Between Hope and Fear

by Michael Kinch

  Back in Gloucestershire, 1763 witnessed a perplexing mystery that would redeem England to some degree and counteract just a tad of the negative karma arising from Amherst’s fatal judgement. The enterprising John Fewster was attempting to variolate two brothers but was perplexed when they showed no signs of fever or infection. Thinking he had not performed the procedure correctly, Fewster subjected them to two additional variolation procedures, but none of the variolation procedures triggered redness, swelling or fever.13, 14 Upon questioning, the brothers responded that while neither had been previously infected with smallpox (which would be one explanation for why variolation had failed to trigger a response), both brothers had been infected earlier in life with cowpox.

  Still perplexed, Fewster reportedly returned home that evening and prepared for an evening of food, drinks, and discussion with colleagues at the Ship Inn near Alveston. The engagement was part of a monthly meeting of a group of physicians known as the Convivo-Medical Society. The party consisted of Fewster, Joseph Wallis, Daniel Ludlow, and Ludlow’s fourteen-year-old apprentice, a young man by the name of Edward Jenner.15 The Convivo-Medical Society meetings were partly professional, and, still perplexed, Fewster used the occasion to discuss the experience from earlier in the day with the two brothers, who’d failed to respond to variolation. The observation linking a failed attempt at variolation with cowpox apparently intrigued young Jenner, and through a remarkable coincidence, both would recollect the puzzling outcome at virtually the same time and place more than three decades later.

  Meanwhile eleven years passed and waves of smallpox came and went. In the summer of 1774, a key breakthrough came from an utterly unlikely source: a dairy farmer in Yetminter, in the southern England county of Dorset, approximately sixty-five miles south of Fewster’s hometown of Thornbury.16 The farmer, Mr. Benjamin Jesty, became alarmed at reports of smallpox in the region. Since time immemorial, dairy maids had been known for their complexion, as evidenced by sayings like “as smooth as a milkmaid’s skin.” To modern ears, milky skin is synonymous with an unblemished countenance, and advertisers have used this analogy to peddle many high-priced, milk-based cosmetics. Rather than referring to the properties of dairy products, a historical derivation of milky skin refers to the unblemished skin of milkmaids. Epitomes of beauty based on smooth skin were advanced by a variety of 16th-century Dutch artists, most famously Johannes Vermeer (such as in his 1658 oil on canvas portrait The Milkmaid). The concept of milkmaid as object of desire was also famously personified by Pilt Carin Ersdotter, an early-19th-century Swedish dairymaid. Pilt was so widely desired that she drew crowds of men to her stall in the central square market of Stortorget in central Stockholm.17 Her beauty was such that the commoner was propositioned by the Crown Prince and was later employed simply to sit in the parlors of the rich and famous. The maids featured in popular Dutch art and Swedish parlors were widely known for flawless skin that was unblemished, which meant that the skin was not covered in smallpox scars. A legend developed and spread implying that milkmaids were somehow exempt from infection with the pox and its disfiguring outcomes.

  Only they weren’t. While milkmaids did not usually suffer disfigurement or perish from smallpox (known today as variola major or minor), they were frequently infected with a relatively minor and more localized skin infection of the hand or lower arms, caused by a related pathogen known as cowpox (or vaccinia). Although unsightly during peak infection, cowpox spreads less and leaves little scarring, compared to smallpox.18 It was understood by dairy workers that cowpox readily spread from the udders of an infected cow to the maid’s hands and arms during the daily milking process. This usually occurred within months after a milkmaid had initiated her vocation, and the disease did not return thereafter.

  Benjamin Jesty, who was undoubtedly aware of this long-standing reputation, became intrigued by the fact that one of his dairymaids, named Anne Notley, seemed resistant to smallpox.19, 20 Anne was the caregiver for a family stricken with smallpox and had repeatedly been in contact with the sick but did not ever become ill herself. In talking with Anne, Jesty further realized that another of his employees, a milkmaid by the name of Mary Reade, had likewise nursed sick family members but did not show any signs of smallpox.

