How Vaccines Were Really Invented

I am greatly pleased to say that I am finally in the process of being vaccinated for COVID-19, since Indiana University (the university I am currently attending) has a huge stockpile of vaccines reserved for students. I received my first dose of the Pfizer vaccine on 8 April 2021 and I am scheduled to receive my second dose on 29 April. Since lots of people like me are now receiving the vaccine for COVID-19, I decided that now would be a good time to write an article about the history of vaccines.

The story that most people have been told is that Edward Jenner, a white English man, single-handedly invented the very first vaccine—a vaccine for smallpox—in 1796. The reality, though, is much more complicated. Notably, many people are not aware of the fact that Jenner’s vaccine was an improvement on the much older procedure of inoculation, which originally independently developed in at least three different parts of the world (in China, West Africa, and the Ottoman Empire) and only later spread to Europe and the Americas through a process of cultural diffusion.

Smallpox inoculation

Inoculation is a medical procedure in which a person is deliberately infected with a mild form of a disease so that they will develop an immunity to it and therefore never catch a more severe form of the disease that might kill them. The first disease for which humans are known to have invented inoculation is smallpox, a horrible disease which caused characteristic severe fluid-filled blisters to erupt all over the infected person’s skin.

Smallpox was extremely deadly and extremely contagious. The disease was airborne, spread rapidly through in-person contact, and is estimated to have killed approximately a third of all those who caught it. For most human history, the disease is estimated to have killed at least 400,000 people every year. In the twentieth century alone, it is thought to have killed at least 300 million people. Those who survived the disease were usually left with severe scars all over their bodies, including their faces. Some survivors of the disease were also left permanently blind.

If scabs from a person infected with the disease were administered to a healthy person through a small cut in the skin, however, then the person would develop a mild form of the disease that was almost never fatal, almost never resulted in blindness, left minimal scarring, and—most importantly of all—left the person completely immune to smallpox for the rest of their life.

ABOVE: Photograph from Wikimedia Commons of child in Bangladesh infected with smallpox in 1973. The World Health Organization (WHO) declared that smallpox had been successfully eradicated in Bangladesh four years later in 1977.

ABOVE: Photograph from Wikimedia Commons of a man with severe scarring and blindness caused by smallpox

Smallpox inoculation in China

The earliest known definite reference to smallpox inoculation in any surviving text from any culture occurs in the Douzhen Xinfa, a medical text written by the Chinese physician Wan Quan that was originally published in the year 1549. Wan Quan clearly understood the basic principle behind inoculation. He writes, as translated by Boying Ma:

“The toxic qi may be weak or strong, so the disease also presents different. Sometimes it is rapid and dangerous, sometimes gentle and safe, sometimes violent and deadly. As the pox comes out, the toxin is eliminated too. Therefore, once one had suffered from smallpox, he will not be infected with it forever.”

Unfortunately, Wan Quan does not give a detailed description of the process of inoculation itself and merely notes that, in some cases, smallpox inoculation unexpectedly induced menstruation in women.

More extensive references to inoculation appear in later Chinese medical and alchemical texts dating from the sixteenth through eighteenth centuries.

ABOVE: Chinese illustration from c. 1911 showing a pre-eighteenth-century Chinese method for inoculating against smallpox

Smallpox inoculation in West Africa

Smallpox inoculation also seems to have independently developed in West Africa, possibly around the same time that it developed in China. Unfortunately, there are no detailed written records from West Africa from this time period describing the process of inoculation.

Nonetheless, as will be important later in this article, by the time western Europeans started shipping enslaved African people across the Atlantic Ocean to the Americas in large numbers in the seventeenth century, inoculation was apparently already widely practiced among many West African peoples.

Smallpox inoculation in the Ottoman Empire

Finally, the practice of smallpox inoculation also independently developed at some point in around the seventeenth century CE among impoverished members of various Christian ethnic communities that were living under Ottoman dominion, including Circassians, Georgians, and Greeks.

