The great scourge of Thomas Jefferson’s era (1743-1826) was smallpox. Historians have estimated that perhaps as many as 2 billion people have died of smallpox in recorded history. That’s a pretty arbitrary figure, but it certainly indicates how serious the problem was. Modern epidemiology has not only eliminated smallpox as a threat to civilization but has been engaged in a protracted debate about whether to snuff it out altogether once and for all, or to keep a tiny bit of it alive in a handful of tightly secured vials in case we need to study it in the face of other disease epidemics. It was officially declared eradicated in 1980.

For most of human history, you either got it or you didn’t and then you either survived it or you didn’t. George Washington was infected by smallpox in Barbados in 1751. He survived, and though he was slightly disfigured, he was thereafter immune to the disease. It is possible that this early brush with smallpox saved the American Revolution 20 years later. In 18th-century Europe, 400,000 people died annually of smallpox.

By the time Jefferson was born in 1743, there was an experimental inoculation procedure, but it was quite dangerous and therefore highly controversial. The idea was to give healthy individuals a very tiny amount of actual smallpox under quarantine and very carefully controlled conditions and simply hope that the person’s immune system would be able to fight it off. Survival would immunize that individual for life. The procedure required many weeks of quarantine, fasting, puking, and rest, followed by a very light diet through convalescence. John Adams wrote a fascinating account of his own inoculation in 1764. He was 28 years old.

Young Thomas Jefferson’s first journey out of his native Virginia was to Philadelphia in 1766 to be inoculated. He would have undertaken the procedure in Williamsburg or Norfolk had it been available. He made the long journey (eight to 10 days in either direction) because he wanted to protect himself from the disease and study the procedure at the same time for possible incorporation into his own community at Monticello. With his characteristic taciturnity about personal things, Jefferson did not leave us a detailed account of the medical procedure, which required prolonged isolation, personal discipline and a great deal of patience.

Inoculation was first introduced in Europe 40 years earlier. Lady Mary Wortley Montague (1689-1762) had spent time in Turkey as the wife of the British ambassador to the Ottoman Empire. There she had witnessed inoculation in the zenanas (segregated women’s quarters) she visited. She called the procedure “engrafting,” which she described in an important “Letter to a Friend” on April 1, 1717. Mrs. Montagu’s brother had died of smallpox four years earlier and she herself had survived a bout of smallpox in 1715, but with her famous beauty disfigured. She had her five-year-old son Edward inoculated in the British Embassy in Turkey.

When she returned with her family to Britain, she became an outspoken advocate for the procedure. The English medical establishment decried inoculation and denounced Mary Montagu. Still, in 1721 when a smallpox epidemic broke out in England, she had her daughter inoculated in London. This was the first recorded use of the procedure in England. The medical establishment was slow to accept the efficacy of inoculation, which it regarded as an “oriental folk remedy.” It seemed counter-intuitive and just wrong-headed to give a healthy person a dose of smallpox to try to prevent her or him from getting it by accident.

Franklin Learns About Inoculation the Hard Way

New England Puritan minister Cotton Mather (1663-1728) first promoted inoculation in America. In 1706, Reverend Mather purchased a black slave he named Onesimus (from the Epistle to Philemon). Ten years later, Onesimus told Mather he had been made immune to smallpox in Africa by having the pus of an infected person rubbed on an open wound on his arm. This is known as the variolation method. Mather interrogated other slaves to learn more, confirmed the story, and became an advocate for inoculation. He was subjected to the usual criticism and pushback. An explosive device was thrown through the window of his home. In this instance, racism joined fear as a means of discrediting the medical procedure. What possible wisdom could come from a slave?

The smallpox plague that disturbed Britain in 1721 found its way that same year to Boston. Now Mather and Dr. Zabdiel Boylston, the only physician in Boston who supported the technique, offered their inoculation services to anyone who would trust them. Of the 242 people Boylston inoculated, only six died, or one in 40. Of those who did not undergo the procedure, one in seven died.

America’s greatest exemplar of the Enlightenment, Benjamin Franklin, became a passionate advocate of the procedure after his first son Franky died of smallpox on Nov. 21, 1736, at the age of four. Because Franklin was known to be a friend to inoculation, rumors spread in Philadelphia that Franky had died from the procedure. To set the record straight, the grieving father wrote an article in the Pennsylvania Gazette on Dec. 30, 1736: He had “intended to get [Francis] inoculated as soon as he should have recovered sufficient strength from a flux with which he had been long afflicted.” Franklin assured the public that his son “received the distemper in the common way of infection.”

In 1774, Franklin, who was an indefatigable creator of associations, societies, clubs and public institutions, including volunteer fire departments and lending libraries, established the Society for Inoculating the Poor Gratis to help the poor people of Philadelphia have access to inoculation. In his famous autobiography, Franklin wrote: “In 1736 I lost one of my sons, a fine boy of four years old, by the smallpox taken in the common way. I long regretted bitterly and still regret that I had not given it to him by inoculation. This I mention for the sake of the parents who omit that operation, on the supposition that they should never forgive themselves if a child died under it.”

Edward Jenner and the Fight to Vaccinate

As a young man, the future English physician Edward Jenner (1749-1823) overheard an English milkmaid say, “I shall never have smallpox for I have had cowpox. I shall never have an ugly pockmarked face.” Many years later, remembering the incident, Jenner, now a doctor, interrogated other milkmaids and then experienced one of the most important “eureka” moments in history. Without understanding how germs work, with no knowledge of anything called a virus, Dr. Jenner realized that cowpox (also known as kinepox) must be closely related to smallpox, and that surviving it seemed to make individuals immune to the more deadly disease. He reckoned that cowpox and smallpox must share some essential epidemiological element and since cowpox was neither lethal nor usually disfiguring, careful use of cowpox material would represent a superior protection against smallpox than variolation, which was a more dangerous procedure.

