At the tail end of a pandemic (we hope!) vaccines are in the news. There are huge disparities in COVID-19 vaccination rates marked by class, race, and geography. Critics question the system of tiered eligibility as many essential workers like those in the food industry are not yet eligible for the vaccine. Others don’t trust pharmaceutical companies to tell the truth about the side effects or efficacy of their immunizations. Still more believe that compulsory vaccination violates their personal liberties and that vaccine mandates are a slippery slope into a fascist state. But we’re here to tell you that vaccination has always been controversial. Many of the concerns people have now about the COVID-19 vaccine were voiced in the past about the original smallpox vaccine. A few years ago, when we were the History Buffs Podcast, we released an episode about the History of Immunizations and Anti-Vax Movements. In light of a renewed interest in vaccination, we’re revamping that tired old episode. This week, we attempt to add some historical context to our current vaccine debates by telling you the story of the invention of vaccination, its impact, it’s opponents, and the issues surrounding them. 

Transcript for The OG Vaccine: Smallpox, Cowpox, and the Procedure that Changed the World

Researched and Written by Marissa Rhodes, PhD

Recorded by Marissa Rhodes, PhD and Elizabeth Garner Masarik, PhD

Marissa: If there’s one thing we’ve learned in the past few months, it’s that public health policy in general, and vaccine policy in particular are controversial. President Biden has dramatically increased COVID-19 vaccine production and distribution. At the time of this recording, 15% of all Americans and 50% of seniors over the age of 65 have been vaccinated for COVID-19. Still, our pandemic problems persist. There are huge disparities in vaccination rates marked by class, race, and geography. Critics question the system of tiered eligibility as many essential workers like those in the food industry are not yet eligible for the vaccine. 

Others don’t trust pharmaceutical companies to tell the truth about the side effects or efficacy of their immunizations. Still more believe that compulsory vaccination violates their personal liberties and that vaccine mandates are a slippery slope into a fascist state. Particularly alarming is the fact that rates are on the rise in some areas of the country again despite the successful mass vaccination efforts. But we’re here to tell you that vaccination has always been controversial. Many of the concerns people have now about the COVID-19 vaccine were voiced in the past about the original smallpox vaccine. A few years ago, when we were the History Buffs Podcast, we released an episode about the History of Immunizations and Anti-Vax Movements. In light of a renewed interest in vaccination, we’re revamping that tired old episode. This week, we attempt to add some historical context to our current vaccine debates by telling you the story of the invention of vaccination, its impact, it’s opponents, and the issues surrounding them. 

I’m Marissa

and I’m Elizabeth

Marissa: and we are your historians for this episode of Dig. 

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Marissa: Some historians argue that immunization, in the form of inoculation, was invented on the Indian sub-continent around the year 1000 CE as a means of preventing smallpox. The process was supposedly derived from one of the eight branches of Ayurvedic medicine, called agada‐tantra, which dealt with the therapeutic use of toxins in small doses. Inoculation could be performed by introducing infected materials like puss or scabs from a sick person with needles in the skin of a healthy person. This was the preference of Indian practitioners whose Ayurvedic traditions had always favored the use of needles to introduce foreign materials to the skin. Alternatively, infected material could be insufflated, or snuffed up into the nose.[1] 

Elizabeth: From India, the practice of inoculation is supposed to have spread to China, West Asia, and Africa in the following centuries. Inoculation was not introduced to Europe until relatively late in history. Medieval India, China, and Muslim West Asia were home to robust medical disciplines while medieval Africa and Europe relied more on folk healing. Our first verified documentation of inoculation dates to 1549 in a treatise published in China. For this reason, some historians argue that inoculation was developed by the Chinese who, it should be noted, preferred insufflation as the delivery method. It’s difficult for us to pinpoint inoculation’s exact origins, however, because Chinese practitioners guarded this intellectual property zealously until the 17th century.[2]

Marissa: Regardless of the practice’s debatable origins, we know that inoculation was introduced to Western medicine by way of Constantinople some time after 1650. Venetian physician Giacomo Pylarini traveled to Turkey in 1716 and wrote that inoculation had been introduced to Constantinople in 1660 by a Greek woman and that it was a common practice in the Christian community there. This possibility is supported by the fact that it was an old Greek practitioner who inoculated the first Europeans in 1721 in Turkey. These first inoculates were the Montagu children.

Elizabeth: English aristocrat Lady Mary Wortley Montagu and her family had resided in Constantinople since her husband, a British diplomat, had been stationed there in 1716. Lady Mary had witnessed first-hand the suffering that was caused by smallpox. In 1713, her younger brother William Pierrepoint, had died from the disease. He had only been 20 years old. He left behind a young wife, a two-year-old son, and an infant daughter.