The Venetian physician Giacomo Pylarinius records in a letter written in 1716 that a Greek woman introduced smallpox inoculation to the city of Constantinople for the first time in around the year 1660. In the year 1700, a particularly severe smallpox epidemic struck. This epidemic seems to have demonstrated the effectiveness of inoculation to many Christians, leading it to become a widespread practice among Christians in the Ottoman Empire more broadly.

Pylarinius claims that Ottoman Muslims were reluctant to accept inoculation, because they believed that it went against Divine Providence. Eventually, some Ottoman Muslims did adopt inoculation, but it remained more common among Ottoman Christians.

ABOVE: Illustration of a street in the bazaar of Athens in 1821, which may give some impression of what small Greek towns in the Ottoman Empire looked like

Emanuel Timonius’s report of inoculation in the Ottoman Empire

In around late 1713, the respected Greek physician Emanuel Timonius, who was living in Constantinople, wrote an influential letter describing the Ottoman practice of inoculation and its remarkable effectiveness at preventing smallpox. The English naturalist John Woodward read Timonius’s letter and presented a summary of it to the Royal Society in London in January 1714. Woodward summarizes:

“The writer of this ingenious discourse [i.e., Timonius] observes, in the first place, that the Circassians, Georgians, and other Asiatics, have introduced this practice of procuring the smallpox by a sort of inoculation, for about the space of forty years, among the Turks and others at Constantinople.”

“That although at first the more prudent were very cautious in the use of this practice; yet the happy success it has found to have in thousands of subjects for these eight years past, has put it out of all suspicion and doubt; since the operation, having been performed on persons of all ages, sexes, and different temperaments… none have been found to die of the smallpox.’

“…They that have this inoculation practised upon them are subject to very slight symptoms, some being scarce sensible they are ill or sick: and what is valued by the fair, it never leaves any scars or pits in the face.”

Woodward’s summary of Timonius’s letter was consequently published in the journal Philosophical Transactions of the Royal Society. This became the first report of inoculation to circulate widely among educated people in the west.

ABOVE: Portrait of John Woodward, who delivered a summary of Emanuel Timonius’s letter about smallpox inoculation in the Ottoman Empire to the Royal Society in London

Introducing Lady Mary, inoculation campaigner extraordinaire

In March 1717, Lady Mary Wortley Montagu (lived 1689 – 1762), an English aristocratic woman, arrived in the Ottoman Empire with her husband Lord Edward Wortley Montagu, who was serving as the British ambassador to the Sublime Porte. Lady Mary was well aware of the horrors of smallpox, since her brother had died of the disease in 1713. She herself had caught the disease in 1715 and, although she survived, it left her severely scarred.

Shortly after arriving in the Ottoman Empire, Lady Mary witnessed old Greek women practicing inoculation and immediately recognized its potential to save potentially millions of lives. On 1 April 1717, she wrote a letter to a friend back home in Britain describing the practice as she had observed it and declaring her resolve to introduce it to Britain. She writes:

“The small-pox, so fatal, and so general amongst us, is here entirely harmless, by the invention of engrafting, which is the term they give it. 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 parties for this purpose, and when they are met (commonly fifteen or sixteen together) the old woman comes with a nut-shell full of the matter of the best sort of small-pox, and asks what vein you please to have opened.”

“She immediately rips open that you offer to her, with a large needle (which gives you no more pain than a common scratch) and puts into the vein as much matter as can lie upon the head of her needle, and after that, binds up the little wound with a hollow bit of shell, and in this manner opens four or five veins. The Grecians have commonly the superstition of opening one in the middle of the forehead, one in each arm, and one on the breast, to mark the sign of the Cross; but this has a very ill effect, all these wounds leaving little scars, and is not done by those that are not superstitious, who chuse to have them in the legs, or that part of the arm that is concealed.”

“The children or young patients play together all the rest of the day, and are in perfect health to the eighth. Then the fever begins to seize them, and they keep their beds two days, very seldom three. They have very rarely above twenty or thirty in their faces, which never mark, and in eight days time they are as well as before their illness. Where they are wounded, there remains running sores during the distemper, which I don’t doubt is a great relief to it.”