On May 14, 1796, Jenner inoculated an eight-year-old boy named James Phipps with kinepox pus. Phipps developed mild fever and discomfort. Ten days later he felt fine. Two months after that, Dr. Jenner inoculated the boy again, but this time with serum from a fresh smallpox sore. No disease developed. The smallpox vaccine had been born. Our term “vaccination” dates from this episode. Vaccination comes from the Latin word for cow, “vacca.” Jenner called the cowpox serum “vaccinia.” The terminology reminds us that all western vaccination stems from this moment in 1796.

No good deed goes unpunished, apparently, not even one that changes the history of the planet. In Britain, Edward Jenner was subjected to the usual harassment and ridicule. The paper he submitted to the Royal Society of England was rejected by none other than Sir Joseph Banks, one of Britain’s premier naturalists, botanists, and patrons of science. It took many years and the vaccination experiments of other physicians and scientists before Jenner’s work was vindicated.

Eventually, Jenner received worldwide recognition for his discovery. Devoted like Jefferson to the philanthropic principles of the Enlightenment, Dr. Jenner not only made no effort to enrich himself but devoted so much of his time and energy to promoting vaccination that he endured periods of real poverty. Finally, in 1802, the British Parliament voted him a reward of £10,000. Five years later he received £20,000 more from Parliament.

The true vaccine found its way to America thanks to Dr. John Haygarth of Bath. He sent some of Jenner’s material to Benjamin Waterhouse, a professor of physics at Harvard University. Waterhouse, in turn sent serum and reports of the vaccine’s efficacy to Thomas Jefferson, now the third president of the United States.

Dr. Edward Jenner discovered the true smallpox vaccine in 1796.

Jefferson’s Scientific Approach to Vaccines

In the new world, inoculation had a very rough reception. When John Dalgleish and Archibald Campbell began inoculating individuals in Norfolk, Virginia, an angry mob burned down Campbell’s house. Similar incidents occurred in Salem and Marblehead, Mass. In Charleston, S.C., an inoculation control law of 1738 imposed a fine of £500 on anyone providing or receiving inoculation within two miles of the city. A similar law was passed in New York City in 1747.

The measures in New England were so draconian that Benjamin Waterhouse noted the paradox: “New England, the most democratical region on the face of the earth voluntarily submitted to more restrictions and abridgements of liberty, to secure themselves against that terrific scourge, than any absolute monarch could have enforced.” (This, strangely prescient, anticipates the current debate about liberty versus public health). It was in the middle colonies — Maryland, Pennsylvania, New Jersey — that inoculation was most tolerated in the second half of the 18th century. That’s why Jefferson made the long journey to Philadelphia to be inoculated in 1766.

Jefferson first became aware of the discovery of a true smallpox vaccine from the newspapers he read in Philadelphia and the new capitol in Washington, D.C. Then, on Dec. 1, 1800, just after Jefferson’s election to the presidency, Benjamin Waterhouse sent him his pamphlet on the vaccine with a lovely cover letter saying that he regarded Jefferson as “one of our most distinguished patriots and philosophers.” Jefferson responded immediately, thanking Waterhouse for the publication and declaring, with his usual grace, that “every friend of humanity must look with pleasure on this discovery, by which one evil the [more] is withdrawn from the condition of man: and contemplating the possibility that future improvements & discoveries, may still more & more lessen the catalogue of evils. in this line of proceeding you deserve well of your [country?] and I pray you to accept my portion of the tribute due you.”

The following June, Waterhouse sent Jefferson a long letter explaining how the vaccine must be administered, how the serum could be preserved over time, and how much the controversial procedure needed the public support of a man of Jefferson’s stature in the “republic of letters.” President Jefferson became known as a defender and promoter of vaccination. In fact, he even arranged for his protégé Meriwether Lewis to carry some of the serum with him up the Missouri River in 1804-05, instructing him to “carry with you some matter of the kine pox, inform those of them with whom you may be, of its efficacy as a preservative from the small pox; and instruct & encourage them in the use of it. This may be especially done wherever you may winter.” Unfortunately, by the time the Lewis and Clark Expedition reached their winter encampment in today’s North Dakota, the serum had become inert. Thus Jefferson’s philanthropic initiative to vaccinate the Native Americans of the American West was stillborn.

Then, on May 14, 1806, now in his second term, Jefferson wrote perhaps the greatest presidential fan letter of all time. He took time from his duties as president to write the following letter to Edward Jenner. I quote it in its entirety:

SIR,— I have received a copy of the evidence at large respecting the discovery of the vaccine inoculation which you have been pleased to send me, and for which I return you my thanks. Having been among the early converts, in this part of the globe, to its efficiency, I took an early part in recommending it to my countrymen. I avail myself of this occasion of rendering you a portion of the tribute of gratitude due to you from the whole human family. Medicine has never before produced any single improvement of such utility. Harvey’s discovery of the circulation of the blood was a beautiful addition to our knowledge of the animal economy, but on a review of the practice of medicine before and since that epoch, I do not see any great amelioration which has been derived from that discovery. You have erased from the calendar of human afflictions one of its greatest. Yours is the comfortable reflection that mankind can never forget that you have lived. Future nations will know by history only that the loathsome small-pox has existed and by you has been extirpated. Accept my fervent wishes for your health and happiness and assurances of the greatest respect and consideration.

Who would not have wished to receive this magnificent, selfless, public-spirited, and enlightened letter? Unfortunately, we do not know how or even if Dr. Jenner responded. Except in medical circles, Edward Jenner has been largely forgotten.