America’s Original Immunization Controversy: The Tercentenary of the Boston Smallpox Epidemic of 1721

Abstract

The CoVID-19 pandemic marks the 300th anniversary of the Boston smallpox epidemic of 1721, America’s first immunization controversy. Puritan minister Cotton Mather learned of inoculation for smallpox from Onesimus, a man enslaved to him. When the disease broke out in May 1721, Mather urged Boston’s physicians to inoculate all those vulnerable to the disease. Zabdiel Boylston, alone among his colleagues, decided to proceed with the procedure, igniting a heated debate that occasionally grew violent. The division between the advocates and detractors of inoculation were as deep as religion and politics. Puritan ministers supported inoculation, asserting their right to control the lives of their flock. Challenging them were a secular class of medical professionals that proclaimed primacy in medical matters. The controversy was inflamed by a nascent newspaper industry eager to profit from the fear of contagion and the passionate debate. Despite the furor and physical risk to himself and his family Boylston inoculated 282 persons, of whom only 6 died (2.1%). Of the 5759 townspeople who contracted smallpox during the epidemic, there were 844 deaths (14.7%). In America’s first effort at preventive medicine Boylston established the efficacy of inoculation, which helped support its acceptance in England, and later in the century, the adoption of Edward Jenner’s technique of vaccination in 1796.

A Bold Proposal

“Of all the foes our ancestors faced – hardship, famine, pestilence, Indian and foreign wars,” wrote James Mumford, surgeon and historian, “the most dreaded was smallpox.” ¹ Zabdiel Boylston (1676-1766), whose inoculations in 1721 saved hundreds of lives, described how victims were ravaged by the disease:

Purple spots, the bloody and parchment pox, hemorrhages of blood at the mouth, nose fundament and privates; ravings and delirium; convulsions, and other fits; violent inflammation and swelling in the eyes and throat; so that they cannot see, or scarcely breathe, or swallow anything, to keep them from starving. Some looking as black as the stock, others as white as a sheet; and some, the pock runs into blisters, and the skin stripping off, leaves the flash raw … some have been filled with loathsome ulcers, others have had deep, and fistulous ulcers in their bodies, or in their limbs or joints, with the rottenness of the ligaments and bones. Some who live are cripples, others idiots, and many blind all their days …. ²

The threat of smallpox, therefore, was on the mind of the Reverend Cotton Mather (Figure 1, 1663-1728), New England’s leading Congregationalist cleric and scion of prominent Puritan ministers. Alongside his fire and brimstone theology he had wide-ranging scientific interests, corresponding with the Royal Society and reporting on the natural history of colonial America. ³

Figure 1.

Peter Pelham, artist (1728). Cotton Mather. Library of Congress.

Among his primary interests was medicine. Having survived 2 outbreaks in 1688 and 1702, he thought that smallpox had a 12-to-14-year cycle. By 1714 he dreaded that an outbreak would soon occur.

In his household was Onesimus, an enslaved man, who was provided to the reverend by his grateful congregation. The acquisition of a servant required asking whether the enslaved person ever had smallpox. “Yes and no,” Onesimus answered; he had had smallpox, but from an inoculation. ⁴ Mather learned when an outbreak occurred in the Barbary villages where the enslaved persons were imprisoned, pus was collected from the sores of the first victims to inoculate the rest, preserving the slavers’ grim investment.

In 1716 Mather remembered Onesimus’ story when he read the 1714 volume of the Philosophical Transactions of the Royal Society (it took that long for a copy to reach him). Immediately after one of his own articles was another that described inoculation in Constantinople. Mather made the connection: If there was a way to prevent the disease, why not inoculate all those who were vulnerable?