Lady Mary Wortley Montagu | Public Domain / Wikimedia Commons

Marissa: In December of 1714, Lady Mary herself contracted smallpox. We have detailed records of what this experience was like for her. Though she was a privileged, wealthy woman, her experience still gives us some idea of how traumatic it was to suffer from smallpox in the 1700s. Lady Mary’s illness began with a fever that lasted several days. She tossed and turned, alternating between hot flashes and cold sweats. Her head pounded and the room swayed as she vomited into a washbasin. Terrified that she had one of the many deadly diseases that were endemic to London, and that she may pass it on to her vulnerable children, Lady Mary sent her son Edward and his nurse away in the early morning hours.

Elizabeth: She was terrified that she may have smallpox but since it took several days to display the telltale signs, she waited nervously to see what would become of her. Since she was a wealthy woman, her physicians attended her dutifully each day. A surgeon bled her by cutting a vein in her arm, and the physicians administered daily rounds of emetics and laxatives which caused her to vomit and evacuate her bowels. They prescribed a drink of ground up saltpeter and bezoar stone. Saltpeter is an ingredient in gunpowder and was made by spreading a blanket over decaying vegetation and then sprinkling it with urine. Bezoar stone is calcified hair and food that is found in the stomachs of animals. (We mentioned the use of bezoar stones in early modern medicine in our medicinal cannibalism episode). I can’t imagine that tasted very good.

Marissa: So she’s doing all of these horrendous things. She knows she’s sick but she doesn’t yet know what she’s sick with. She also doesn’t know if she’s passed on the illness to her child. So… she waits. She suffers and waits to see what her fate and that of her child will be. After a few days, her worst fears were confirmed when red bumps begin to appear on her skin. When her smallpox diagnosis was confirmed, she inquired frantically about the welfare of her child and his caretakers assured her that he was “still unspotted.”

Lady Mary’s physicians were concerned as the signature red bumps filled with a clear liquid which, over time, turned into an opalescent gray/white. They had the appearance of large, flattened pimples. These were the “pocks.” Lady Mary herself watched in horror as the pocks grew into one another, swelling her face into one massive, grotesque blister. She was fed nothing but oatmeal or barley-gruel boiled with figs, tamarind, or plums. She drank small beer acidulated with lemon or lime and diluted sweet German wine.

Elizabeth: One week into the illness, her fever abated. The puss filling her pocks hardened into a beeswax yellow and the redness subsided but the swelling continued. The skin on her face was stretched nearly to the point of bursting. Her fingers were so swollen she could not hold a pen. Her mouth was filled with sores as well on her tongue and the roof of her mouth. Her tongue was so swollen that it became unbearably painful to swallow. She became unable to speak.

On the tenth day of her illness, she took a turn for the worst. Her fever spiked yet again, higher than ever. The pustules all over her body began to burst and their contents stank horribly. Her monthly period arrived, an added inconvenience in her debilitated state. While Lady Mary fought for her life in this very critical stage of the illness, London’s High Society gossiped about her family’s fate and whispers about how, even if she survived, she’d have lost her beauty forever.

Marissa: James Brydges, Earl of Carnarvon, wrote to a friend in Scotland, “Poor Lady Mary Wortley has the smallpox… just as it began (to her great joy) to be known she was in favor with one whom every one who looks on cannot but love. Her husband, too, is inconsolable or the disappointment this gives him in the career he had chalked out of his fortunes.” While Lady Loudoun, also in a letter, wrote with more hope, “With a pair of eyes like Lady Mary’s, being marked is nothing.”[3] 

Elizabeth: Lady Mary was, however, unaware of their whispers. On day eleven, her swollen skin burst and strips of it fell away. Secondary infections began to take hold in her broken skin. Boils erupted where her blisters had been. A brown crust of scabs enveloped her entire body, leaking blood stained pus. Her temperature hovered between 103 and 105 degrees Fahrenheit as her breath began to rattle in her chest. She fell in and out of feverish delirium. As members of the London Society gathered for Christmas festivities, they talked in hushed tones about how Lady Mary would surely die.

On the fifteenth day of her illness, Lady Mary’s fever broke, this time for good. She momentarily gained consciousness, only to inquire about the health of her son. Her nurse assured her that he was “safe” (meaning he was free from smallpox and safe from this harrowing experience.) Upon hearing this news, Lady Mary fell into the deep sleep that began her recuperation.

Marissa: Though Lady Mary was known to be through the worst of it, it took weeks for her to lose her scabs, for the swelling to go down, and for her ragged breathing to recover. As the trauma of the illness faded, a fresh horror arose. Lady Mary was permanently disfigured. Her nose, lips, and eyelids remained swollen and red, her eyelashes had fallen out, and her skin was marked by reddish brown craters. Fully aware of the impact this disfigurement would have on her life, Lady Mary wrote the following poem shortly after seeing her new face for the first time:

How am I chang’d ! alas ! how am I grown

A frightful spectre, to myself unknown !

Where’s my Complexion ? where the radiant Bloom,

That promis’d happiness for Years to come ?

