Maybe you know that Edward Jenner is sometimes called the “Father of Immunology.” Maybe you know that Jonas Salk developed the polio vaccine and declined to patent his invention. Maybe you’ve kept your finger on the pulse of vaccine news in the wake of the COVID-19 pandemic and consider yourself something of an amateur expert on the topic.
Whatever level of knowledge you have, there’s always more to learn about vaccines, from when they were introduced to how they actually work. Was Catherine the Great an early proponent or opponent of the smallpox vaccine? Why did we start calling it a vaccine in the first place? Learn all that and more in this list, adapted from an episode of The List Show on YouTube.
1. Lady Mary Wortley Montagu witnessed inoculation in Constantinople.
British physician Edward Jenner is usually thought of as the father of vaccination, but did you know that someone else introduced inoculation to England several decades earlier? In other parts of the world, in fact, the practice had been happening for centuries.
Lady Mary Wortley Montagu, born in 1689, was a poet and essayist married to the British ambassador to the Ottoman Empire. When she was 26, a bout with smallpox left her with facial scars. She and her husband moved to Constantinople—modern-day Istanbul, Turkey—in 1716. Lady Mary explored the city’s women-only apartments and public baths, where she witnessed Ottoman women inoculating people against “distemper.”
In a letter, she described the women applying “the matter of the best sort of small-pox” to small cuts in patients’ arms or legs, after which they would suffer a very mild case of the disease and then recover. No one ever died, she wrote, and following the procedure they were immune to the illness.
Montagu was so convinced of the practice’s safety that she intended to introduce it to the British medical establishment. In 1721, a smallpox outbreak in London prompted her to have her daughter inoculated—the first known instance of the procedure in England. But many doctors remained skeptical. That August, an experiment that would never be approved today was conducted at Newgate Prison: A group of inmates was given the option of freedom if they submitted to inoculation and lived. They all survived. After that, the Princess of Wales inoculated some of her children—again, they were fine—and the procedure became widespread.
2. Royals were some of the first Europeans to try inoculation.
The princess wasn’t the only European royal worried about viruses. Russia’s Catherine the Great summoned an English doctor, Thomas Dimsdale, to Saint Petersburg in 1768 to administer a smallpox inoculation to herself and her son, Grand Duke Paul. The operations had high stakes: While Dimsdale prepared the injection, there were said to be a number of carriages at the ready in case something went wrong and the doctor needed to escape an angry mob of the empress’s followers. Fortunately, the top-secret procedure went off without a hitch.
3. A number of cultures beat Europeans to inoculation.
The same year as the Newgate prison experiment, the Massachusetts Bay Colony was suffering from its own smallpox outbreak. Years earlier, the colony had tried to keep disease at bay by initiating the first quarantine in the North American colonies. Governor John Winthrop ordered all ships arriving from the Caribbean, where yellow fever was widespread, to remain offshore until cases of “ye plague or like in[fectious] diseases” were resolved.
Epidemics still struck the colony fairly regularly. It would take a while for inoculation to be adopted on this side of the Atlantic, but information supporting the practice already existed in a number of cultures.
By the early 1700s, forms of inoculation had been practiced in India and China for more than a century. The written record is a bit spare, with explicit references dating only to around the mid-1500s. Some experts believe the practice significantly predates that record, though—the information may have been passed down as part of an oral tradition.
By 1714, not long before Lady Mary Montagu arrived in the Ottoman Empire, a physician named Emmanuel Timonious wrote about how inoculation was becoming increasingly prevalent in Constantinople in a letter printed in Philosophical Transaction.
4. An enslaved man named Onesimus informed Cotton Mather about inoculation.
Two years later, Puritan minister Cotton Mather—best known for his role in the Salem Witch Trials—wrote his own letter supporting Timonious’s account. Mather probably hadn’t witnessed inoculation at this point, but he had secondhand knowledge of the practice from an enslaved man who worked for him. Mather described an incident in which he asked the man, whom he called Onesimus, if he had ever had smallpox. Onesimus “answered, both yes and no,” and described how people in his homeland applied infectious pus to patients’ scratched arms, rendering them immune to the disease.