“Every year, thousands undergo this operation, and the French Ambassador says pleasantly, that they take the small-pox here by way of diversion, as they take the waters in other countries. There is no example of any one that has died in it, and you may believe I am well satisfied of the safety of this experiment, since I intend to try it on my dear little son.”

“I am patriot enough to take the pains to bring this useful invention into fashion in England, and 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. But that distemper is too beneficial to them, not to expose to all their resentment, the hardy wight that should undertake to put an end to it. Perhaps if I live to return, I may, however, have courage to war with them.”

In March 1718, Lady Mary had an elderly Greek practitioner in Constantinople inoculate her eldest son Edward under the supervision of the British Embassy surgeon Charles Maitland. Thus, Edward Wortley Montagu became the very first western European ever to undergo a recorded inoculation for smallpox.

ABOVE: Portrait of Lady Mary Wortley Montagu and her eldest son Edward, who became the first western European to be inoculated for smallpox in March 1718

When Lady Mary returned to England, she became an ardent public supporter of inoculation. In April 1721, a devastating epidemic of smallpox broke out in England. Lady Mary had Charles Maitland, who had previously overseen the inoculation of her son Edward, perform the procedure himself on her daughter. This is the very first recorded inoculation performed in Britain—or, indeed, any part of western Europe.

Lady Mary publicized her daughter’s inoculation and wrote letters to various British lords and officials to promote inoculation. Catherine of Ansbach, the Princess of Wales, who had personally suffered a particularly severe case of smallpox in 1707 and barely survived, agreed with Lady Mary that inoculation was worth giving a try. In August 1721, she arranged an experiment for seven prisoners from Newgate Prison who had already been sentenced to death to be given the option of being inoculated for smallpox instead. All seven prisoners survived the inoculation with minimal scarring. As a reward for having agreed to take part in the experiment, they were released.

Seeing that the procedure was indeed safe, Princess Catherine had both her own daughters inoculated for smallpox in April 1722. In September of that year, Lady Mary published an article under a pseudonym advocating in favor of inoculation.

ABOVE: Portrait of Caroline of Ansbach, the Princess of Wales, who supported Lady Mary’s efforts to promote inoculation

Introduction of smallpox inoculation from West Africa to North America

Meanwhile, at the exact same time that people in Britain were starting to learn about inoculation from reports from the Ottoman Empire, British colonists in North America were also starting to learn about inoculation from the Black people they enslaved, many of whom originally came from cultures in West Africa that had practiced inoculation for centuries.

An Akan man who had been inoculated against smallpox at a young age when he was living among his native people was captured and sold to European slave traders, who shipped him across the Atlantic and eventually sold him in Boston as a slave. In around 1706, he was given as a gift to the Puritan minister Cotton Mather, who renamed him “Onesimus” after an enslaved man who is mentioned in the apostle Paul’s Epistle to Philemon. In around mid-1713 or thereabouts, Mather happened to ask Onesimus if he had ever caught smallpox and Onesimus taught him about the West African practice of inoculation.

Months later, in early 1714, Mather read John Woodward’s summary in Philosophical Transactions of the Royal Society of Emanuel Timonius’s letter about smallpox inoculation in the Ottoman Empire. He was evidently quite impressed, since he had already learned about the practice from Onesimus. He wrote a letter to the Royal Society, declaring:

“I am willing to confirm to you, in a favourable opinion, of Dr. Timonius’ communication; and therefore, I do assure you, that many months before I met with any intimations of treating the smallpox with the method of inoculation, anywhere in Europe; I had from a servant of my own an account of its being practised in Africa. Enquiring of my Negro man, Onesimus, who is a pretty intelligent fellow, whether he had ever had the smallpox, he answered, both yes and no; and then told me that he had undergone an operation, which had given him something of the smallpox and would forever preserve him from it; adding that it was often used among the Guramantese [i.e., the Akan people] and whoever had the courage to use it was forever free of the fear of contagion. He described the operation to me, and showed me in his arm the scar which it had left upon him; and his description of it made it the same that afterwards I found related unto you by your Timonius.”

