verge of disappearing again).

Double Gloucester, like Cheddar, is made all over the world and, as such, varies in quality and does not have protected status. Single Gloucester is made only in Gloucestershire and is protected. Both types have a natural rind (outer layer) and a hard texture, but Single Gloucester is more crumbly, lighter in texture and lower in fat. Double Gloucester is allowed to age for longer periods than Single, and it has a stronger and more savory flavor. It is also slightly firmer. The flower known as Lady’s Bedstraw (Galium verum), was responsible for the distinctively yellow color of Double Gloucester. In the United Kingdom today, of these two types of cheese, it is the Double Gloucester which is more likely to be sold in supermarkets. Both types are produced in round shapes, but Double Gloucester rounds are larger. Traditionally, whereas the Double Gloucester was a prized cheese comparable in quality to the best Cheddar or Cheshire, and was exported out of the county, Single Gloucester tended to be consumed within Gloucestershire.

Most Double Gloucester sold in UK supermarkets is slab cheese, made in large creameries operated by major dairy companies such as Dairy Crest. It is normally sold as a supermarket own brand. This version of the cheese is pasteurized but not processed.

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Gloucester cheeses are endangered again because of EU regulations (see http://www.dailymail.co.uk/news/article-2730022/Double-Gloucester-cheese-disappear-supermarket-shelves-cows-produce-dying-EU-regulations.html ). The EU forbids TB vaccination of dairy cattle because immunized cows test positive for TB and so cannot be distinguished from infected animals. A strange ironic twist given that this breed is the source of Jenner’s first smallpox vaccination. Breeders had built up herds in the 1970s but are reluctant to fight the regulations, so herds are again in decline. It is estimated that only 450 purebred cows exist today.

Good traditional Gloucester cheese is hard to beat eaten as is. But you can use it as you would cheddar in recipes. For me, give me some water biscuits, a nice pot of creamery butter, and a good wedge of Gloucester and I am a happy man.