In July 1716 he wrote a letter with his bold hypothesis. The society never responded to Mather’s idea. The letter lay buried in its records until it was unearthed by George Kittredge of Harvard University who published it in 1912, nearly 200 years later. ⁴

Outbreak and Experiment

On October 28, 1720, the merchant sloop Seahorse arrived from the Canary Islands by way of Tortuga Island with smallpox on board. The selectmen of the colony tried to confine its victims to a pest house in the remote reaches of Boston Harbor. The precaution did not prevent the discovery on May 8 of one of the Seahorse’s crew in town sick with smallpox. The outbreak soon blossomed to full force by June. ⁵

Mather lost no time to put forth the strategy he had come up with 5 years previously. On June 6 he wrote to each of Boston’s 14 physicians and asked them to inoculate all those who had not contracted the disease since the last outbreak in 1702. This meant not only many of the newcomers that doubled the population of the town to 11 000, but all of its children. ⁶

At first the doctors ignored Mather, dismissing his proposal as just another of his tiresome jeremiads. This one, however, created a stir: It was potentially dangerous, on par with his writings on witchcraft and devilry that helped fire a credulous flock to torture and hang 20 victims in Salem in 1692.

Zabdiel Boylston alone was the only physician willing to give inoculation a try. Like Mather he was the third generation of one of Boston’s founding families, the sixth of twelve children born to Thomas Boylston, a physician and surgeon. Like all but one of the town’s physicians, Zabdiel Boylston did not go to medical school nor did he receive formal training. He learned medicine by apprenticeship to his father and another of the town’s physicians. Before the epidemic Boylston held no special reputation as a practitioner.

Scarcely aware of the existence of inoculation, Boylston relied on articles that Mather showed him in the Transactions and Onesimus’ descriptions. On June 26 Boylston made a deep incision in his six-year-old son’s arm one-quarter inch in length, deep enough to accommodate a pea. Into it he placed a full drop of infective pus and mixed it with the blood that filled the cavity. He placed a walnut shell over the incision and held it in place with a length of cloth. He did the same on the boy’s thigh. He then repeated the procedure on a Black man enslaved to him and the latter’s son. ⁵

Each developed the dread disease. Boylston sat vigil with his son as high fevers and bouts of vomiting developed 6 days after the procedure. Pocks broke out over his face. As the boy suffered the father waited anxiously for the disease to continue its crescendo to the edge of death. Instead, on the ninth day the fever broke. The sores began to crust over and heal. His other 2 patients followed the same frightening but relatively benign course, given that it was still smallpox. Convinced of the success of the experiment, Boylston went on with his inoculations, including another of his children, a twelve-year-old boy, and one of Mather’s sons. ⁷

Outrage

Such news was impossible to conceal in the small town confined to a peninsula just one-and-a-quarter square miles in size. When word got out about Boylston’s inoculations, “it raised,” in Mather’s words, “a horrid Clamour.” Invectives were so vicious that in his mind “the Devil had ‘taken a strange Possession of the People.’” ⁸ In his history of Massachusetts Thomas Hutchinson wrote, “Many sober, pious people were struck with horror, and were of the opinion that, if any of his patients should die, he ought to be treated as a murderer.” ⁹

Unable to respond to the mob that harassed him, Boylston tried to justify his actions in an advertisement in the July 10-17 issue of the Gazette, one of the town’s two newspapers. He described the procedure and assured that his son, the enslaved man, and the latter’s son had fully recovered. He promised to follow up in the upcoming weeks with more news. He then invited his colleagues to come and examine his patients. ⁷

But he made no statement that he was halting the experiment. Boylston did not quarantine his inoculated patients, even though they were as infective as those who naturally contracted the disease. This left him open to the valid criticism that he was deliberately spreading the disease and putting the town at risk. ¹⁰

Boylston’s erstwhile colleagues immediately censured him. William Douglass (1691-1752) was the leader of the group and Boston’s only physician with a formal degree in medicine. He had come to colonial America only 5 years before with the anticipation that his education in Edinburgh, Paris, Uretcht, and Leiden, where he received his degree in 1712, would assure a large and profitable medical practice. ¹⁰ His training also imbued him with the traditional attitudes of the English medical caste system that placed educated physicians as aristocrats on its top rung. Apothecaries occupied the bottom position, just below surgeons.