Another Puritan minister named Benjamin Coleman interviewed many enslaved Black people in Boston and confirmed that smallpox inoculation was widely practiced in West Africa and that it was highly effective at preventing death from smallpox.

ABOVE: Portrait of the New England Puritan minister Cotton Mather, who learned about smallpox inoculation from an enslaved man named Onesimus and subsequently became a vocal supporter of the practice

The very first public inoculation campaign in North America

On 22 April 1721, the British passenger ship HMS Seahorse arrived in Boston from Barbados. The day after the ship arrived, one of the sailors disembarking from the ship fell ill with smallpox in a house in Boston Harbor. Although the sailor in question was quickly quarantined, at least nine other sailors who had already been exposed to him quickly fell ill as well. The disease rapidly spread throughout the whole city, resulting in the most devastating smallpox epidemic in the city’s history.

After the outbreak of the epidemic, Cotton Mather and several other Puritan ministers became fierce supporters of inoculation and helped initiated a campaign to inoculate as many people in the city as possible. With Mather’s support, a white physician named Zabdiel Boylston imitated the same technique that enslaved Black people living in the city had learned in their West African homeland.

The campaign faced immense public opposition and backlash. Inoculation efforts were intensely criticized in the press. At one point a mob surrounded Mather’s home and threw a pipe bomb in through the window. Boylston was forced to perform many of his inoculations in secret under the cover of night, wearing a disguise to travel from house to house.

Nevertheless, despite the backlash, the campaign was remarkably successful. Boylston published an account of his inoculation efforts titled An Historical Account of the Small Pox Inoculated in New England. According to his account, he successfully inoculated approximately 248 people. Approximately 15% of those who caught smallpox naturally died of the disease. By contrast, of those whom Boylston inoculated, only 2% died.

ABOVE: Photograph of the title page of Zabdiel Boylston’s account of his own efforts to inoculate the people of Boston against smallpox using techniques learned from enslaved Black people

Smallpox and cowpox

Over the course of many decades, inoculation against smallpox became increasingly widespread in the English-speaking world. Then, in 1768, an English physician named John Fewster (lived 1738 – 1824) made a remarkable accidental discovery. He performed a smallpox inoculation on two boys with the last name Creed, but discovered that only one of the two boys had a reaction to the inoculation. He learned that the other boy had previously experienced an infection of cowpox, a disease that dairy workers often contracted from cattle that caused very mild localized blisters.

It was a widely held belief among English farm workers at the time that those who had contracted cowpox were immune to smallpox. Most physicians did not take this belief seriously and regarded it as nothing more than a foolish superstition. Fewster, however, began to suspect that the popular superstition was actually correct.

At dinners for the Convivio-Medical Society at the Ship Inn in Aleveston, England, Fewster regularly raised the possibility that people who had previously been infected with cowpox might be immune to smallpox. One of the people present at these meetings was a young medical apprentice named Edward Jenner (lived 1749 – 1823). Jenner’s biographer John Baron, who had many conversations with Jenner himself, writes in his Life of Edward Jenner 1.48:

“Dr. Jenner has frequently told me that, at the meetings of this Society, he [i.e., Fewster] was accustomed to bring forward the reported prophylactic virtues of cowpox, and earnestly recommend his medical friends to prosecute the inquiry. All his efforts were, however, ineffectual; his brethren were acquainted with the rumour, but they looked upon it as one of those vague notions from which no accurate or valuable information could be gathered, especially as most of them had met with cases in which those who were supposed to have had cowpox had subsequently been affected with smallpox.”

Although the other doctors may have dismissed Fewster’s claims, Jenner went on to become a physician himself and he never forgot what he had heard about cowpox potentially conferring immunity against smallpox.

ABOVE: Portrait of the English physician Edward Jenner, who developed a vaccine for smallpox

Edward Jenner’s experiments

Jenner first experimented with alternative inoculation techniques in November 1789, when he inoculated his eldest son Edward for swinepox, which he believed was a form of the same disease that was also known as cowpox. He subsequently inoculated Edward for smallpox multiple times, with the boy only developing mild symptoms each time.