Then with what pleasure I this face survey’d !

To look once more, my visits oft delay’d !

Charm’d with the view, a fresher red would rise,

And a new life shot sparkling from my eyes !

Ah ! faithless glass, my wonted bloom restore;

Alas ! I rave, that bloom is now no more !

The greatest good the GODS on men bestow,

Ev’n youth itself, to me is useless now.

There was a time, (oh ! that I could forget !)

When opera-tickets pour’d before my feet ;

And at the ring, where brightest beauties shine,

The earliest cherries of the spring were mine.

Witness, O Lilly ; and thou, Motteux, tell

How much Japan these eyes have made ye sell.

With what contempt ye you saw me oft despise

The humble offer of the raffled prize ;

For at the raffle still the prize I bore,

With scorn rejected, or with triumph wore !

Now beauty’s fled, and presents are no more ![4]

Elizabeth: Now I know we just spent a really long time on Lady Mary’s experience but I think it’s important for people today, who have never experienced smallpox, to be aware of how traumatic this experience was for people. There was the physical experience of going through the illness, as well as the fear and anxiety for your loved ones, compounded by fear of death, and then for those who survived it, the long-term impact of disfigurement.

So it’s hardly surprising that, after this experience, Lady Mary was living with her family in Constantinople and she heard tell of old Greek practitioners who were performing operations on Turkish children that made them immune to the dreaded smallpox. In March 1718, she had her son inoculated there in Turkey. The practitioner made a small incision on his arm and introduced infected material to the wound. Her son was briefly and mildly ill but then he recovered and was presumably immune to smallpox. The procedure appeared to work as described.

Marissa: Three years later, Lady Mary and her family were living back in London when a horrific smallpox epidemic broke out in various areas around the country. London physicians had heard of the process of inoculation and they knew it was performed in the East but none of them had taken it upon themselves to bring the procedure to England. Eager to protect her daughter, Lady Mary, arranged to have her 5-year-old daughter inoculated. She invited several physicians to attend the procedure and observe the outcome. Much like it had three years earlier, the process resulted in a short, mild illness for the child and subsequent immunity. The British physicians in attendance were impressed.

G. Kirkland, 30 Plates of Small Pox and Cow Pox
G. Kirkland, 30 Plates of Small Pox and Cow Pox | Public Domain Mark (PDM) / Wellcome Collection

Since Lady Mary was an aristocrat who moved in the most elite of circles, the royal family heard about her daughter’s inoculation and the next year, 1722, they had the royal children inoculated for smallpox as well. Despite its acceptance by England’s elites, smallpox inoculation (which will come to be called variolation), met intense opposition from the start.

Elizabeth: Months after the royal childrens’ variolation, London vicar Edmund Massey preached against inoculation, or as he puts it “a Diabolical Operation, which usurps an Authority founded neither in the laws of nature or religion… and promotes increases of vice and immorality.”

In a sermon delivered at St. Andrews, Holborn, Massey declared that inoculation would promote unchristian behavior:

“…some are made honest for fear of a Prison; others continue Chaste for fear of infection; a great many are Just for fear of losing their Character; and no doubt several are Religious, more out of fear of going to Hell than any thing else. So that we see the worst of Evils have their Use, and in this sense, and by proper Reflection, we may make a Moral of the Devil himself. Should all restraints of this sort be taken away, were there no fear of Punishment in this Life, not belief of any in the next, should Inquiry and Reputation be join’d together, and Health be Handmaid to Uncleanness.”[5]

Marissa: Similar religious objections to inoculation spread like wildfire in the British colonies in New England. In 1721, the physician Zabdiel Boylston inoculated his son and two of his slaves after a smallpox infected ship from the West Indies arrived in Boston’s harbor. William Cooper and Cotton Mather published a pamphlet addressing the many disputes that had erupted in response. The pamphlet begins:

“The new method of receiving the Small-pox by Incision (or Inoculation) as ’tis commonly call’d) has been, you know, the Subject not only of plentiful Discourse, but of angry Debate and fierce Contention among us in this Town.”[6]

Elizabeth: Other critics argued that inoculation was not safe or effective. This was simply not borne out by the evidence and this became increasingly clear over time as the practice spread across Europe and its colonies. For example, the spread of inoculation in colonial Boston yielded impressive results. The 1721 smallpox epidemic infected 6,000 people in Boston and killed 844 of those people (that’s a mortality rate of 1/6). That same year, 286 Bostonians were inoculated and only 6 died (that’s a mortality rate of 1/46). When combined with statistics from Britain and continental Europe, the mortality rate of smallpox inoculation was adjusted to 1/50.  Given these statistics, Boylston saved at least 40 lives in Boston that year.

