The beginning of the anti-vax movement is often dated to the late 1990s, when a now-retracted paper based on manipulated data falsely linked the MMR vaccine to autism. But the anti-vax trend is far older than that—in fact, it’s as old as vaccines themselves.

Many communities have valid reasons to be cautious of government medical mandates: the Tuskegee syphilis experiment and forced sterilization programs are just two of medicine’s many dark moments. But some people’s opposition to safe and effective vaccines stems from reasons that are a little more … well, silly. Here are the stories of eight of history’s most misguided anti-vaxxers.

1. William Douglass (1691-1752)

In the early 1700s, Douglass was the only doctor in Boston with an actual degree in medicine. That’s probably why he felt so confident about mocking a new method of preventing smallpox introduced by three unlikely people: Cotton Mather, a Puritan minister best remembered today for his promoting the Salem witch trials; Onesimus, an enslaved African man; and Zabdiel Boylston, an apothecary and surgeon without a medical degree. Onesimus had taught the other two men about a common practice in his homeland, in which children were deliberately exposed to minor cases of smallpox by applying pus from an infected person into a scratch on their arms. The children would get mildly sick, but usually recovered, and thereafter enjoyed lifelong immunity from the deadly scourge. Mather and Boylston were so impressed with the idea that they decided to test it out in 1721, when a smallpox epidemic hit Boston.

Douglass was less impressed. He wrote a series of newspaper articles and pamphlets, calling Mather “a credulous vain preacher” and Boylston “illiterate” and a “dangerous quack” [PDF]. He didn’t bother to acknowledge Onesimus.

Douglass wasn’t the only spouter of anti-vax sentiment in town. James Franklin and his better-known younger brother, Benjamin, published a newspaper that contained editorials, articles, and even poems satirizing the medical advance. Yet another person threw a grenade through Mather’s window late one night with a note attached that read, “Cotton Mather, you dog, damn you! I’ll inoculate you with this” [PDF]. Luckily for Mather and his family, the grenade failed to explode.

Despite all the protests, it was Onesimus, Mather, and Boylston who won in the end. By the time the next smallpox epidemic hit Boston a decade later, Douglass had transformed from an anti-vaxxer to an inoculation devotee who offered the practice to his own patients. Douglass had a change of heart after Boylston published detailed records and fatality rates that proved his new method was much safer than allowing oneself to catch smallpox naturally. The affair turned out to be history’s first major (successful) use of medical statistics.

2. Benjamin Moseley (1742-1819)

Moseley was a rich, well-educated, and highly regarded physician in Georgian England, best known for his investigations into new consumer products like coffee and sugar. Unfortunately, he proposed that coffee cured headaches, coughs, asthma, gout, and kidney stones, and was a great antidote to opium addiction, while the idea that sugar causes cavities was an "old woman’s bug-bear, to frighten children.” His take on vaccinations wasn’t much better.

In 1796, Edward Jenner had taken Onesimus’s concept and improved on it, showing that by using pus from cowpox instead of actual smallpox, patients received the same immunity as before, but now without the risk of catching the more serious disease or passing it on to others. This new method, called vaccination after the Latin word for cow, vacca, quickly caught on.

Of course, every new discovery has its detractors, and Moseley was one of the loudest. He gave vaccination his own new names, including cowmania, cow-dung, and even bovine syphilis (they didn’t catch on). Moseley published accounts of the supposed negative side effects of vaccination in numerous pamphlets and journal articles. According to him, they included whooping cough and insanity. He cited supposed case studies of a woman whose face "began to resemble that of an ox,” and a young boy who grew cow hair all over his body.

Like many anti-vaxxers today, Moseley speculated that the long-term consequences of vaccination might be even worse: “Can any person say what may be the consequences of introducing […] a bestial humour, into the human frame, after a long lapse of years? Who knows, besides, what ideas may rise, in the course of time?” He meant that women might want to have sex with cows: “Owing to vaccination the British ladies might wander in the fields to receive the embraces of the bull.”

It sounds silly, but Moseley was an early articulator of a still-common belief: that vaccines contain something unnatural, dirty, or toxic that can infect our healthy bodies. We’ve changed the focus of this fear from cow pus to mercury or formaldehyde, but the underlying idea is at least 200 years old.

3. Ferdinand Smyth Stuart (1745-1814)

Stuart was a great-grandson of King Charles II and called himself a doctor, though he probably didn’t actually have a medical degree. He was also one of Moseley’s loudest supporters. Adding to the warning about horny women with horns, Stuart published a story of a young boy who changed his behavior after vaccination: His “former natural disposition absolutely changed to the brutal, so that it ran upon all fours like a beast, bellowing like a cow, and butting like a bull.”

