Doctor's Review: Medicine on the Move

October 21, 2021
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Safe Smallpox Inoculations

The search for safe smallpox inoculations ended in a barn

Dr Jekyll and Mr Hyde, the Fly, the Invisible Man -- some of fiction's biggest medical mistakes came from doctors experimenting on themselves. In real life, however, such experiments occasionally turned out for the best, even when the researchers in question committed an even bigger no-no. The first three Westerners to pioneer the practice of inoculation -- a wealthy lady, a dairy farmer and a country doctor -- all used their own kids as guinea pigs. Fortunately, no one was transformed into a murderous monster. In fact, the test subjects did something even more miraculous: they survived smallpox.

In the 18th century, there was plenty to be scared of, and smallpox ranked near the top of the list. The virus killed roughly 10 percent of Europe's population, with devastating outbreaks cropping up every few years. It was extremely contagious, spreading through airborne droplets and contaminated objects. The course of the disease was not pretty. After the initial flu-like symptoms, an eruption of pink spots would appear and soon develop into pustulant, oozing sores -- the notorious pocks. Mortality hovered between 20 and 40 percent. For those who survived, the pocks would dry up and flake off; for those who didn't, the end was painful and slow. Sometimes, subcutaneous bleeding turned the skin black and charred-looking, while organs began to hemorrhage uncontrollably. Despite the horror, death was often the preferred outcome, since survivors were left severely scarred, their faces nearly unrecognizable. Like lepers, they were shunned, ridiculed and pitied. Mercifully, many were left blinded as well, unaware of how frightening they appeared.

Lady Mary Wortley Montagu (1689-1762) was the first Westerner to use inoculation to fight smallpox. She was an unlikely pioneer in the field of microbiology, for not only was she a woman, but an aristocrat as well. Mary Pierrepont was born in London in 1689. Her father was the Duke of Kingston and she grew up in the typical manner of the British upper crust -- waited on hand and foot, with the best of everything a mere silver bell's ring away.

In 1712, she married Lord Edward Wortley Montagu. He was fairly progressive for his time, and didn't mind his wife's keen interest in the arts, history and science. Her widely published essays, poems and letters marked her as an early feminist and she became a popular fixture on the London literary scene. She was witty, wise and also very beautiful, so when the fabulous Lady Montagu was struck with the dreaded smallpox in 1715, it was particularly devastating. She survived to join her husband in Constantinople in 1717, a year after he was appointed English ambassador to the Ottoman Court. During the two years she lived there, Lady Montagu became mesmerized by the Turkish traditions and people, immersing herself in the culture, learning the language and writing about it all at a feverish pace.

While there, she noticed the crude and mysterious inoculations performed by the locals, who claimed that deliberately infecting healthy people with a weakened strain of smallpox rendered them immune to the illness later. The idea had apparently spread to Turkey from China. In ancient times, Chinese healers would collect fallen smallpox scabs, powder them and blow them up the noses of healthy people in an attempt to protect their patients from the dreaded disease.

Back in England, Lady Montagu shouted it from the rooftops: the Turks had found a way to beat the deadly smallpox virus! But, for a variety of reasons, nobody believed her. For one thing, she was a woman. On top of that, she'd been widely demonized in British society by her ex-friend, the poet Alexander Pope, after refusing his advances.

She decided to use her own son and daughter, aged five and four, to prove her point. Lady Montagu instructed her doctor to inoculate her children in a process she called "ingrafting" -- taking pus from the smallpox lesions of patients with a mild form of the disease and introducing it into light scratches in the skin, the way she'd seen it done in Turkey. As she'd expected, her kids became mildly ill and then recovered. People began to take notice.

When a bad outbreak hit London in 1721, the British royal family was worried. They'd heard of Lady Montagu's technique, but were hesitant to try it. Instead they decided to offer some prisoners the chance to win a royal pardon in exchange for their services as guinea pigs. Once the prisoners recovered from their inoculations, the royals were satisfied and the Princess of Wales inoculated two of her children. Within a few years, all of England was singing the praises of inoculation.

Although it certainly curbed the rate of smallpox transmission, it wasn't full-proof -- about three in 100 people actually died of smallpox as a result of the procedure and a great many others suffered for weeks before recovering, a hazard of using the live virus for inoculation. People sometimes even contracted secondary diseases from their pus donors, like tuberculosis and syphilis.