Marissa: The last objection to inoculation that we’ll mention here is a one that amounted to a valid challenge of the practice. People who were inoculated were contagious and could, therefore, spread the disease to others. In the American colonies, where population density was lower and quarantine was more effective, this was less of a concern. Bostonians were able to use a small island off the coast as an inoculation oasis. Due to this luxury, colonials were able to institute mass inoculation. In 1777 George Washington ordered that all Continental troops be inoculated once smallpox appeared in their ranks.

But in the densely populated urban centers in Europe, mass inoculation was risky and was never pursued for fear that it would spark an epidemic. It was during the eighteenth century that the vulnerability of the poor began to be noticed in Europe. Several physicians, such as John Coakley Lettsom and John Haygarth, expressed the desire to inoculate the poor in European cities but such ideas were never executed since the risk of contagion was so high.

This, however, was all about to change. Enter: vaccination.

Elizabeth: The origin story of vaccination begins in the most unlikely of places– on a cattle farm in rural Dorset, England. There, a farmer and cattle breeder named Benjamin Jesty believed that he had inadvertently immunized himself against smallpox in the course of his occupation. He and two of his milkmaids had contracted cowpox on the farm at some point. Both milkmaids, Ann Notley and Mary Reade, discovered their immunity when they attended family members who had contracted smallpox. Neither woman contracted the disease themselves.

Marissa: In 1774, there was a wave of smallpox cases in Jesty’s village. In a desperate attempt to protect his family, Jesty took his wife and two toddlers to a neighboring farm where he’d heard that one of the cows had an active case of cowpox. He used his wife’s knitting needle to collect infected material from the cow and to inoculate his wife and children. All three survived the procedure and their illness was mild. Fifteen years later, another smallpox epidemic visited the village. The local surgeon, Mr. Trowbridge, inoculated a few dozen children in the village with smallpox and the Jesty children were the only ones who did not contract the infection. Though Jesty never had any interest in publishing the results of his anecdotal study, he did inoculate other villagers with the cowpox at their request. Given the provincial and undocumented nature of Jesty’s experiment, it was largely forgotten or unknown. Jesty’s experiment was enshrined in local history with an inscription on his tombstone.[7]

Edward Jenner by James Northcote, oil on canvas, 1803, 1823 | Public Domain / Wikimedia Commons

Elizabeth: Meanwhile, after training with the celebrated surgeon John Hunter (who we discuss extensively in our forensic pathology episode), the young physician Edward Jenner returned to his hometown, a tiny village called Berkeley in Gloucestershire. Jenner spent several decades treating patients as a country doctor where he often treated milkmaids and other folks who spent time with animals. In his capacity as a physician, he regularly inoculated the locals for smallpox and he found that the operation did not take. His patients, especially those who had previously contracted cowpox, failed to contract smallpox after the infected material was introduced to their arms. Cowpox was an infectious disease that most often impacted cows but was also transmittable to humans.

Based on this observation, Jenner hypothesized that he might be able to immunize people against smallpox if he inoculated someone with infected matter from a person who contracted cowpox. He further hypothesized that he might be able to use the infected matter from the first cowpox-inoculated person to inoculate another and so on. This process would come to be known as arm-to-arm transmission. It wasn’t until 1796, however, that he was able to conduct an experiment to this end.

Marissa: Jenner successfully inoculated a little boy named James Phipps with infectious lymph material from the hand of a milkmaid named Sarah Nelmes. (Lymph is a clear fluid derived from blood plasma which contains white blood cells. When someone has an infection, lymph is secreted in the form of pus.) Nelmes had contracted the cowpox naturally in the course of her occupation. Several weeks after he introduced cowpox to Phipps’s system, Jenner attempted to inoculate him with smallpox. Lo and behold, the smallpox infection did not develop. Phipps was, indeed, immune to smallpox and even better, he was not contagious to others after the cowpox was administered.

Elizabeth: Jenner published a report of this experiment in 1798: An Inquiry into the causes and effects of variolae vaccinae (scientific name for cowpox). It is unclear if Jenner knew about Benjamin Jesty’s story at the time of his own experiments. It’s likely that Jenner made similar observations independently. However, Jenner and his followers became aware of Jesty at some point because, in 1805, the Jennerian Society invited him to London to celebrate his contribution to medical science. At the Original Vaccine Institution on Broad Street, Jesty was celebrated by the society and made to sit for a portrait by the painter M. W. Sharpe. The Jennerian Society presented him with gold-mounted lancets, the Sharpe portrait, and a long statement about their debt to him, signed by all members.

Marissa: Back to 1798, when Jenner’s publication hit the presses… The impact of Jenner’s publication is difficult to overstate. In London, Surgeon Henry Cline and George Pearson, a physician at St. Thomas’s Hospital advocated for the new practice and opened a public vaccine dispensary. At the time it was referred to as kine-pox inoculation but by 1803 it had come to be called vaccination (from vacca, the Latin for cow). German physicians C. F. Stromeyer and G. F. Ballhorn vaccinated 2,000 people in Hanover from 1799 to 1801.