Again, the written record makes it hard to trace this tradition. For what it’s worth, a late 18th-century French writer later claimed that many West Africans had been conducting inoculation since “time immemorial.”
5. Cotton Mather faced heated pushback against his public health efforts.
When Boston was hit by a smallpox epidemic in 1721, Mather urged doctors to use inoculation in their fight against the disease. As in England, many were skeptical. Some argued that inoculation went against God’s commandments. Someone even threw a grenade through Mather’s window with a note that read, “COTTON MATHER, You Dog, Dam you. I’ll inoculate you with this, with a Pox to you!”
6. Zabdiel Boylston attempted to quantify the benefits of inoculation.
One doctor, Zabdiel Boylston, did inoculate nearly 300 patients. The process was far from perfect—roughly 2 percent of those patients died. But compared to smallpox’s fatality rate of about 15 to 30 percent, Boylston’s meticulous records demonstrated to many that inoculation had the potential to save lots of lives.
7. Benjamin Franklin lost his unvaccinated son to smallpox.
Inoculation—or the lack thereof—played a role in the lives of America’s founders. Benjamin Franklin became a strong proponent of the medical intervention after losing his 4-year-old son, Francis, to smallpox in November 1736.
Some in Philadelphia began a rumor that the boy was inoculated but had died anyway. Franklin set the record straight, and later wrote in his autobiography, “I long regretted bitterly and still regret that I had not given it to him by inoculation. This I mention for the sake of parents, who omit that operation on the supposition that they should never forgive themselves if a child died under it; my example showing that the regret may be the same either way, and that therefore the safer should be chosen.”
8. John Adams had a tough time with his generation’s version of inoculation.
In 1764, John Adams was inoculated in Boston during yet another smallpox outbreak there. At the time, doctors accompanied the procedure with an unnecessary regimen of purging and sweating (via large doses of mercury and, oddly enough, milk). Adams wrote in his autobiography that the treatment caused him to drool so much that every tooth in his head loosened: “By such means they conquered the smallpox, which I had very lightly, but they rendered me incapable ... of speaking or eating in my old age, in short … the same situation with my friend Washington.”
9. George Washington mandated inoculation for the Continental Army.
In 1776, half of the 10,000 Continental Army soldiers in Quebec, including their commander, came down with smallpox. The unit retreated, leaving the territory in British hands (and arguably leading to Canada’s status as a separate country today). The defeat may have convinced Washington to mandate inoculation for the army in 1777.
10. Edward Jenner used one virus to protect against another.
Inoculation did have a few drawbacks. One was that newly inoculated patients could pass on the disease as they recovered from their mild case. And there was no standardized dosage to ensure that the case would, in fact, be mild. It was better than nothing, but left a lot to be desired. Then, Edward Jenner came along.
Jenner’s big breakthrough came from looking into how exposure to a less-deadly yet related virus conferred immunity to a deadlier one. In 1796, he treated a milkmaid named Sarah Nelmes for a cowpox infection, which she said she got from her cow, Blossom. In his famous experiment, he took pus from Nelmes’s sores and inoculated an 8-year-old boy named James Phipps with it. Phipps recovered, and Jenner inoculated the kid with smallpox material. Phipps did not get sick. The procedure in which a weaker or dead virus confers immunity became known as vaccination, after the Latin word vacca, meaning cow.
11. Inoculation and vaccination aren’t technically synonymous.
In Jenner’s day, at least, inoculation referred to the act of applying infectious material to a skin lesion, while vaccination referred specifically to applying less-dangerous cowpox material to avert smallpox. Today, the two terms are often used interchangeably to refer to any practice in which something is introduced to the body to help the immune system protect against disease.
12. Cows’ connection to vaccination led to some outlandish ideas.
Back in the 18th century, the bovine connection gave some people the wrong idea. Many were suspicious of a medical treatment derived from a cow, not to mention the concept of purposefully getting one disease to prevent another. Some claimed that mingling animal and human substances went against Biblical tenets.
