Smallpox was once a terrible and deadly disease. It affected communities across the globe, but when Jefferson was alive there were known ways to combat it. For today's episode, we track the course of smallpox and the development of inoculation in early American history.

Kyle Chattleton: This is Mountaintop History, a podcast produced by the Thomas Jefferson Foundation at Monticello. 

Olivia Brown: Mountaintop History brings forward meaningful stories from this historic home and plantation — from the past and from the present.  

Kyle Chattleton: My name is Kyle Chattleton. 

Olivia Brown: And I'm Olivia Brown. 

Kyle Chattleton: Thank you for joining us. We hope you'll learn something new. 


Since December 2019, when Chinese government officials announced the discovery of a troubling disease, the global community has been grappling with COVID-19, a virus that has brought untold hardship, acute and lasting sickness, and death to so many. Vaccines have limited the pandemic’s impact, and new technologies are a positive sign for humanity. 

History can provide a lesson here: COVID-19 is not the first deadly disease to cross the globe, nor is it the first to provide an environment for advances in medicine.

Before he was President, before he wrote the Declaration of Independence, before the American Revolution, Thomas Jefferson feared an invisible enemy. In 1766 and at the age of 23, Jefferson was traveling in the hope he could protect himself from smallpox, one of the deadliest diseases in human history. As ever, though, politics were on his mind: “I would give you an account of the rejoicings here on the repeal of the stamp act,” Jefferson wrote to his friend John Page, “but this you will probably see in print before my letter can reach you. I shall proceed tomorrow to Philadelphia where I shall make the stay necessary for inoculation.”

Smallpox was an infectious disease caused by the variola virus. While it is unknown exactly where and when the virus first made contact with humans, evidence of the disease can be found in Egypt 3,000 years ago. Smallpox slowly spread across the globe: it was documented in 4th century China, reached Northern Africa and Western Europe 300 years later, and through European colonization arrived in North America starting in the 1500s. The disease came with terrible symptoms: fever, vomiting, and the creation of multiple blisters and scars across the body that gave “smallpox” its name. For every 10 people who contracted smallpox, roughly 3 died from it, but death was not shared equally: the virus ultimately devastated the Indigenous peoples of North America.

When Jefferson was heading to Philadelphia in 1766, however, there were known ways to combat the disease. Inoculation, or variolation, was a procedure that had spread from West Africa to the British Colonies by way of an enslaved man called Onesimus. He educated his enslaver, Cotton Mather, about a technique where active smallpox from a sore is transferred to an uninfected person, either by having them inhale the material or placing it in a cut in their arm.

This was the procedure that Jefferson underwent. After the person was given the smallpox virus, they usually developed mild symptoms. There was, however, still a risk of serious infection and even death. As part of the procedure, Jefferson would have quarantined himself to prevent spreading the disease. To let others know to stay away, inoculated people raised a flag over their homes. And after the symptoms had subsided, the inoculated person was now immune to smallpox.

Jefferson was successfully inoculated in 1766. But Onesimus taught Cotton Mather about inoculation decades earlier. Both were living in Boston, and in 1721 there was an outbreak of smallpox in the city. Mather convinced a local doctor to use the method on citizens to great effect.

Not everyone saw it as a positive development, and fear over the procedure began to spread. The New-England Courant, a Boston newspaper published by James and Benjamin Franklin, became a forum for inoculation detractors during the smallpox outbreak. They published a piece by John Williams in which he argued that inoculation went against natural and divine laws. Someone ultimately threw a homemade bomb into Mather’s home, attaching to it a message: “COTTON MATHER, You Dog, Dam you. I’l inoculation you with this, with a pox to you.” The bomb failed to detonate. Privately, Mather wrote, “Warnings are to be given unto the wicked Printer, and his Accomplices, who every week publish a Vile paper. […] A Wickedness never parallel’d any where upon the Face [of] the Earth.”

One of those printers, Benjamin Franklin, later expressed regret. In his Autobiography, he wrote:

“In 1736 I lost one of my sons, a fine boy of four years old, by the small-pox, 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 parents who omit that operation, on the supposition that they should never forgive themselves if a child died under it.”

Smallpox proved a challenge during the Revolutionary War. Jefferson lamented “the ravages of the small pox with which one half of our army is still down.” George Washington ultimately forced all of his soldiers to be inoculated to prevent the disease from claiming more victims among the troops.

There were also problems with the plague on the other side of the battlefield. Many enslaved people, including some of those Jefferson held in bondage, made a bid for freedom and escaped to fight on the side of the British. Arriving behind British lines, they lived in encampments similar to those of most armies: close quarters with limited sanitation. The virus spread easily and many died from smallpox. An enslaved man from Monticello, Isaac Granger Jefferson, later reminisced about what he saw in the British camps: “It was very sickly […] great many colored people died there.”

Isaac Granger Jefferson was likely among the 200 or so people Thomas Jefferson later had inoculated at his Monticello plantation and the nearby community in 1801. As the then-President of the United States, Jefferson was openly supporting a new medical procedure developed by Edward Jenner. Jenner had discovered that the milder cowpox virus proved to be a powerful vaccine against smallpox. Jefferson wrote with hope:

“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 of future improvements & discoveries, may still more & more lessen the catalogue of evils.”

280 years after Jefferson wrote those words, the World Health Organization declared that smallpox had been completely eradicated. In the midst of the COVID-19 pandemic, scientists now believe that new vaccine technologies could potentially lead to more powerful treatments for cancer, cystic fibrosis, influenza, and HIV. Jefferson expressed hope about this world of tomorrow when he stated, “I like the dreams of the future better than the history of the past.”


Olivia Brown: This has been another episode of Mountaintop History, a collaboration podcast between WTJU and the Thomas Jefferson Foundation. 

Kyle Chattleton: Join us for new episodes every two weeks on Apple and Google Podcasts, Stitcher, and the Virginia Audio Collective. 

Olivia Brown: To learn more about Monticello or to plan your next trip, visit us online at