Elizabeth: American physician Benjamin Waterhouse read Jenner’s essay and immediately sent for a sample of lymph material from England. It arrived in 1800, soaked into threads and protected in a sealed bottle. Waterhouse immediately vaccinated his 5-year-old son and six of his servants. Weeks later, he tried to infect them with smallpox material harvested from a patient suffering from the disease. They were immune. Waterhouse subsequently advocated for mass vaccination with the support of Thomas Jefferson. Waterhouse greedily guarded the cowpox strain he’d acquired even as he publicized it widely. Some American physicians paid substantial licensing fees to obtain some lymph from him. Other physicians in New England were forced to obtain material from England after Waterhouse refused to share.

Marissa: Waterhouse’s monopoly on vaccine material in the United States had disastrous consequences for some. Desperate for cowpox material, physicians were harvesting lymph from untrusted sources. In Marblehead, Massachusetts 68 people died after they were mistakenly infected with full-blown smallpox rather than vaccine.[8] Thankfully, most physicians were committed to making the vaccine available to the public. In 1802, New York physician Valentine Seaman opened the Institute for the Inoculation of the Kine-Pox which provided free vaccinations to the poor.

Elizabeth: By 1801, Jenner’s Inquiry appeared in all of the main European languages and over 100,000 people had been vaccinated in England alone. The British Empire’s long tentacles allowed for vaccination to be introduced as far as China by 1805. Surgeons traveling with the East Indian Company advocated for the practice and brought lymph material with them on their travels. Swiss-born physician Jean de Carro was instrumental in delivering the vaccine to Eastern Europe, the Ottoman Empire, and Russia. De Carro made an unsuccessful attempt at shipping the vaccine to India in 1799. The material arrived contaminated by the voyage. He tried again in 1802, with a strain he’d obtained from Italian cows. The sample arrived in Mumbai in 1802 where it was used to vaccinate the first Indian on June 14. This supply was sustained arm-to-arm all the way to Sri Lanka, Madras, and Calcutta.

Marissa: While Waterhouse had luck obtaining cowpox strains preserved on threads, arm to arm transmission was still the primary mode of vaccination. Continued vaccination relied on the constant presence of cowpox pustules from which to harvest infected material. It took impeccable timing and constant ministration to the vaccination process. Remote areas were unable to obtain live samples and countries without developed medical infrastructures were unable to maintain a living sample for long. For example, all of Thailand remained unvaccinated until 1840 when they successfully obtained a cowpox strain from a boat arriving from Boston.[9]

Elizabeth: As you can imagine, transporting lymph material sometimes took elaborate planning. In 1803, King Charles IV of Spain commissioned royal physician Francisco Xavier de Balmis to bring smallpox vaccination to Spanish America. De Balmis and his assistants brought 22 abandoned children on their voyage by ship. They vaccinated the boys in sets of two throughout the trip so that someone would have fresh pustules at any given time. When the ship docked at Caracas, there was only one visible cowpox pustule left on one of the boys.  Using material from this pustule, De Balmis initiated arm-to-arm vaccination in South America. All 22 children were eventually adopted and educated in Mexico at the expense of the Spanish Crown.

Marissa: As the merits of vaccination became apparent, physicians urged their respective governments to outlaw inoculation. For example, Jean de Carro wrote: “It is inconsistent for a government to encourage vaccination and not forbid inoculation.” While most governments stopped short of outlawing inoculation, many countries passed legislation that regulated inoculation and encouraged vaccination. In 1813, the U.S. Congress passed  “An Act to Encourage Vaccination” which established a National Vaccine Agency. Baltimore physician James Smith was appointed the National Vaccine Agent. The Act also required that the U.S. Post Office carry mail weighing up to 0.5 oz. for free if it contained smallpox vaccine material.

Edward Jenner vaccinating his son, held by Mrs Jenner
Edward Jenner vaccinating his son, held by Mrs Jenner | Wellcome Collection

Elizabeth: By 1820, the demographic impact of vaccination was undeniable. Before vaccination, smallpox was the primary cause of infant mortality. One physician discovered that smallpox killed one out of every ten Swedish children in the 1760s. In Berlin from 1758 to 1774, there were 6,705 smallpox deaths. Of these, 5,876 (88%) occured in children who were 5 or younger. Likewise, the London bills of mortality from a similar period showed that 50% of all deaths occured in children 5 or younger.[10] After the advent of vaccination, life expectancy rose around the world. Smallpox hospitals saw less traffic and eventually closed down. Smallpox deaths decreased by 91% in Sweden.[11] From 1811 to 1820, the London Bills of Mortality documented 7,858 deaths from smallpox—down from 18,447 deaths in the last decade before vaccination (1791-1800).[12]

Marissa: While vaccination was much safer than inoculation, it did come with certain risks. The method of arm-to-arm transmission sometimes resulted in unwanted infections like hepatitis and sexually transmitted infections. It was also clear that cowpox transmitted from human to human lost potency over time. For this reason, scientists continued to innovate.