Lady Montagu is rarely remembered as the first to inoculate against smallpox. That distinction usually falls to the physician Edward Jenner. But there are also some historians who attribute the honour to a humble 18th-century dairy farmer. Benjamin Jesty (1737-1816) wasn't an aristocrat or a doctor. He knew little of science or society or even of smallpox. What he did know was cattle. On his farm in Dorset, a town in the English countryside, Jesty is said to have performed the first Western inoculation in 1774 -- almost 20 years before Jenner.

Worried that his pregnant wife or three young kids might contract the disease during the epidemic that raged that summer, Jesty put his mind to the problem. In accordance with the folk wisdom of the time, he knew he himself was immune, having survived the disease as a child. He also knew that his two dairymaids were immune (which they'd proven by caring for infected relatives) and that they'd only ever contracted cowpox, caught from lesions on the udders of infected cows. Jesty made the leap that deliberately infecting people with the more benign cowpox virus might also confer immunity to smallpox.

Using a knitting needle and pus from an infected cow, Jesty scratched up his family. They all contracted cowpox; his wife even ran a serious fever for a while, but they all recovered. Neighbours scoffed, but after the Jestys weathered the smallpox epidemic unharmed, people began asking him to inoculate their own families. Unfortunately, little paperwork exists to document Jesty's apparent success.

Edward Jenner's story, on the other hand, is well documented. When he was eight years old, Jenner (1749-1823) was inoculated against smallpox and apparently had a tough time of it, suffering in bed for weeks while the virus ravaged his system. Fortunately, he made a full recovery. Though he wasn't the first physician to inoculate his patients, he certainly found a better way to do it -- substituting the virulent smallpox virus for the cowpox one instead -- and almost single-handedly convinced the world it was the right thing to do.

As a country doctor working in Berkeley, he often treated cases of cowpox, and, like Jesty, knew that contracting it seemed to guarantee smallpox immunity. Legend has it he overheard a pretty milkmaid bragging about how "dabbling in the dew is what makes the milkmaids fair!" Inspired, he embarked on a series of experiments to see whether or not it was true. Some records suggest that Edward Jenner's first attempt at inoculation was actually in November of 1791, when he quietly inoculated his own 18-month-old son with cowpox.

However, it was on May 14, 1796, that Jenner famously and publicly used pus from a milkmaid's blister and scratched it into the skin of James Phipps, his gardener's eight-year-old son. The child recovered almost instantly and survived each of Jenner's numerous attempts to infect him with smallpox. And so the first smallpox vaccine was born. (The term vaccination, coined by Jenner, comes from vaca, the Latin word for cow).

Like Lady Montagu and Farmer Jesty, Jenner believed he had the answer to the smallpox problem. Unlike them, however, he had the credentials to back up his claim. He stood firm in his theory, which he presented to the Royal Society in London following his initial experiment. With his colleagues still unconvinced, Jenner repeated the trials on other children with equal success.

Despite being ridiculed, he devoted himself to proving that inoculation using the cowpox virus was far safer than using smallpox itself, staking his own money and reputation on it. Eventually, other doctors came around. In what may have been the first government grant for medical research, Jenner received an astonishing £30,000 (more than one million today) to continue his work. Within five years, people were being vaccinated throughout the Western world and smallpox would never again be feared in the same way.

Whether or not Edward Jenner knew of Farmer Jesty's nearly identical conclusions remains a matter of some conjecture. And his work should certainly be recognized as stemming from Lady Montagu's pioneering work nearly a century earlier. Still, Edward Jenner's accomplishments were hugely significant in the history of medicine. A modern scientist for his time, he insisted on using the burgeoning scientific method to determine whether or not inoculation was effective, instead of simply pushing forward with another untested "breakthrough."

Smallpox persisted until recently as a major killer, with an estimated 300- to 500-million victims throughout the 20th century. After a successful international vaccination program, the last known case of so-called "wild smallpox" was in 1977. One year later, Janet Parker, a medical photographer at the University of Birmingham in England, contracted the disease in a lab accident and died. Today, vaccination programs have ceased and the disease, at least officially, has been eradicated. But with fears of germ warfare on the public mind and unknown samples of the virus still possibly in existence, we may soon have to readdress the innovations of Lady Montagu, Benjamin Jesty and Edward Jenner.

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