This pamphlet—which had the incredible title of £30,000 for the cow-pox!!! An address to the British Parliament, on vaccination (of the greatest importance to mankind)—came with a cover illustration showing Jenner and other pro-vaccination doctors tipping basketfuls of babies into the mouth of a monstrous, oozing cow that’s sick not only with cowpox, but with leprosy, plague, and ulcers. The title referred to £30,000 that the British Parliament had recently granted Jenner as a reward for his discovery. Stuart, like many anti-vaxxers since, pointed to the money as a motivation for why “this monster [vaccination] has found not only a multitude of friends but worshippers, who prostrate themselves before him, and encourage his voracious appetite.”

Stuart also pioneered the method of discrediting vaccines by associating them with his political enemies. In this case, because he was British and writing in 1807, his rant went after Britain’s greatest enemy: the French. “Are we to worship—to applaud—or even to submit to Evil, to Buonaparté, or to Vaccination, because they have for some time been prosperous? No! Never let us degrade our honor, our virtue, or our consciences by such servility," he wrote.

Speaking of Napoleon, he was an early adopter of vaccination—having had his firstborn son vaccinated even before he was baptized—and a huge fan of Dr. Jenner, once saying after Jenner had asked for a favor, "Ah, Jenner, I can refuse him nothing."

4. Jules Guérin (1801-1886)

Louis Pasteur discovers the rabies vaccine. Culture Club/Getty Images

Dr. Guérin’s great adversary was Louis Pasteur, who became a global celebrity for developing the first vaccines for diseases other than smallpox, including rabies and anthrax. But at the time of the clash between Guérin and Pasteur, those discoveries lay in the future. In 1880, Pasteur had just presented his findings on his very first vaccine (to prevent chicken cholera) to France’s Académie Nationale de Médecine, only to be interrupted and mocked by Guérin. He asked Pasteur over and over to explain how he had made the vaccine, and then pretended not to understand the explanations. He mocked Pasteur for not being a real doctor (Pasteur had two doctorates in chemistry and physics, but never received a medical degree). Guérin caused such chaos that the meeting ended early. When the Académie met again a week later, Pasteur announced that he would never “respond to the indiscreet, intemperate, and unhealthy curiosity of M. Guérin,” then addressed him directly, saying, "we will see who emerges lame and bruised from this match.”

Guérin took the challenge literally: He launched himself at Pasteur and had to be physically restrained by the other researchers. The next day he denounced Pasteur as a liar and demanded a duel.

What made this escalation even stranger is that Pasteur was 59 and partially paralyzed from a stroke, and Guérin was 80 years old. Luckily the two old men never faced one another with pistols. Guérin backed down after it became clear that Pasteur had the support of the Académie’s board of directors.

Guérin’s also argued that germs play no part in infecting wounds. Luckily for us, the research of Pasteur, Joseph Lister, and others won out, while Guérin has been mostly forgotten.

5. John Pitcairn, Jr. (1841-1916)

A Scottish immigrant to the U.S., Pitcairn worked his way up from servitude to extreme wealth, founding PPG Industries and shaping the modern-day oil and natural gas industries. When his son Raymond was vaccinated in 1885, he experienced a minor infection; this brief illness may have been caused by the vaccine or may have been a coincidence. Either way, Pitcairn became a fervent anti-vaxxer, and used his riches to promote the cause.

He was a follower of Swedenborgianism, a Christian denomination based on the mystic visions of a 17th-century philosopher that had an upswing in popularity in the United States during the 19th century. Other Swedenborgians included Johnny Appleseed, Robert Frost, and Ralph Waldo Emerson. Although Swedenborg himself hadn’t had much to say about medicine, his followers quickly became associated with homeopathy, a belief that disease was not caused by germs but by spiritual disorders. Doctors and medicine, therefore, should stop studying the physical and instead focus on the mental and even theological health of an individual.

For Pitcairn, this approach to disease meant that vaccines were morally reprehensible. He defined vaccination as "the putting of an impure thing into the blood.” More than that, he thought that any physical contamination left its mark not only on the body but also on their immortal self, and therefore injecting someone with a vaccine was the same as deliberately scarring their soul.

Pitcairn’s real impact came not his exact beliefs, but from his wallet. In 1906 he organized the Pennsylvania Anti-Vaccination League (of which he was made president for life), the first anti-vax organization to have significant money and support. But it didn’t succeed in repealing any vaccine mandates, and so in 1908, Pitcairn helped to found the Anti-Vaccination League of America. He wrote, “We have repudiated religious tyranny; we have rejected political tyranny; shall we now submit to medical tyranny?" Despite being a millionaire himself, Pitcairn was also quick to point the finger at the supposed pecuniary incentives of vaccinators [PDF]: “There is no money in the cause we represent; it is the cause of truth, the cause of freedom, the cause of humanity; but it is said that there are 20 million dollars invested in vaccine farms in this country.” Despite being appointed by the governor of Pennsylvania to a special commission to investigate vaccinations, Pitcairn never did manage to change any laws.

After his death, his sons Harold and Raymond (who had recovered from that infection) continued to support the Anti-Vaccination League and similar causes, where they always stood up for liberty against government intervention—even fighting against laws intended to end child labor.