As early as 1805, physicians in Naples began experimenting with animal vaccines as alternative to the arm-to-arm method. They would intentionally grow the cowpox virus on the leg of a calf and harvest the infectious material from there. In 1810, the director of the Neapolitan vaccine service, Gennaro Galbiati, retrovaccinated a calf with human vaccine lymph. He then harvested the resultant animal lymph and used it to vaccinate humans. Galbiati was please with the results:

“1. Vaccination performed with vaccine from the cow manifests its effects much more energetically, without being more dangerous or less protective than humanized virus.”

“2. Vaccination performed with virus from the cow offers the advantage that no other diseases can be communicated by it.”[13]

This arm-to-arm alternative remained unknown outside of Naples until the 1860s.[14]

Elizabeth: Disease, in general, was rampant in nineteenth-century Europe and physicians became aware that arm-to-arm vaccination was occasionally aiding in the spread of other infections, most notably Syphilis. French doctors identified the Neapolitan practice of animal vaccination as a way to minimize the likelihood of transmitting Syphilis during the process of vaccination. In 1864 a team of French physicians studied the effectiveness of using animal hosts and subsequently advocated for that method. From that point forward, vaccination by calf became popular in continental Europe and America. The practice was not legalized in Britain until 1881 and arm-to-arm vaccination remained prevalent there until it was banned by law in 1898.[15]

Marissa: In 1836, English physician Edward Ballard developed a way to boost the potency of the vaccine. Rather than using old strains that had been passed arm-to-arm for decades, Ballard suggested using new strains of cowpox from cows that suffered recent infections. After vaccinating humans with these new strains, he harvested lymph from their pustules and retrovaccinated cows to boost the strain’s potency yet again. This new, and more effective method, quickly became the standard for smallpox vaccination.

Elizabeth: These vaccine developments made the practice of smallpox inoculation (or variolation as it had come to be called) obsolete. Britain’s Vaccination Act of 1840 outlawed variolation and provided for free vaccination for all British infants. A subsequent British Vaccination Act (1853) made smallpox vaccination mandatory for all infants in the first three months of life. Parents who failed to vaccinate their infants faced steep fines or imprisonment. This was far from the first attempt at compulsory vaccination. States all over the world had attempted mandatory vaccination laws for decades. Napoleon’s sister, Marianne Elisa Bonaparte, Princess of Lucca and Piombino, was the first ruler to introduce mandatory vaccination in 1805. Massachusetts was the first state in the United States to mandate vaccination for school children in 1855.

Marissa: While vaccination had always had its detractors, vaccine mandates stimulated a new wave of passionate critics. The 1853 British vaccine mandate is a good case in point. In Britain, the Guardians of the Poor (local authorities) were responsible for enforcing compulsory vaccination. Over the next 20 years, anti-vaxxers banned together to elect Guardians of the Poor who they knew would not enforce the mandate. This loophole was closed in 1874 by another Vaccination Act which compelled local authorities to act in accordance with the national law. Angry at what they perceived as an overreach of national authority, and supported by a hostile, anti-vax constituency, the Guardians of the Poor in Keighley (Yorkshire) quashed prosecutions against anti-vax parents and fired their appointed vaccination officer. Enraged at this insubordination, the local health board incarcerated the seven Guardians in York Castle. Anti-vax locals retaliated and, after several skirmishes, the Guardians were released.[16]

In addition to local action, angry Brits established activist associations such as the National Anti-Vaccination League (1866), and the Anti-Compulsory Vaccination League (1874).[17] Other countries experienced similar movements: the American Anti-Vaccination League had its first meeting in New York City in 1882.  The same year, abolitionist Frederick Douglass expressed the opinion that mandatory vaccines violated personal liberty.

Elizabeth: In Germany and Switzerland, the Lebensreform movement expressed its opposition to vaccination. Vaccine opposition groups began forming a few years before the vaccine mandate was signed into law in 1874. Before long, Germany’s Imperial Association Opposing Compulsory Vaccination had 300,000 members.[18] Despite the opposition and hostility to the German vaccine mandate, the legislation had an impressive impact on the nation’s health:

“After the law of 1874 went into effect the annual mortality in Prussia fell so that between 1875 and 1886 the average yearly mortality per 100,000 of population was only 1.91. On the other hand, in Austria, where the lax vaccination and revaccination requirements remained unchanged, the mortality of smallpox during about the same period (1872-1884) increased, varying between 39.28 and 94.79 per 100,000 of population…. In 1897, there were but five deaths from this disease in the entire German Empire with a population of 54,000,000.”

Marissa: Most countries responded to anti-vax activism in similar ways. In Britain, a Royal Commission conducted a comprehensive survey of the vaccination issue and delivered several reports to Parliament in the 1890s. The commission’s findings were used to craft the 1898 Vaccination Act which retained compulsory vaccination but allowed for exemptions for conscientious objections. In most countries, exemptions served as a compromise that defused the worst of the hostility by opponents.

