Historical Perspective: Conflicts Over Immunization Prior to the Age of Vaccines

David M. Warmflash, MD


December 22, 2022

An ounce of prevention is worth a pound of cure.

Printing this now-popular expression on February 4, 1735 in The Pennsylvania Gazette, Benjamin Franklin was referring to the prevention of town fires. He didn't mean fires from lightning strikes — his lightning-rod invention still lay 17 years into the future — nor was he alluding specifically to the prevention of disease. But he might as easily have mentioned disease, had he coined the phrase 2 years later. On November 21, 1736, Franklin would lose his 4-year-old son to smallpox and, still more tragically, he would soon realize that he actually could have prevented it.

To be sure, the British physician Edward Jenner would not invent vaccination until the year 1796. But, as an 8-year-old in Gloucester, England, in 1757, Jenner himself was immunized against smallpox by an older, cruder method: inoculation, also called variolation, which is where the smallpox virus, Variola, derives its name.

Whereas Jenner's innovation was to expose people to pus from lesions of cowpox, leading his friend and colleague Richard Denning to call the practice vaccination (derived from vacca, Latin for cow), inoculation utilized lesions on actual smallpox victims. Pus was taken from smallpox lesions and scraped into the skin with a lancet, or dried smallpox scabs were put into a tube and blown into the noses of people to immunize them. Either way, the strategy was to inoculate people with the then-unknown causative agent, producing what hopefully would be a mild case of smallpox.

The scope of vaccination ultimately would be expanded by Louis Pasteur and then others to encompass any technique to achieve active immunization without inoculation (administration of the unaltered disease-causing agent itself). But prior to Jenner, inoculation was the best option against smallpox, even though 1%-2% of variolated people developed fatal cases of smallpox. That sounds scary until you learn that the case fatality rate of smallpox in unimmunized people was typically 30%. Thus, prior to Jenner, the risk-benefit favored inoculation, including in 1730s Philadelphia, where Franklin did know about the practice.

Indeed, Franklin, 31-years-old at the time, still probably knew more than most other Philadelphians about inoculation because of the place where he had grown up: Boston. So let's take our medical time machine to that city, specifically to the year 1721, when a 15-year-old Franklin was apprenticed in his brother's print shop, each day walking the same narrow curvy streets as another Bostonian, the clergyman Cotton Mather.

Grab some 18th-century New England attire. Dust off that tricorn hat, but also, let's get some smallpox vaccine scarified into our arms, even those of us who are old enough to have had that done with bifurcated needles as babies because it's not clear how strong any remaining immunity is. We'd better get immunized against typhoid fever and cholera, too, so pack some gentamicin, doxycycline, or a fluoroquinolone — just in case of bubonic plague. And let's remember malaria prophylaxis. Amazingly, the Anopheles mosquito did reach Massachusetts in early American history.

The name Cotton Mather may evoke memories of being bored in your 11th grade history class when learning about the speeches that this Puritan minister made, but his story gets interesting when smallpox hit the Massachusetts colony. That's because of something that Mather learned from Onesimus, an enslaved man who worked in Mather's home who hailed from West Africa, where the practice of smallpox inoculation was in effect. In part with the statistics on smallpox mortality that we noted above, Mather reasoned that it was probably a good idea to get as many Bostonians inoculated as possible before the expanding smallpox outbreak of 1721 reached a peak.

All Mather needed to get started were some doctors because that's who knew how to use a lancet (mostly for bloodletting), plus it wouldn't hurt to have someone with medical credentials onboard. Though many physicians scoffed at the idea, Mather won over a physician named Zabdiel Boylston, who proceeded to inoculate those who were willing. Zabdiel Boylston was an ancestor of Ward Nicholas Boylston, for whom Boston's Boylston Street is named and whose cousin, Susanna Boylston, would become the mother of John Adams and mother-in-law to Adams' wife, Abigail.

It's reasonable to think that this particular Massachusettsan history and its connect to the Adams family played a major role in this first couple themselves getting inoculated — John during an outbreak in 1764 and Abigail in 1776, along with all of their children — and becoming advocates of the practice alongside Franklin, who was actively promoting inoculation in Philadelphia and had been doing so for decades.

But just like the eventual resistance to vaccination, inoculation had its opponents, even when Matter and Boylston first tried it in 1721. In the medical community, providing the opposition with an image of authority was a prominent physician, William Douglass. Though Douglass did not dismiss arguments by others that such intervention conflicted with divine will and things like that, his main problem with inoculation was that it was untested — which was true, although virtually everything that doctors did back then was untested compared with how we test treatments today scientifically — and that it derived from folklore. This idea could have related to the origins of inoculation in the Eastern, non-European world. Along with Africa, this included the Ottoman Empire and other places that may have evoked intrigue but also suspicion among Westerners. Objections like those of Douglass were not the limit of the resistance either, for there was also violence, manifesting when one opponent of inoculation threw a bomb through the window of Mather's church.

Fortunately, the bomb did not explode, and during the summer of 1721, Boylston inoculated some 287 Bostonians, of whom, 2% were recorded to have died compared with 14.8% of those suffering from natural infection. It's not clear whether the teenage Franklin was among this group of inoculees, but it's possible that some other physicians joined Boylston's efforts at some point, expanding the numbers. Meanwhile, though, with physicians of the likes of Douglass in opposition, and similar opposition emerging across the ocean in England, the stage was set for opposition to continue into the vaccination era on both sides of the Atlantic, beginning with opposition to Jenner himself.

On the Massachusetts side, around the year 1800, Benjamin Waterhouse, a Harvard physics professor, played a role similar to the one that Mather did eight decades earlier: He introduced the new practice to the United States. Like Jenner, Waterhouse could not explain how vaccination worked nor could any physicians who administered it. Nothing close to that knowledge would come, until the 1880s, when Louis Pasteur would begin to figure it out, developing new vaccines in the process. (Pasteur, Robert Koch, and how their work and rivalry led to the first vaccines targeted specifically to particular diseases warrants its own article, so stay tuned)

Meanwhile, in Europe and America, many decades would pass before people, also largely on account of Pasteur, would learn about infection and contamination. Dependent on cowpox lesions as the source, vaccination was not always available throughout much of the 19th century, so doctors continued with inoculation. Many of them mixed and matched, sometimes inoculating and sometimes vaccinating. Naturally, they often used the same lancet for both practices, meaning that there were instances in which people were getting vaccinated but at the same time getting inoculated. So we shouldn't be surprised that there were instances of vaccination producing mortality rates equaling those of inoculation.

Of course, this danger gave early antivaccine activists more reason to be concerned; but their influence was already strong because their movement, in a very real sense, predated vaccination itself. As for what motivates vaccine opponents today, this is a complex topic, but within the scope of today's story, I can't help but wonder if one component of the problem is that many 21st-century people think that vaccines — whether mRNA, viral vector, subunits, inactivated whole virion, or live attenuated — are actually inoculants of whatever disease each is supposed to prevent. It probably doesn't help that many journalists like to use the terms vaccination and inoculation synonymously. Let's ask them to stop doing that.

Whatever has motivated vaccine opponents through the centuries, their ranks have always been destined to include people who would make the ultimate miscalculation of not vaccinating a child against a deadly disease and then seeing that child die as a result of the mistake — people who, in later centuries, would experience the same kind of horror as Benjamin Franklin had experienced in 1736.

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