A famous historical anti-vaxxer named Benjamin Moseley even warned people that vaccinated might lead to “quadrupedan sympathy.” In other words (at least half-seriously, it seems), Moseley thought an unlucky vaccinated person might become attracted to cows. Illustrator James Gillray captured the hysteria with a cartoon depicting miniature cows morphing out of people’s bodies (above).
13. Blossom likely survived her brush with medical history.
Of course, none of those dire predictions came true. But what happened to Blossom, the only actual cow involved in the story? She likely recovered from the cowpox infection, since its lesions tend to heal within a month or so. Today, her hide is preserved and mounted at St. George’s Medical School in London [PDF], and one of her horns is part of the collection at Dr. Jenner’s House, Museum, and Garden in Gloucestershire, England.
14. Spain used orphans to harvest viral material for vaccines.
One problem with vaccinations was that scientists couldn’t yet manufacture a vaccine. The viral material had to come from an already-infected person, which made public health vaccination campaigns difficult. But in 1803, the Spanish government found an unconventional, and highly unethical, workaround.
King Carlos IV wanted to vaccinate people in Spain’s American and Philippine colonies. Physicians came up with a plan involving a ship, a crew, and 22 orphaned children. The idea was to set sail and then vaccinate the children in succession, with one child providing the cowpox pus to the next one, and so on, forming a human chain and ensuring access to the valuable viral material. While the kids were eventually settled in Mexico, the captain of the voyage, Francisco Xavier de Balmis, continued his round-the-world vaccination mission for the next four years.
15. Vaccines were the first instance of free medical service in the UK.
Vaccination became the gold standard in medicine because it was so much safer than inoculation. In fact, the UK banned variolation—another name for inoculation with the smallpox virus—in 1840 with the passage of the national Vaccination Act. This law also provided free vaccines for the poor, the first instance of free medical services in the UK. Vaccination for newborns became mandatory there in 1853, and in 1855, Massachusetts passed the first state law in the U.S. requiring them for school children.
16. Special farms arose to meet vaccine demands.
With the need for vaccine doses growing every year, scientists devised a method for propagating cowpox among calves for use in vaccines, a product they called “animal vaccine.” Basically, scientists harvested infectious fluid from the cows for use in smallpox vaccines. This was safer than transferring pus from one person to another, because it cut down on the risk of transmitting other diseases, such as syphilis.
After a Boston physician introduced the concept to U.S. researchers, entrepreneurs quickly opened “vaccine farms” to increase production. The New York City Board of Health opened a vaccine farm in Clifton, New Jersey, in 1876 to raise cows infected with cowpox. By 1897, more than 14 major vaccine farms were in operation across at least six states. Dryvax, a smallpox vaccine manufactured by Wythe Laboratories and used for most of the 20th century in vaccination campaigns, was derived from a strain harvested at the New York Board of Health vaccine farm.
17. Louis Pasteur used attenuated anthrax to develop a vaccine.
Smallpox received a lot of attention because it was so deadly. But it wasn’t the only viral disease for which scientists raced to create vaccines. French chemist Louis Pasteur discovered that bacteria lost their virulence over time, a process he called attenuation. In a landmark 1881 experiment, he vaccinated a group of livestock twice with attenuated anthrax vaccine and left a control group unvaccinated. About two weeks later, he exposed all of the animals to live anthrax. Within a few days, the unvaccinated sheep and goats had died while the vaccinated ones remained healthy.
18. Pasteur also developed a vaccine for rabies.
Pasteur tried a similar tactic with the lethal rabies virus. He and a colleague extracted tissue from rabid dogs and injected a solution of it into a series of rabbits, where the virus weakened. Pasteur air-dried the rabbits’ spinal cords—exposure to oxygen reduced the virus until it was no longer infectious—and then administered the material to 50 more dogs, who remained healthy.
