Three hundred years ago, in 1721, England was in the grips of a smallpox epidemic.

"There were people dying all over the place," says Isobel Grundy, a professor emeritus of English at the University of Alberta in Canada. "Social life came to a standstill — and all the things we've suddenly become familiar with again."

But as Londoners cowered inside their homes, there was a woman who knew how to end the outbreak. Her name was Lady Mary Wortley Montagu, and she had learned a technique from women in the distant Ottoman Empire that could stop the pox in its tracks.

What happened next is a tale of politics and public health that bears some "depressingly similar" parallels to the current pandemic, Grundy says. But it also shows how science and determination turned the tide against one of the worst diseases humanity has ever endured.

Smallpox was far deadlier than the coronavirus the world is currently battling. Fatality rates were as high as 30%, and many of the dead were children. Those who survived were often left scarred by the disease, which covered the body in blisters.

But in the 1700s in the Ottoman Empire, centered around modern day Turkey, some women knew how to stop it.

These women were part of a vast informal network of female medical professionals. "There were a lot of women practitioners in the Ottoman Empire," says Akif Yerlioglu, a historian of Ottoman medicine at the University of Oslo in Norway. They were not allowed into the madrassas, Ottoman universities, but they shared knowledge among themselves, working as faith healers, midwives, surgeons and, even in one case Yerlioglu says, an eye doctor.

What these women knew was this: Take a bit of pus from a smallpox patient and use a needle to scratch a tiny amount just beneath the skin so it gets into the blood of a healthy person. That person would get a mild form of smallpox and become immune to the more serious version.

Yerlioglu says the practice is strikingly absent from Ottoman medical texts written by men, but accounts that do survive make clear that it was a well-known practice. "Women were sharing this knowledge, this know-how, among themselves," he says.

The technique was known as engrafting, variolation or, simply, inoculation. It is thought to have originated in China centuries earlier, and it was also practiced in India and Africa.

"We don't know exactly why or how it works, we just know that it does work," says Michael Kinch, an associate vice chancellor at Washington University in St. Louis who has written a book on vaccination. Kinch and others suspect this form of inoculation may have worked because it introduced the smallpox virus through the skin, rather than the lungs.

"By putting it in the place that is less deadly, i.e., the skin, then you would have a greater likelihood of surviving," he says. Another theory is that the inoculators were using a less dangerous strain of the virus.

This kind of inoculation did have risks. A relatively small number of people could become very sick and even die, and patients could give others smallpox. But it was far less dangerous than catching it through normal routes.

European doctors were aware of what the Ottomans and others were doing but they refused to believe it worked. At the time, "Europe was pretty isolated and it was fairly xenophobic," Kinch says.

Grundy says reluctance to adopt the practice was about prejudice, not science. "It comes from an Islamic country that we regard as backwards — 'How could they have the answer to smallpox?' — and also it was something done by women, which is bad."

This was where things stood when Lady Mary arrived in the Ottoman Empire's capital of Constantinople in 1717. Lady Mary was a wealthy noblewoman, married to the English ambassador to the empire. She was enthralled by the thriving metropolis.

"The art was completely different, the customs of life were completely different, the music, everything really," says Grundy, who has devoted much of her career to studying Lady Mary's writings. "So it was all very exciting to her, and among the new discoveries she took in was this practice of inoculating against smallpox."

Lady Mary described what she saw in a letter home to a friend. She told how old women kept pus from a smallpox victim in a nutshell and used a needle to create a tiny scratch in their patient's vein. She was instantly convinced of its potential.

"I am well satisfied of the safety of this experiment, since I intend to try it on my dear little son," she wrote. Lady Mary was ready to inoculate her son because smallpox had killed her brother a few years earlier, and shortly before traveling East, she had contracted it herself.

"She did survive but she was very, very badly marked. Her eyelashes never grew back after the smallpox and her skin was very much scarred," Grundy says.

She had her son inoculated in Constantinople. The family traveled back to England. And then, in 1721, came the major smallpox outbreak in London.

Lady Mary quickly arranged to have her daughter (also named Mary) inoculated. And as a member of the aristocracy, Lady Mary's decision got noticed. It was written about in the papers.

"By the time spots came up on little Mary, there was kind of a queue at the door to come and see her," Grundy says. "Both social acquaintances of Lady Mary and of high-placed doctors."

Lady Mary embraced the attention. In her letter of 1717, she had written of her desire to spread the practice of inoculation: "I am patriot enough to take the pains to bring this useful invention into fashion in England." But in the next breath, she expressed contempt for British doctors, who she believed were too preoccupied with making money: "I should not fail to write to some of our doctors very particularly about it, if I knew any one of them that I thought had virtue enough to destroy such a considerable branch of their revenue, for the good of mankind."

Rather than turn to the male medical establishment, Lady Mary sought to persuade the future queen of England, Caroline, the Princess of Wales, to inoculate her children. The princess, an ally of Lady Mary's, was willing to give it a try. After consulting with physicians and the king, the decision was made to conduct a series of tests "taking criminals condemned to death and asking them to volunteer to be inoculated experimentally," Grundy says.

Six condemned criminals were offered pardons in exchange for participating in the experiment. It was "by today's standards, wildly unethical," says Kinch. There were additional tests on orphans. These kinds of experiments were commonplace for medical professionals of the time — it was medicine as practiced in a society with a rigid class structure, where slavery was still legal.

"I think there was a different view of people's lives, and of the value of life and all lives being equal," he says.

In the end, the Princess of Wales did inoculate her daughters (her sons, possible heirs to the throne, were considered too important to risk), and Lady Mary became a public figure, which came with consequences.

The princess's decision made inoculation "a political matter," says Grundy. "Those who opposed the royal family would say, 'Oh, well this is something the Princess of Wales is doing, I wouldn't trust that.' "

There were others who mistrusted its Islamic origins and some who just resisted the idea of putting a foreign contaminant in their body. For Grundy, the cultural divisions Lady Mary encountered feel very familiar. She sees parallels in today's political fights over whether to wear masks, or the racially charged conspiracy theories claiming the coronavirus came from a Chinese lab.

"The repetition of the way in which battle lines get drawn, that's really extraordinary," Grundy says.

Kinch says Lady Mary's actions also offer lessons.

"One takeaway for everyone, whether it be scientists or nonscientists, is that we're not nearly as smart as we think we are," he says. "We have much we can learn from others."

Lady Mary wanted to stop smallpox, and to do it she was open to all ideas, he says. "Her brilliance and her open-mindedness helped her to embrace something that helped her to save hundreds of thousands, if not millions, of lives."

That's because the technique she'd borrowed from Ottoman women did take hold in England. Many thousands were inoculated, including a young boy named Edward Jenner. He went on to develop the first vaccine, also against smallpox. Vaccines proved to be safer and more effective than the old ways of inoculation. Smallpox was declared completely eradicated in 1980.

And vaccination is still being used today to fight new deadly viruses, including the coronavirus.

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