December 14, 2020

As vaccines start to be rolled out, the sceptics abound. Governments, pharmaceutical companies and the medical profession are distrusted by an often vocal minority. Yet, curiously, it was a very similar kind of distrust of authority that led to the spread of inoculation in the first place.

The story begins with smallpox, humanity’s deadliest ever enemy. It has claimed hundreds of millions of lives, having afflicted Eurasia and Africa since before the pyramids, and absolutely devastated the native populations of the Americas and Siberia when they came into contact with Europeans. In the 20th century alone, it killed an estimated 300 million people before its final eradication in 1979 — and those who were lucky enough to survive it were usually left permanently scarred. In many cases blind.

Yet for centuries, we also had a solution. Inoculation, or “variolation” (from the Latin for smallpox, variola) involved first collecting the fluid from the pustules of a smallpox victim, or crushing up the material from their scabs. The material was then either snorted as a powder, or rubbed into a scratch using a small knife — the lancet that gives its name to the now-famous medical journal.

The variolated person would still get smallpox, but their infection would usually be milder, and hopefully less deadly. It appears to have been used in India and China by the mid-16th century — it was in China where it was snorted — and in North Africa and the Ottoman Empire by the end of the 17th century, and even in parts of Wales since as early as 1600.

But it had not been adopted systematically. It was a sort of latent innovation, present among the folkloric, rural traditions of much of Eurasia and Africa, but often ignored by their official, urban medical professions. Part of the problem was that it was still dangerous. Variolation, unlike vaccination, still had some risk of death. It was generally practised as a last resort, to be used only in case of severe smallpox outbreaks. What would make Edward Jenner’s later discovery of vaccination so important was that he instead used the pus from non-lethal cowpox (variolae vaccinae), meaning that the word vaccination comes from the Latin for cow. Think vache in French, or vaca in Spanish.

Many of the 19th-century vaccinations should more accurately have been called equinations, as they often used horsepox instead, but when Louis Pasteur invented ways to immunise against anthrax and rabies, he named them vaccinations in honour of Jenner’s discovery. Vaccination was thus the name that stuck, and became more widely applied to methods of immunisation in general.

Of course, even non-lethal vaccines like Jenner’s, or those of Pfizer or Moderna today, face their challenges in gaining social acceptance and trust, despite all the evidence in their favour and the significantly more careful and rigorous testing (Jenner began by simply vaccinating his gardener’s son, and then tried to infect him with smallpox. He survived, luckily). Just as the MMR vaccine was infamously blamed for autism, even some doctors in the late 19th and early 20th centuries blamed smallpox vaccines for causing leprosy, cancers and miscarriages. But for still-lethal variolation, the climb to social acceptance was even steeper.

Enter Lady Mary Pierrepont, woman of letters, celebrated poet, anonymous journalist and aristocrat, whose elopement in 1712 may have been the most important marriage in human history. For her new husband, Edward Wortley Montagu, soon became the ambassador to the Sublime Porte of Constantinople, taking her and their young son with them.

It was in the Balkans, Greece and Turkey, that Lady Mary observed the practice of inoculation, and having once experienced the horrors of smallpox herself, had her son inoculated there. Her son, incidentally, would later become an adventurer extraordinaire, running up debts across Europe, getting involved with highwaymen, running a gambling extortion racket, probably doing some spying both for and against France, distinguishing himself in a major battle, helping negotiate the end of the War of Austrian Succession, converting to Islam, becoming an influential scholar of Middle Eastern customs and languages, committing bigamy twice — even tricking his third wife into committing accidental bigamy herself, by convincing her that her actual husband had died — and, of course, being elected an MP.

In Turkey, Lady Mary decided that she would make it her patriotic mission “to bring this useful invention into fashion in England”. She was not the first westerner to have a child inoculated in Turkey, nor was she the first person to send word of the procedure back to Britain. The country’s premier scientific organisation — the Royal Society — had received word of the practice a few years before her trip.

But when an especially bad smallpox epidemic swept into Britain in 1721, Lady Mary was the one who introduced inoculation into wider practice. She arranged for her daughter to be inoculated in England by the surgeon who had accompanied her husband’s embassy, Charles Maitland — who, significantly, insisted that it be done in the presence of a few medical experts.

Needless to say, the daughter thrived — indeed, she would grow up to be the wife of a prime minister, the Earl of Bute. But the hallmark of early 18th-century science was a healthy dose of distrust; one successful case and a few reports of inoculation abroad was not enough. The Royal Society had been founded a few decades earlier on the basis that all prior knowledge should be put to the test, and the old authorities rigorously interrogated. It was not enough to take Aristotle’s word for things, and certainly not Turkish folklore. Nullius in verba, went the society’s motto: take nobody’s word for it. Knowledge thus had to be confirmed by experiment, in the presence of witnesses, before it could be granted the authority of “fact”.

Using her court connections, Lady Mary interested Princess Caroline, the wife of the heir to the throne, who arranged for an experiment to be performed on prisoners in Newgate gaol. Six people destined for the gallows were offered their lives and a pardon in exchange for undergoing inoculation — all six survived, with one of them turning out to already be immune, and the other five experiencing only a mild form of the disease.

It was promising initial evidence, and inspired local doctors around the country to begin inoculating their patients. Meanwhile, an American clergyman named Cotton Mather arranged for hundreds of inoculations as smallpox swept Boston. So the Royal Society began to gradually build a more convincing set of statistics on inoculation’s effectiveness, which yielded clear results: albeit still potentially fatal, the risk of death was very much lower than from contracting the disease normally. Initially about one in fifty, compared to one in six.

It still took decades for inoculation to become acceptable. Mather’s home was attacked with a grenade, and Lady Mary Wortley Montagu had abuse hurled at her in the newspapers and in the streets. Her own distrust of authority — she suspected that doctors might oppose inoculation on the grounds that it would “destroy such a considerable branch of their revenue” — may also have got in the way of her mission. In print, she criticised the way English physicians conducted the operation. But on the whole, she succeeded. In 1722, Princess Caroline became fully convinced and had the royal princes and princesses inoculated, with many aristocrats following suit.

George I even wrote to a daughter back in Germany, to try and persuade her to inoculate the future Frederick the Great of Prussia. And the growing statistical evidence collected by the Royal Society helped gradually confirm the belief in inoculation’s relative safety, converting it into established fact. It was thanks to the scientist’s inherent scepticism, tempered by the search for better evidence, that inoculation gained approval, became more common, was later improved in its safety, and ultimately led to the invention of non-lethal vaccinations. Hundreds of millions of lives have been saved as a result.