Inoculation gave Douglass an issue to assert his primacy of the Boston medical community. Writing under the pseudonym “W. Philanthropos (‘lover of mankind’)” in the Boston News-Letter of July 17-24 he disparaged Boylston as more of a “cutter for the stone” and apothecary than a true physician. ⁷ He dismissed Mather as “a credulous, vain preacher” interfering with physicians’ work. ¹⁰ At the instigation of Douglass and his fellow physicians on July 21 the selectmen convened and formally prohibited Boylston from performing inoculations in the town. ⁵

“Douglass … was defending the integrity of the medical profession against the interference of those whom he considered credulous laymen. … no one should accept all the quaint … accounts from the Levant and from untutored Negroes,” wrote John Blake of the National Library of Medicine. ⁸ Douglass, for all of his chauvinism and elitism, asserted the primacy of an elite, professionally trained (of which he was the sole member), to make medical decisions.

Mather had to answer the religious question of whether smallpox was a test of faith and whether inoculation was thus contrary to God’s law. One of his fellow reverends, William Colman, gave a succinct answer in a catechism on inoculation: “Yes, it is God’s Judgment but at the same time He sends His Judgment He shows as a Way to escape the Extremity and Destruction at least, if not the touch of it.” ¹¹

Mather and the Boston ministry defended Boylston in a letter in the July 27-31 issue of the Gazette. They wrote:

Thanks be to God we have such a One among us, and that so many poor Miserables have already found the benefit of his gentle and dexterous hand. We that have stood by and seen his tenderness, courage, and skill in that hazardous Operation cannot enough value the man and give praise to God. ⁷

Boylston continued his inoculations despite the injunction, doing more each month to a peak of 103 in November alone. ² He and his family were threatened with violence, a bomb once thrown into his house. On November 14 Mather also had a bomb thrown through his window, the device landing unexploded on the floor. It came with a note: “Cotton Mather … You Dog, and Damn You, I will Enoculate You with this, with a Pox to you.” ¹¹

The brouhaha brought forth a third competing paper, the New England Courant, supported by Anglican opponents of Mather and physicians opposing inoculation. Its printer, James Franklin, would fade from history. On its pages was a personality who wrote under the name Silence Dogood, a middle-aged widow whose patina of modest charm contrasted with entertaining iconoclasm. Franklin gladly printed Silence’s letters, which attracted a wide readership, not knowing that her identity was his younger brother and apprentice Benjamin. ⁵

First Clinical Trial

The furor died as the epidemic burned itself out in the spring of 1722. On February 26, 1722, the Selectmen made an official statement in the Courant that nobody in Boston was known to have smallpox. After a final 6 inoculations in May Boylston agreed to stop doing the procedure. “In this quiet way the inoculation experiment was finished,” wrote John Barrett, a pediatrician and author of a prize-winning essay on the episode. ¹¹

Eventually 282 persons in Boston were inoculated, the most by far by Boylston. Of those undergoing the procedure only 6 died (2.1%). Of the 5759 townspeople who contracted smallpox during the epidemic, there were 844 deaths (14.7%), a relative risk of natural versus inoculated smallpox of 6.9 (3.2 - 15, P < .0011). ¹² The success of the Boston experiment in establishing the efficacy and relative safety of inoculation led to its adoption in both the American colonies and England as the primary means of preventing smallpox until Edward Jenner developed vaccination in 1796. ⁵

Mather and Boylston’s decision to use an untried procedure on hundreds of their fellow citizens, including their neighbors and families, was unprecedented. Boylston visited London in December 1724, where he was hailed with saving hundreds of lives. At the suggestion of his admirers in the Royal Society, of which he was made a member in July 1726, Boylston published a monograph where he listed every person he inoculated and whether the result was survival or death. ²

The publication documented America’s first clinical trial. Author Stephen Coss quoted medical historians to place Boylston’s achievement. ⁵ To John Blake of the National Library of Medicine it was “the most important experiment in America in preventative medicine.” Medical historians Otho Beall of the University of Maryland and Richard Shryock of Johns Hopkins wrote, “The history of immunology, with all its ultimate values in overcoming infectious disease diseases began—above the folk level and on meaningful scale—in the Boston epidemic of 1721.”