Vaccination: The Origin Story

We don’t often know how one discovery links to the next

Most everyone who knows anything about immunology has heard of Edward Jenner, the English country doctor credited with the discovery of vaccination in 1796. Jenner famously protected his patients against smallpox by injecting them with a gooey, milky pus taken directly from the infectious sites on the skin of milkmaids who were infected with the far less dangerous but related disease called cowpox.

In retrospect, the method seems to defy our sense of good hygiene, by a long shot. Jenner named his method ‘vaccination’, a word rooted in the Latin word for cow, vacca. His method is not something you imagine for yourself in a gleaming, modern hospital. It literally took pus from a festering wound on one person, put that into a syringe and injected it into another person. It seems disgusting, but it absolutely worked and saved hundreds of thousands of lives.

Vaccination nowadays never involves cows, but does often take a related generic approach, injecting a small amount of a weak virus into a person in order to prompt the immune system to raise antibodies against both that milder virus and also against any stronger version the patient might encounter. So, a weakened measles virus, when injected, can lead to protection against the real thing. That clear liquid in the syringe did not come from the arm of a milkmaid, of course.

I feel a kinship with Jenner for having injected weird things into a living creature with no certainty that it wouldn’t lead to certain death. I’d say Jenner’s efforts were weirder than the ones I did as a graduate student, since his took icky pus from sick people and injected it into apparently willing healthy ones. I at least had mostly purified my antibodies and then only tried them on obviously unwilling but nearly-blind, docile white mice.

While Jenner is quite famous, few people have ever heard of Lady Mary Wortley Montagu, who practiced what she called “variolation,” a version of this approach, 75 years before Jenner. Though her contribution is comparatively lost relative to Jenner’s, hers seems the more revolutionary, given that this method was new and unknown in England up to this point. Also, it’s worth noting, at the time, women were barred from formal medical education and from attending universities where higher-level scientific knowledge was taught. Lady Mary was largely self-taught, and obviously highly intelligent.

Image Credit: The Poetry of Lady Mary Wortley Montagu by Lady Mary Wortley Montagu

Lady Mary’s “variolation” method involved taking a tiny amount of pus from people who were infected with actual smallpox and then injecting that into healthy individuals. The difference from Jenner being that she didn’t have the insight or access to a weakened virus—she was using the real thing. When she was lucky, the amount she injected was what we would call sublethal, meaning it was still infectious, but the pus had so few viral particles in it that the immune system of the person being injected could start mounting an immune response before the virus could get ahead of it. The immune system thus got educated and the patient only got a little sick.

The key to her technique was keeping the dosage very low so that people didn’t immediately die from the infection, but not so low that the immune system didn’t notice. She did this extremely successfully with dozens of friends. But some of her subjects instead got full-blown smallpox and died, presumably because it was hard to standardize how much virus was in each batch of pus she harvested. In the early 1700s, knowing how much of the virus was safe to give was outside the bounds of established Western medical and scientific knowledge.

Lady Mary is rarely credited in the cute story of Jenner, the milkmaids and cowpox, which only rarely killed people in the course of trying to protect them. However, the history of Lady Mary’s variolation was no secret. Although variolation was scary (you could die), the idea of injecting pus had perhaps lost its barrier-to-entry problem by the time it occurred to Jenner. Although his recognition that cowpox was related to smallpox was insightful, it is not as weird to do what he did, if you knew first about what Lady Mary had done.

So where did Lady Mary get the confidence to consider injecting pus into her family and friends? Who does that? Like Jenner, she seemed to think outside of the box, a trait that is evident in her many letters.

But read her notes further and there is the glimmer, the ghost of an actual person who directly or indirectly showed her the way. His or her name is lost to history, but the passage of ideas is documented. Prior to developing her variolation method, Montagu had relocated for a period of years with her family to Constantinople (now Istanbul). During that time living abroad, she observed a local practice whereby they scratched the skin of children and introduced a small amount of pus from a mild smallpox case into the wound to induce immunity. Lady Mary herself had previously contracted smallpox, overcome it and developed immunity, but had been left visibly scarred for life. When she later returned to England, she had her young daughter publicly inoculated in London using the method she had witnessed abroad, both to protect her child and to demonstrate her trust in the technique.

This is often how discovery happens. Some courageous thinker(s) or some collection of “crazy” insights introduces a chain of new questions and ideas that eventually uncover new knowledge. In that process, we don’t know how many obstacles or gray areas we will encounter. Ideas fly amongst us, across distance and time, inviting new areas of inquiry for those curious enough to pursue them. Who originated the idea that a little bit of a bad thing (a virus living within pus) might protect you from a lot (full-blown illness, even death) is unknown, and so is how they first arrived at that idea. But what is clear is that this knowledge was passed along from node (individual) to another. For someone who is desperate, insightful or both, taking that step forward can set science in motion in a big way.