  With the return of smallpox in 1774, Jesty made the conscious decision to ignore variolation, which still held the prospect of extended isolation and severe, if not fatal, side effects. Instead, the farmer asked his friends and relatives if any cows in the region were currently displaying symptoms of cowpox.21, 22 None of Jesty’s own cows were infected at that time, so he walked from neighbor to neighbor, eventually locating a herd grazing miles away in Chetnole. This herd was experiencing an active infection with cowpox, and Jesty resolved to walk with his wife, Elizabeth, and two young sons, Robert (age two) and Benjamin (age three), to the herd and carry out an audacious act that would forever change humanity (an infant daughter, Elizabeth, was presumably deemed too young for such a daring experiment). Referring to the almost five-mile distance that Benjamin Jesty and his family had to travel, Patrick Pead wrote for the Lancet, “What happened in this meadow in 1774 was not the result of a simple farmer’s fleeting daydream—the act required inspiration, a firm resolve, and physical effort.”23

  What did happen was that Jesty, who had no prior medical training, borrowed one of his wife’s stocking needles and scraped some material from the udder of an infected cow.24 He intentionally infected his wife, just below the elbow, using a procedure remarkably similar to variolation. He then repeated the procedure with his two sons. Although there is no record as such, we can probably assume Jesty himself had been variolated and that he recalled enough detail from that procedure to replicate it on his family.

  Despite an ongoing smallpox epidemic in the area, none of the treated family members became infected. In the days after the procedure, Mrs. Jesty did suffer from inflammation, presumably arising from a procedure performed with dirty knitting needles surrounded by the muck of a Dorset cowshed. We know this because Jesty, who was not particularly interested in recognition for his bold experiment, was eventually required to take Elizabeth to the local doctor. The doctor chastised Jesty for his irresponsible actions, and Elizabeth recovered.

  In a series of events reminiscent of the initial public reaction to Cotton Mather’s experiments with variolation, word leaked out about Jesty’s experiment. The local community became outraged, though perhaps not for the reasons one might think. The crowd “feared their metamorphosis into horned beasts.”25 Jesty and his family were excoriated by his neighbors, who threw rocks (and various types of organic matter) at them when the Jesty family dared to show themselves outdoors. Perhaps for fear of the beasts lurking within, the family was forced to move far away, eventually isolating themselves on the Isle of Purbeck. The choice of this location was symbolically consistent with the fact that Purbeck, which is technically a peninsula and not an island, had housed the English king Edward the Martyr after his overthrow as king of the English centuries before.26

  Rather than becoming martyrs or transforming into minotaur-like creatures, Elizabeth and the children lived long and healthy lives, avoiding a later smallpox outbreak that devastated the region. We know this because Benjamin Jesty intentionally exposed his sons to smallpox a few years later. In 1789, fifteen years after being infected with cowpox, Jesty had his sons variolated.27, 28 Unlike a naïve patient, who would react with a localized and less virulent form of smallpox, neither of the two inoculated boys reacted to variolation—no local inflammation, no fever, and no signs of disease. Lacking a scientific background, Jesty might not have realized that the lack of infection by smallpox variolation meant that his earlier vaccination with cowpox had proven effective and was still working.

  While Jesty was pioneering cowpox vaccination in Britain, a parallel story was unfolding in the northern German state of Schleswig-Holstein, just outside Kiel. In this case, our protagonist was a peripatetic school tutor by the name of Peter Ple
tt.29 While teaching the children of a Mr. Weisse in the parish of Schonweide in mid-1790, Plett had what must have been quite an engaging conversation with Mr. Weisse’s mother-in-law. A former milkmaid herself, she relayed to Plett that she had been infected as a child with cowpox but was never bothered by smallpox. Like the story told to Jesty by his milkmaids, Mrs. Weisse related that she had remained healthy despite frequently serving as a caregiver to many others in the community suffering from the disease. Plett was intrigued and discussed this fact with other dairy maids, who confirmed similar experiences.