6. Henning Jacobson (1856-1930)

A Lutheran minister and Swedish immigrant to Massachusetts, Jacobson probably never expected to become a famous name, but any law student—particularly one who’s been paying attention to cases over the last year and a half—will have heard of the Supreme Court decision Jacobson v. Massachusetts.

In 1899, yet another smallpox epidemic hit Boston and the surrounding area. The Cambridge Board of Health responded by ordering all inhabitants of the city to be vaccinated. When the epidemic ended in 1903, 270 people had died—but 485,000 people (about 83 percent of the city) had been vaccinated, likely saving the lives of many. Jacobson was not one of them. He and his son refused to be vaccinated, and when the city attempted to force him, Jacobson took them to court.

Starting at the Middlesex County district court, then the state supreme court, and finally the United States Supreme Court, Jacobson and his lawyers pleaded his case that God, not vaccines, would protect him. One lawyer asked, “Can the free citizen of Massachusetts, who is not yet a pagan, not an idolator, be compelled to undergo this rite and to participate in this new—no, revised—form of worship of the Sacred Cow?”

The Supreme Court didn’t take the idea that vaccines were "a barbarous ceremonial of blood-poisoning” and cow worship very seriously. In a 7-2 ruling, they found that the government did have the right to impose mandatory vaccines, because “real liberty for all could not exist” if individuals used their liberty to injure others.

7. Lora Little (1856-1931)

Little was born in a log cabin, but in many ways her activities could fit right in with the 21st-century world of Twitter and Instagram. She believed in the importance of whole wheat, brown rice, and “Hindu-Yogi” breathing practices. She wrote a newspaper column titled “Health in the Suburbs,” advertised her services as a health teacher, and traveled internationally to give lectures on how to "eat right, live right." She ran for the Oregon House of Representatives in 1913—only one year after women received full voting rights in that state.

Little was most famous, however, for her anti-vax campaigns. She was the editor of The Liberator, an anti-vax newspaper named after the famous antislavery paper of the pre-Civil War era. Little’s Liberator ran for only five years, but was well-regarded by other anti-vaxxers as far away as Britain. In 1906, she published Crimes of the Cowpox Ring: Some Moving Pictures Thrown on the Dead Wall of Official Science, which gave the profiles of 336 “victims” of vaccination. Some of these deaths may indeed have been the result of vaccination; in the days before antibiotics, without modern sterilization procedures, it was possible for the wound caused by an injection to become infected, even fatally so. Other deaths, though obviously tragedies, have less of a connection. Little included her own son, Kenneth, in the list of vaccine deaths, though he died of diphtheria eight months after receiving a smallpox vaccination. It seems unlikely that the two events had anything to do with one another.

Like many today, Little believed in the curative power of nature and common sense. “Trust nature, is a safer motto than trust the doctor,” she wrote. She argued against the “artificial pollution” of vaccines. On the other hand, she didn’t believe in any kind of medication; disease was not caused by germs, but by the body cleaning itself, according to her. As long as you followed the right diet, got the right exercise, and stayed clean, all your diseases and injuries would "quickly disappear.” That’s right: everything from tetanus to cancer cured by fresh air, garden frolics, and skipping breakfast.

8. Joseph Pulitzer (1847-1911)

In addition to inventing yellow journalism and establishing the Pulitzer Prizes, Joseph Pulitzer was an early media promoter of the antivax movement. In 1901, he owned the Post-Dispatch newspaper of St. Louis and saw his chance to sell papers when a vaccination scandal hit the city.

Diphtheria was a major killer of children in 1901, and like today, antibodies were used as a treatment to save lives. The antibodies were produced by horses injected with diphtheria toxin. Eventually, physicins could draw blood from the horses, extract the antibodies, and inject them into suffering children. This all worked fairly well—except when horses were exposed to diseases other than diphtheria. In September 1901, a horse named Jim had his diphtheria antibodies drawn, and shortly afterwards developed tetanus. His antibodies were supposed to be destroyed, but due to a mix-up, they were instead sent out to doctors across the city. The first child injected with Jim’s antibodies was a young girl named Bessie Baker. She quickly recovered from her bout of diphtheria, but died of tetanus five days after receiving the shot. Thirteen children in St. Louis died from these contaminated injections, including both of Bessie’s siblings.

Pulitzer began writing attention-grabbing headlines that brought nationwide attention to the tragedy. Unfortunately, only a few months later in October 1901, tetanus contaminated a batch of smallpox vaccine from cows accidentally exposed to a tetanus-infected horse in Camden, New Jersey. This time 11 children died. Again, Pulitzer turned tragedy into a money-making operation.

Ironically, due in large part to Pulitzer’s promotion of the scandal, the very next year President Theodore Roosevelt signed the Biologics Control Act. For the first time, the government had the power to determine who was allowed to manufacture vaccines and to oversee quality control. This act allows the FDA to regulate vaccines today, and to make sure that no accidents like the ones in St. Louis and Camden ever happen again.