Elizabeth: The end results were mixed. Many communities continued to vaccinate for smallpox as a matter of course but occasional smallpox epidemics did occur, especially in areas with low vaccination rates. This happened often in the United States. Because of its federalist system and passionate investment in states’ rights, a national vaccination mandate eluded them for decades after they became common in Europe. As a result, the USA had pockets where vaccination was neglected. For example, an outbreak occurred in Muncie, Indiana in 1897 and another in Milwaukee, Wisconsin in 1925.

Marissa: Still, generally speaking, the public’s confidence in vaccine science increased over time. Scientists used Edward Jenner’s philosophy to develop and manufacture vaccines for other diseases such as Cholera, Diptheria, Rabies, Polio, and Pertussis. Though there is plenty more vaccine history in the 20th century, we’re going to bring this episode to a close and perhaps plan another episode in the near future dealing with vaccination in the 20th century, but first I wanted to ask Elizabeth if there’s anything she wanted to discuss? Because I think that there’s a couple of really interesting points here that I didn’t have time to flesh out in the episode and one of them that I want to make sure we talk about for a second, is the practice of vaccinating or inoculating one’s children servants or slaves.

Elizabeth: Yeah, that’s a good one.

Marissa: Because they don’t have a choice. I mean, with children, it’s like, well you’re their parents so I suppose before they’re adults that you kind of do have the say. But for your slaves or your servants, they’re kind of being compelled to go along with this whether they want to or not, right? And you’re purposely giving them smallpox, at least in the beginning, with inoculation.

Elizabeth: Yeah! I mean I guess for me, it’s surprising how many people were willing to experiment on their own children in the first place. Like, “Let’s see if this works, kids,” you know? “I’m gonna give you this disease that is known to be quite deadly and horrific and let’s see if this little experiment that I’m doing is working.” So an answer to your question, like I think it’s apples and oranges. You know, experimenting on your kids is something very much different than experimenting on your servants and slaves. And so in your question, that makes me think of Deirdre Cooper Owens book, Medical Bondage, about the origins of American gynecology and the “Father of American Gynecology.” This guy named Sims did all of his experiments on enslaved women. So I think it’s an important thing for you to point out that you know so much of this experimentation is done on people who don’t have a lot of say. So I’m thinking of the 22 orphaned boys that are brought on this ship and passed cowpox throughout the voyage, right? They don’t have any say on whether they’re going to participate in this or not. They’re forced into it.

Marissa: Right. They’re kind of treated like just meat. Like, “Oh you’re just a human body that we can….” Like, “You’re kind of useless because you’re an orphan. So let’s just inoculate you with the cowpox to just see what happens.” And it’s sort of disconcerting. And what’s disconcerting to me is how little the ethical implications of all that is really discussed. Because if you read a lot of histories of medicine, specifically histories of vaccination, they don’t really bring that up. They’re just like, “Oh yeah, this person just vaccinated his servants or vaccinated his slaves or whatever” and “They’re amazing and they’re a hero!” But think about what that actually looks like at the time. It’s sort of troubling to me…

Elizabeth: Very troubling, yeah.

Marissa: …and kind of reiterates the dark past that history of medicine sometimes covers up behind progress, you know? And then the other thing was the vaccine mandate issue, because you know, obviously now in the 21st century, we deal with the anti-vax movement. And I would say that most of the anti-vax movements are not anti-vaccination so much as their anti-compulsory vaccination?

Elizabeth: Right.

Marissa: And I think that was also the case in the 19th century. They were a little better about articulating that. They were called the Anti-Compulsory Vaccination League for example, in the UK. But now I always used to think “Well, anti-vaccine people aren’t anti-science. They’re just anti-compulsory vaccination.” But now that COVID has happened, we know there are truly a lot of people who are very anti-science. And I don’t know how I feel about it anymore. Obviously, you can’t generalize but…

Elizabeth: Yeah that’s what I was gonna say. I mean there are so many different reasons. I think we’d have to have a whole other episode to even go through [all that]. But one thing that I think is it’s such a fear of the unknown. And I think so much of it is brought about by fear. The reason I say that is (I’m actually thinking and I wanted to ask if you have seen this before) have you watched the HBO series of John Adams? It was a mini series, probably came out like 10 or 15 year ago.

Marissa: With Paul Giamatti?

Elizabeth: Huh? Oh yeah it was Paul. Yeah, yeah, yeah, yeah.

Marissa: Okay, yeah. I don’t think I finished it but, I started watching it.

Elizabeth: So in that, Abigail Adams actually inoculates her children. And so in the series, there’s actually a doctor that’s going around and he’s got a kid in the back of a cart (kind of harkening back to what you’re talking about, people who don’t really have any say in this medical experimentation). So this kid is driving around and has an active case of smallpox with the pustules all over him. He comes to the Adams’s house and takes a little bit of the pus from the pustules and then inoculate the children. And then they all sick and you see them sick. And I think I think the daughter almost dies from it.

