How inoculation saved the world: A timely acknowledgment of the contribution of an English lady

Dr. Sandya Narayanswami is a life scientist with a B. Sc (Hons) in Biological Sciences from the University of Leicester, a PhD from the University of St. Andrews, Scotland, followed by postdoctoral training in the Chambon and Hamkalo Labs at the Universities of Strasbourg and California, Irvine. She combines faculty-level research experience at The Jackson Laboratory, Bar Harbor, Maine, with a 25-year track record of fundraising from foundations, corporations, and federal agencies, most recently at the California Institute of Technology. She launched her own consultancy in 2014 and got her pilot's license in 2019 through the Caltech Flying Club. She is currently Chairman of the Board of the General Aviation Awards, the US's oldest awards program in General Aviation, endorsed by the FAA. She has a profound passion for and understanding of science, together with a deep love and knowledge of literature and the humanities.

Research Highlights

• Lady Mary Wortley Montagu was the person who introduced inoculation for smallpox from Turkey to the Western world. Her work underlies all subsequent vaccination strategies, including that of Katalin Karikó, who shared the 2023 Nobel Prize in Medicine for her work on novel mRNA-based vaccines.
• Lady Mary's contribution is more relevant than ever yet it is routinely ignored, while Edward Jenner (1749−1823) gets all the credit. Jenner, however, did not introduce inoculation—he merely changed the antigen used to elicit an immune response from live smallpox to cowpox. While this made inoculation safer, it would not have been possible without an inoculation method.
• Willett's biography of Lady Mary is well-written and targeted to the general reader. It describes her efforts in terms that contemporaries today can relate to, for example, current rules for “clinical trials” and how data gathering was performed during the early stages of testing this new protocol.

With truly brilliant timing, just as the COVID pandemic accelerated in 2021, a new biography of Lady Mary Wortley Montagu (1689−1762),¹ a pioneer of inoculation as a medical technology, was published. Although nothing in the book specifically mentions the pandemic, the obvious message is that it is time to understand Lady Mary's contribution more broadly. Her work underlies all subsequent vaccination strategies, including that of another woman, Katalin Karikó, who shared the 2023 Nobel Prize in Medicine for her work on novel mRNA-based vaccines, which literally saved the world more than 300 years later.

Lady Mary, eldest daughter of Evelyn Pierrepont, first Duke of Kingston was the person who introduced inoculation or, as it was called, “engrafting” for smallpox from Turkey to the Western world. At the time, smallpox was causing waves of lethal epidemics throughout Europe. Lady Mary herself had caught the disease and survived although her brother William Earl of Kingston died from the infection in 1713.

Lady Mary married Edward Wortley Montagu, who in 1716 was appointed English Ambassador to the Sublime Porte (aka the Ottoman Empire). She, therefore, undertook with him the long journey from London to Constantinople, described vividly in her letters² and where she lived for several years. Highly intelligent and open-minded, she learned to speak Turkish and immersed herself in the culture of the Ottoman Empire. She introduced the comfortable and elegant Turkish women's costume, without corsets and with baggy trousers, to Europe, and made it the height of fashion. Unlike previous travelers from Europe, all male, however, she was uniquely placed to comment on what she observed, because as wife to the English Ambassador, she was able to visit the harems of the wives of the Ottoman courtiers. Here and in the women's bathhouses, which she describes vividly as the “Women's coffée-house”² where they exchanged news and gossip, she noticed that, unlike in Europe, nobody had any smallpox scarring.

Lady Mary soon discovered why. In her letter of April 1, 1717,² she describes “There is a set of old Women who make it their business to perform the operation. Every Autumn in the month of September, when the great Heat is abated, people send to one another to know if any of their family has a mind to have the small pox…..They make partys for this purpose, and when they are met (commonly 15 or 16 together), the old woman comes with a nutshell full of the matter of the best sort of small-pox and asks what veins you please to have open'd. She immediately rips open that you offer to her with a large needle…..and puts into the vein as much venom as can lye upon the head of her needle, and after binds up the little wound…and in this manner opens 4 or 5 veins..…. Then the fever begins to seize ‘em and they keep their beds 2 days, very seldom 3…and in 8 days time they are as well as before their illness.”² This ritual was usually performed in the women's quarters, by women, which is why it had not been observed by male travelers.

Lady Mary, a smallpox survivor living in a period characterized by successive increasingly virulent smallpox epidemics,¹ saw the potential of this procedure, which the Turks called “engrafting.” She had her son Edward inoculated in Turkey, and her daughter Mary, afterward Countess of Bute, inoculated in London. At the risk of her reputation, she promoted the procedure enthusiastically and persuaded Queen Caroline to have the royal children inoculated. This launched the gradual use of inoculation as an effective preventative of smallpox. The medical profession needless to say opposed it. They had no model for immunity and thus could not understand how giving a person a mild version of a disease could be protective.

What Lady Mary accomplished reverberates to this day and is more relevant than ever in this age of global pandemics. Yet, her contribution is routinely ignored, especially in the United States, while Edward Jenner (1749−1823) gets all the credit. Edward Jenner, however, did not introduce inoculation—he substituted inoculation with a less virulent cowpox virus for live smallpox virus, since immunity to one poxvirus conferred immunity to others. While this, by reducing the level of mortality to zero, made the method that Lady Mary introduced safer, it would not have been possible without having inoculation technology available as a basis for the experiment. As usual, Lady Mary's contribution, as happens too often to women's contributions to biomedical science, has long gone unnoticed and underappreciated.

Willett's biography of Lady Mary is well-written, well-researched, and targeted to the general reader. This is the need at the present time. Previous biographies³ emphasized her conflict with the writer Alexander Pope, her literary life, and self-imposed exile in Italy. With few exceptions,⁴ they largely failed to grasp the truly global impact of her introduction of inoculation. In contrast, Willett's biography describes her efforts in terms that contemporaries today can relate to. For example, the author discusses current rules for “clinical trials” when describing Lady Mary's inoculation of her daughter Mary in London, and how data gathering was performed during the early stages of testing this new protocol for disease prevention.

The author casts an interesting light on Lady Mary's dispute with Alexander Pope. You see how easy it was even then, let alone since #MeToo, for a man to destroy a woman's reputation. The result of this is that today, Lady Mary is merely a footnote in Pope Studies, and her contribution to medical technology, groundbreaking though it was, remains largely unnoticed, underappreciated, and undervalued. Lady Mary was also a famous feminist and wrote extensively on the disadvantages suffered by the women of her day. In Turkey, she had an extraordinary opportunity to compare cultures, and in her Letters,² her comments are scathing about Europe. Despite her social position, advantages, and toughness of character, she was taken advantage of several times by men. She knew what she was talking about when she railed against the inequities of marriage, and the limitations of women's lives. These limitations still extend to women's contributions to science and medicine. I could wish this biography had more detail on life in Turkey, but overall, I recommend it highly. It should be essential post-pandemic reading.