As the First Smallpox Vaccine Turns 224, A Look at How It Started

george washington and memory cells also figure into the fight against smallpox

By Jonny Lupsha, Wondrium Staff Writer

According to The History of Vaccines, the first smallpox vaccine was tested on May 14, 1796, by Edward Jenner. He inoculated a child with material from a sore caused by cowpox in order to test a theory that it would give protection from the smallpox disease. Protecting against the illness has a fascinating history.

Smallpox vaccine concept
The eradication of smallpox was due to the innovative contribution of Edward Jenner and subsequent efforts of developing immunization against the disease. Photo by OneSideProFoto / Shutterstock

The website The History of Vaccines said that the first smallpox inoculation came about as a test of a hypothesis that a cowpox infection could protect someone from getting the smallpox disease. “On May 14, 1796, [Edward] Jenner inoculated eight-year-old James Phipps with matter from a cowpox sore on the hand of milkmaid Sarah Nelmes,” the website said. “Phipps suffered a local reaction and felt poorly for several days but made a full recovery. In July 1796, Jenner inoculated Phipps with matter taken from a fresh human smallpox sore, as if he were variolating the boy, in an attempt to challenge the protection from cowpox. Phipps remained healthy.”

The 18th-century history of inoculating against smallpox also includes a young George Washington.

Saving Soldiers

In 1776, the colonies that would become the United States of America faced an enemy that George Washington considered to be more dangerous than the British army.

“Smallpox had ravaged General Horatio Gates’s American Northern Army,” said Dr. David Sadava, Adjunct Professor of Cancer Cell Biology at the City of Hope Medical Center. “Of 10,000 troops, over half of them got smallpox, and the military campaign had to be suspended for a month.”

Dr. Sadava said that Washington spoke of smallpox from experience. In his teenage years, Washington took his half-brother Lawrence to Barbados to help with Lawrence’s tuberculosis. Although the trip failed to help Lawrence, George contracted smallpox and learned of its dangers. By the time of the Revolutionary War, he had come to appreciate how serious smallpox could be. He chose to order his troops to be inoculated against the illness the following year.

“The 1777, inoculation ordered by Washington was the first-known inoculation of an army, and it worked pretty well,” Dr. Sadava said. “Casualties to smallpox were greatly reduced and history tells us that the colonists, of course, won the Revolutionary War.”

Smallpox and the Immune System

George Washington contracted smallpox when he was a teenager, but he obviously lived for a long time afterward due to his body’s vigilant immune system.

“Washington’s immune system, the system that fights disease, fought off the infection in several steps,” Dr. Sadava said. “After the smallpox virus entered Washington’s body, some white blood cells called phagocytes engulfed the virus. They digested it to small pieces, chopped it up, and they presented some of these protein fragments of the virus on their cell surface.”

After this, Dr. Sadava said, other white blood cells flagged the smallpox virus and set a series of events in motion that saved Washington’s life. These events included sending cells called killer T-cells into the fight which targeted any cell in Washington’s body that carried smallpox.

“Still other white blood cells, called B-cells, made antibodies—these are blood proteins that would bind up any viruses that were outside Washington’s cells, that hadn’t infected a cell but were in the bloodstream, for example,” Dr. Sadava said. “So these B-cells made a whole army that would make antibodies that would bind them up. This two-pronged attack—cells to kill infected tissue and antibodies to bind up free viruses—swiftly reduced the infection to a mild one in Washington’s case.”

Dr. Sadava said that once smallpox was eradicated from Washington’s body, the remaining cells that stood guard to watch for smallpox were called memory cells, and they were the same types of cells that were key to inoculating the army. He said that when dead smallpox viruses from the pus of smallpox victims was put into the cut skin of Continental Army soldiers, the viruses looked enough like their live counterparts to spur the immune system into producing the T- and B-cells required to fight the virus.

Today, smallpox has mostly been eradicated through vaccination. It wouldn’t have been possible without Edward Jenner’s cowpox experiment and George Washington’s caution over the disease.

Dr. David Sadava, Ph.D.

Dr. David Sadava contributed to this article. Dr. Sadava is Adjunct Professor of Cancer Cell Biology at the City of Hope Medical Center and the Pritzker Family Foundation Professor of Biology, Emeritus, at The Claremont Colleges. He earned a B.S. with first-class honors in biology and chemistry from Carleton University and a Ph.D. in Biology from the University of California, San Diego.