Marissa: I remember that episode so I did definitely see that one. I can remember they were very anxious, like awaiting to see what would happen, what course their illness would take.

Elizabeth: Right, right. I mean it’s a TV show so, you know, there’s questions about how that really went down. But the reason I bring it up is, again, this fear that “What if you’re the one in the 50?” Or gosh, I don’t even know death rates for, say, the COVID-19 vaccine. You know, one in a million that is going to die. So much of it is fear of being forced into taking that gamble, I guess.

Marissa: Yeah, it makes sense and it’s arguable whether we actually have vaccine mandates in the US. Because a lot of people would say that the fact that you have to be vaccinated to go to school, that is the vaccine mandate. But it’s not really, because you have other options than going into a public school.

Elizabeth: You have other options. Yeah, exactly. And there’s there’s all kinds of options you can take.

Marissa: Yeah, so I don’t even think we don’t have mandatory vaccination on the scale that they have in the 19th century at all in Europe. I wonder if we have been untouched by smallpox for so long that we aren’t afraid of it like they were at the time, you know? They had, genuinely, mass vaccination mandates where like, “You were born. You got a vaccination. The end.”

Elizabeth: Well, I mean you could equate it to the polio vaccine. There’s really not very many people alive today that experienced the polio the amount that people that were living in the early 20th century did, right? Even with measles or mumps, after that generation that has experience with it is gone, like the fear of it almost is gone as well. Which I think, also kind of fuels some of this anti-wanting to vaccinate your children… until it happens! And then people were like, “Oh my God, holy crap! Like this a real horrible disease and I’ve made a terrible mistake.”

Marissa: Right? Like I actually anticipated a lot more people being ambivalent or against the COVID vaccine than are. But almost everybody in my life, even people who are kind of reticent about other vaccinations, are super into wanting to get the COVID vaccine. And I think it’s because we’re not so far removed from that experience, the experience of COVID I mean.

Elizabeth: Right. Yeah, perhaps.

Marissa: Okay, so let’s wrap it up.

Elizabeth: I think you’re right, though. I think maybe one of us should do something about the 20th century. I would definitely like to do something about polio for sure.

Marissa: Yeah, I would too. Definitely polio and the rabies vaccine stories is also really sick too.

Elizabeth: Oh?

Marissa: It’s a very international story, super interesting. So maybe a 20th century vaccine story would be nice? Okay, cool, thanks for joining us. Leave us ratings and reviews on Apple Podcasts. Visit our website at Email us at or you can visit us @dig_history on Twitter, or go to our Patreon, which we mentioned earlier the show. We always welcome your feedback and we always welcome your support. And also, if you have a COVID-19 story or even just a story from 2020 or early 2021 that feels like it’s part of this plague year (whether it’s the COVID plague or the plague of police brutality or any kind of plague), go to and share your story. It’s an open access archive that I’m one of the projects leads on it. We always want to hear people’s stories. And I thank you for sharing ahead of time if you do.

Elizabeth: Yes. Stay safe, and many, many good vaccinations to you!

Marissa: Yes, hahaha. Bye!

Elizabeth: Bye!


[1] Boylston A. (2012). The origins of inoculation. Journal of the Royal Society of Medicine, 105(7), 309–313.;  Kak S. (2008) Inoculation. In: Selin H. (eds) Encyclopaedia of the History of Science, Technology, and Medicine in Non-Western Cultures. Springer, Dordrecht.

[2] Boylston A. (2012). The origins of inoculation. Journal of the Royal Society of Medicine, 105(7), 309–313.

[3] The Speckled Monster: A Historical Tale of Battling Smallpox By Jennifer Lee Carrell


[5] A sermon against the dangerous and sinful practice of inoculation. Preach’d at St. Andrew’s Holborn, on Sunday, July the 8th, 1722. By Edmund Massey, M. A. Lecturer of St. Alban Woodstreet

[6] A letter to a friend in the country, attempting a solution of the scruples and objections of conscientious or religious nature, commonly made against the new way of receiving the small-pox. By a minister in Boston.



[9] The Greatest Killer, Smallpox in History, By Donald R. Hopkins · 2002, p. 145

[10] Rosen, History of Public Health, p. 101




[14] Henderson DA, Moss B. Smallpox and Vaccinia. In: Plotkin SA, Orenstein WA, editors. Vaccines. 3rd edition. Philadelphia: Saunders; 1999. Chapter 6. Available from:


[16] The Vaccination Controversy; the rise, reign and decline of compulsory vaccination, by Stanley Williamson, 2007.

[17] Bodily Matters The Anti-Vaccination Movement in England, 1853–1907 By Nadja Durbach · 2005



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