  Ever the itinerant teacher, he found himself a year later near Holstein (famous for their eponymous cattle). In the employ of a Mr. Martini in Hasleberg, Plett was tutoring two of Martini’s daughters, whose names were Hedwig and Margaret. By coincidence, a smallpox outbreak was raging in the area, and Martini’s daughters were gripped with terror that the disease would seek them out and disfigure their faces. The two girls learned of the connection between cowpox and smallpox (presumably based on a conversation with Plett). On their own initiative, the sisters went to a local dairy barn, sought out cows with active pox lesions, and rubbed the material over themselves. Despite the rather nauseating practice of covering their faces and hands in the revolting goop, the girls were disappointed to experience no eruption of cowpox pustules. Recalling his own experience with variolation, Plett eventually gave in to their pleading and performed a variolation-type technique on the girls with material oozing from cowpox sores. Specifically, the tutor introduced the infectious material just under the skin using his penknife to infect the hands of the two anxious sisters (as well as their younger brother, Charles). This action was taken without the foreknowledge of their parents. There does not seem to be any record of how the parents reacted to what certainly must have been a conspicuous infection between the thumb and index finger. What is clear is that Plett did not remain employed by Mr. Martini much longer. In 1794, the two coincidentally met in Kiel, where Martini conveyed his joy that while a particularly bad strain of smallpox had indeed infected the village, “the children he [Plett] had vaccinated had escaped all infection.” Working now in Kiel, Plett tried to convey his experiences to the faculty of the local university. However, the learned scholars brushed off any suggestions from a mere tutor, and variolation with smallpox remained the dominant countermeasure to manage the epidemic.

  Two years after the Kiel encounter between Plett and the grateful Martini, John Fewster, still practicing variolation, was dispatched to see the eldest son of a local and well-connected villager, John Player, who was suffering from early signs of smallpox. Here the details become rather fuzzy, primarily because they were related decades after the event. One version relates that a local polymath, John Player, had learned that Fewster successfully immunized multiple children in the village of Tockington with cowpox exudate and sought Fewster to vaccinate his son as a means to treat an active smallpox infection. Another version of the story suggests that Fewster had an epiphany during a conversation with Player while treating his son that night, which motivated Fewster to experiment with cowpox in place of variolation.30, 31 This second version states that Fewster then immunized three children. The motivations, machinations, and recollection of what occurred that night remain foggy but suggest Fewster took some time away from his “day-job” variolating to experiment during that spring of 1796. Fewster himself remains mostly silent on the subject, especially since the controversy was not aired until more than a decade after his death in 1824.

  In the same year Fewster was revisiting the concept of cowpox immunization, we return to the central figure of our story, Edward Jenner. Jenner’s contribution to vaccines began in 1796, forty-one years after Fewster’s puzzlement with the smallpox-resistant brothers (who had previously had cowpox), five years after Jesty, and coincident with Fewster’s renewed experimentation with cowpox. Despite not being the first to conceive of the idea, Jenner is rightly recognized as a key contributor to the adoption of vaccination by the medical community. His work is recognized largely because he was the first to invoke proper scientific method to evaluate multiple subjects and analyze the results prior to disseminating his work to the medical and scientific communities. In particular, Jenner’s work was cited and reviewed by the world’s most prestigious medical association of the time, the Royal Society of London.32

  As word of the discovery spread, Jenner was placed in positions of escalating responsibility to expand the adoption of smallpox vaccination. Given the increasing burden on his time, Jenner petitioned Parliament for a grant to pay for his services. While discussing how best to reward Jenner for services to his country, Parliament sought assistance from George Pearson, a prominent physician and advocate for vaccination.33 Pearson relayed rumors arising from southeast England that Jenner had not discovered the vaccine and that this was indeed the act of a previously unknown farmer from Dorset. These stories were largely set aside and Jenner received the bulk of credit from Parliament, along with grants of more than thirty thousand pounds sterling over the next ten years.