Seems like a success, right? Two problems: Pasteur was not a medical doctor, and he definitely did not have a license to test his vaccine in humans. But that’s exactly what he did when the mother of 9-year-old Joseph Meister brought the boy, who had been bitten by a rabid dog, to Pasteur’s laboratory. Over the course of 11 days, Meister received 13 shots and survived. As an adult, Meister worked as a caretaker at the Institut Pasteur in Paris.
19. The story of Salk’s altruism may be an oversimplification.
There’s a long-standing legend attached to the development of the polio vaccine in the early 1950s. Numerous researchers were working on polio vaccines at the time, using forms of a live polio virus. Jonas Salk, a virologist at the University of Pittsburgh with funding from the National Foundation for Infantile Paralysis, developed a vaccine using an inactivated virus, which was administered by injection. He took what seemed like risky steps—he tested the vaccine by inoculating his family, and then launched a clinical trial of more than a million children aged between 6 and 9. But the trial showed the vaccine prevented infection.
Salk did not patent the vaccine, allegedly because he wanted it given to children far and wide regardless of cost. “Could you patent the sun?” he asked in a televised conversation with Edward R. Murrow in 1955. People took it as a moral statement against patenting medical breakthroughs, but the reality is a bit more complicated.
Salk’s polio vaccine was the culmination of a massive effort by public and private entities. The year it was unveiled, according to Claire Gaudiania’s The Greater Good, 80 million people donated money to the National Foundation for Infantile Paralysis. As Brian Palmer argued in a piece for Slate, in this particular case, patenting and profiting off a vaccine that had been developed with so many donations would have been seen as “double charging.” (In fact, many of those donations were small sums from the not-particularly-well-off, helping give rise to the Foundation’s current name, the March of Dimes.)
Salk’s public profile as a savior of children led TV viewers to assume his poetic rhetorical question was meant to apply to all vaccines, in a purely altruistic vein, but it may well have been more contingent on the details of his particular vaccine and its origins.
Viewers also didn’t know that the National Foundation for Infantile Paralysis had actually looked into patenting the technology. Its lawyers concluded that the vaccine wouldn’t be patentable because of “prior art”—in other words, because other researchers had been working on polio vaccines and Salk had built on their research, his invention wasn’t unique.
It’s not clear that the Foundation ever intended to profit on this hypothetical patent—it might have just been a way of preventing other companies from making low-quality knockoffs of the vaccine—but it does, perhaps, undercut some of the nobility of Salk’s lofty question.
20. Albert Sabin collaborated with Soviet scientists on vaccination programs.
Albert Sabin later developed a polio vaccine using the live polio virus that could be administered orally, which made distribution much easier. And at the height of the Cold War, Sabin and his Soviet counterpart, Mikhail P. Chumakov, collaborated on a vaccination campaign in the U.S.S.R. In 1959, 10 million Soviet children received Sabin’s oral vaccine. In 1960, 100 million people behind the Iron Curtain were vaccinated. In another instance of “vaccine diplomacy,” the U.S.S.R., with U.S. funding, provided millions of doses of a freeze-dried smallpox vaccine to developing countries.
21. mRNA vaccines represent a somewhat new—but not untested—medical breakthrough.
The Pfizer and Moderna COVID-19 vaccines are mRNA vaccines, and while it might seem that this technology just emerged from nowhere, scientists have been working on the core ideas for decades and had even tested mRNA vaccines before the current pandemic.
mRNA vaccines don’t contain any of the coronavirus, live or dead. Instead, when you receive your shot, molecules called “messenger RNA” tell your cells to start creating a “spike protein” that’s found on the coronavirus itself. Then, your immune system makes antibodies against that protein.
You already have mRNA in every cell of your body—it’s the protein that transports messages from your DNA to the rest of your cells. The mRNA vaccines use the same kind of molecule to tell your cells to make a harmless bit of the coronavirus’s spike protein. After the protein is made, your cells break down the vaccine’s mRNA. Despite what some misinformed online “researchers” might claim, the vaccine doesn’t change your DNA. And no, the shots don’t contain microchips.