On 14 May 1796, Jenner conducted what has been considered his most convincing experiment. He took cowpox blisters from a milkmaid named Sarah Nelmes and used them to inoculate a healthy eight-year-old boy named James Phipps in both arms. Phipps contracted a mild fever and felt mildly uneasy for a few days, but displayed no further signs of infection.

To test whether this inoculation against cowpox would truly give Phipps immunity to smallpox, Jenner conducted a second inoculation on the boy for smallpox. The boy had no reaction whatsoever. Jenner inoculated Phipps for smallpox again and once again found that the inoculation produced no reaction.

It is often misleadingly stated that Jenner deliberately infected Phipps with smallpox. Technically, he did give Phipps the virus, but it was through the inoculation procedure that was already in common use at the time; he didn’t give Phipps the full infection. All the same, Jenner’s experiment would almost certainly violate modern ethics rules for medical experiments.

In total, Jenner tested his vaccination technique on twenty-three patients—including his own infant son Robert Jenner—before he published his findings in 1798 in a book titled An Inquiry into the Causes and Effects of the Variolae Vaccinae: A Disease Discovered in Some of the Western Counties of England, Particularly Gloucestershire, and Known by the Name of the Cow Pox.

ABOVE: Illustration from 1802 showing a smallpox inoculation (left) and a cowpox inoculation (right) sixteen days after the inoculations were administered

In the beginning, many people resisted vaccination. Even many physicians remained skeptical. Jenner himself could not explain why vaccination worked, since the germ theory of disease had not yet been developed. All he could demonstrate was that vaccination was effective at preventing smallpox. Fortunately, the British Parliament recognized the importance of Jenner’s findings and gave him a grant to establish a vaccination clinic in London. As word of Jenner’s experiments spread, he became hailed as an international hero, the very first hero of modern medicine.

Jenner is rightly praised for having invented and promoted the smallpox vaccine. It is important to remember, however, that Jenner’s vaccine was merely an improvement on the already-existing treatment of inoculation, which had originated outside of Europe centuries earlier. If inoculation hadn’t already existed, Jenner almost certainly would never have invented the vaccine.

Thus, while Jenner definitely deserves some credit for his own work, we need to remember all the other people who contributed to the development of the smallpox vaccine, including the anonymous Chinese Daoist alchemists, West African folk doctors, and poor ethnic minorities in the Ottoman Empire who first experimented with inoculation, the woman who introduced it to Britain, the enslaved Black man who introduced it to Boston, and the prisoners from Newgate Prison who were experimented on to prove that it worked.

ABOVE: Anti-vaccination political cartoon by James Gillray published in 1802, representing Edward Jenner vaccinating patients with cowpox, causing the patients to grow cow-like body parts

Eradication of smallpox

Thanks to the smallpox vaccine, smallpox no longer exists. The last recorded case of the disease was in 1977. In 1980, the World Health Organization (WHO) declared that the disease had been completely globally eradicated. This means that, unless some very evil person deliberately reengineers the virus and releases it into the wild, no one will ever catch smallpox again. It is almost impossible to assess how many millions of people the smallpox vaccine has saved from death, blindness, and disfigurement.

The smallpox vaccine also laid the groundwork for the development of vaccines for other diseases as well. Polio, another disease that once killed millions and left millions crippled for life, is now on the brink of being globally eradicated, thanks primarily to vaccines. Even as new and dangerous diseases like COVID-19 continue to emerge, vaccines remain our greatest defense against them.

As of the time I am writing this, the COVID-19 pandemic is confirmed to have killed over 567,000 people in the United States alone and over three million people worldwide. COVID-19 has officially killed more Americans than World War II. In fact, COVID-19 has killed more Americans than any war in history, except for the American Civil War. Our best hope of ending this abysmal and devastating pandemic is through vaccination. Therefore, anyone who is eligible to receive a vaccine for COVID-19 should do so.