  Back in Dorset, Benjamin Jesty came to learn of the accolades being showered upon Jenner. Remembering the abuse that had triggered his family to flee their home in Yetminter, he was understandably loathe about bragging of his own experiments years before. Nonetheless, Jesty was encouraged to do so by his local rector, Andrew Bell, with whom he had privately shared his earlier experiment.34, 35 Jesty refused, so Bell began advocating for Jesty, approaching members of Parliament on his behalf. Ultimately, Bell and Pearson connected, and the two convened an 1805 meeting of the Vaccine Pock Institute, a government organization established to advance vaccination.

  Jesty was asked to appear before the Vaccine Pock Institute to describe his actions from thirty-one years before. Approaching seventy years of age, the farmer related his experiences and brought along his eldest son, Robert, as evidence.36 Robert volunteered to be variolated, which demonstrated continued immunity (though in practice, the fact that Robert had been variolated in 1789 overrode a conclusive demonstration that the 1774 vaccination had been efficacious). Based on this testimony, the committee agreed that Jesty had contributed to the discovery and should share in the recognition. While there is no evidence that Jesty was ever compensated financially (short of fifteen guineas to cover his expenses for his trip to London), the Jennerian Society recognized Jesty with a strongly worded statement affirming Jesty’s seminal contributions. They commissioned a portrait of the great man, who, ever the country farmer, posed in decades-old clothing and was loathe to sit still for the portraitist.37 Nonetheless, the recognition of Jesty’s contributions might have influenced the fact that when Edward Jenner was later elected to the prestigious Royal Society of London, it cited his groundbreaking work: the penning of The Natural History of the Cuckoo.

  Within a few years, the practice of vaccination with vaccinia (also known as cowpox virus) overtook variolation, due to its improved safety. By 1840, variolation was banned first in the United Kingdom and eventually across the globe. With the establishment of a safe and efficacious method for preventing smallpox, people developed an ambitious goal in the early years of the 19th century to fully eliminate the disease—an odyssey that would ultimately prevail after more than a century and a half of arduous work.

  Spreading Like a Virus

  A few clicks on your favorite search engine reveal that the term spreading like a virus is replacing the age-old saying spreading like wildfire. The author’s bias as a biologist supposes that the term virus usurped conflagrations as the object of choice based on recognition that respiratory diseases like the cold or influenza can disseminate quite rapidly (within days or weeks) throughout a community (a subject to which we will soon return). However, it must be conceded that millennials and other web citizens are undoubtedly more aware of, and actively concerned about, the digital form of viruses, whose propagation at the speed of light does admittedly outpace the velocity of a cough or sneeze.

  In the c
ase of the first vaccination, this new vernacular is both literally and figuratively accurate. As we have seen, Jenner’s discovery of using the cowpox virus for vaccination aroused considerable attention within the United Kingdom in the months following its revelation to the scientific and medical communities. The Jennerian approach with cowpox, unlike the experience of Benjamin Jesty years before, was fervently embraced as it provided an alternative to variolation. Recall that variolation utilized a highly pathogenic and readily transmissible infectious agent that was potentially life-threatening and highly inconvenient, as it required a monthlong quarantine and considerable support from caregivers. In contrast, vaccination in the truest sense of the word—with vaccinia virus—was generally safe. In the unlikely event that the infection was transmitted to another, this would simply serve to increase the coverage of individuals protected from smallpox. Within weeks, a government commission called the British Sick and Wounded Board mandated the vaccination of the Royal Navy and Army.38 Likewise, the civilian population of the United Kingdom largely embraced vaccination, and variolation was rendered obsolete, then barred within a few decades.

  Jenner himself devoted the rest of his life to spreading the word and teaching the practice of smallpox vaccination. To quote the man himself, “It now becomes too manifest to admit of controversy, that the annihilation of the Small Pox, the most dreadful scourge of the human species, must be the final result of this practice.”39 Jenner was handsomely rewarded by Parliament for his devotion, though the pillars of British government might not have been as enthusiastic had they realized some of the strategic implications of Jenner’s humanitarian views. Specifically, Jenner believed that the world should benefit from vaccination, and he readily communicated the details and shipped samples of cowpox (vaccinia) around the world.