Hektoen International

A Journal of Medical Humanities

Edward Jenner (1749-1823): from variolation to vaccination

Damiano Rondelli
Chicago, Illinois, United States


Figure 1. Portrait of Edward Jenner

Smallpox virus is a linear double stranded DNA virus that belongs to the family of poxviridae. Because  its surface is covered with filamentous proteins, it has the appearance of a wool knitting ball. Dr. Edward Jenner’s observations on immune protection from smallpox at the end of the eighteenth century were a milestone in the history of medicine and of humanity itself. Yet at the time of his discovery he faced objections and mistrust.


Smallpox before Jenner

Since 570 A.D. the disease has been  called variola – from the Latin varius (stained) or varus (mark on the skin). The English word smallpox originated from “small poke” (small sacs) as opposed to the “great poke”, syphilis.

The initial decline of the Roman Empire coincided with a large epidemic at the beginning of the second century, known as the Antonine Plague, which caused the death of several millions. In 1518, following the arrival of Spanish conquistadores on the island of Hispaniola, an outbreak of smallpox, until the unknown in the New World, decimated the population. From there the disease spread rapidly throughout the Americas, exterminating most of the Aztecs and Incas. Within a century the population of Mexico fell from about 25 million to 1.6 million. In the eighteenth century some 400 thousand people died each year from smallpox and one third of the survivors were left blind. At the end of the 1700s the case-fatality in infants approached 80% in London and 98% in Berlin.

The practice of inoculation (or variolation) had been followed for centuries in Africa, India, and China. It consisted of the subcutaneous instillation of smallpox virus (from the pustules of patients) into non-immune individuals who would then have had a chance to become resistant to subsequent infection. Avicenna (980-1037), the famous Arabic doctor who preserved the knowledge of the Hippocratic and Galenic medicine in the MiddleAges, proposed to inoculate smallpox material either through the skin or by inhalation. The active trade routes throughout Asia spread the knowledge of variolation within the Ottoman Empire, where women recruited from Caucasian villages to become spouses of the Sultan likely promoted this practice. In Europe it was only at the beginning of the eighteenth century that doctors familiar with these exotic traditions were asked to help, at first only members of the royal family. Because of controversial discussions, an experiment was also run on six prisoners in London. Throughout the eighteenth century the practice of variolation became more diffuse in Europe. It decreased mortality but  itself had a 2-3 percent mortality of variolated people who would develop smallpox itself. Variolation reached also the New World in 1721 with Rev. Cotton Mather and Dr. Zabdiel Boylston in Boston. By 1777 all the soldiers of George Washington had been variolated.


Figure 2. The hand of Sarah Nelms from Jenner’s book: An Inquiry of the causes and Effects of the VariolæVaccinæ(1798)

Edward Jenner

In 1757, an eight-year old boy in Gloucester (UK) was inoculated with smallpox and became immune. His name was Edward Jenner. Son of the Rev. Stephen Jenner, he lost his father at the age of five and went to live with his older brother. At thirteen he was apprenticed to a country surgeon. There he heard for the first time that dairymaids were in some way protected from smallpox. This had been a common observation in rural medicine but had not prompted any further investigation. Jenner (Figure 1) went to London and studied with the famous surgeon John Hunter at St. George’s Hospital.

Jenner’s scientific interests expanded beyond medicine to natural science, biology, and hydrogen balloons, but the observation that dairymaids in contact with cowpox were protected from smallpox became a scientific hypothesis to be tested. In May 1796, Jenner took material from the hand of the young dairymaid Sarah Nelms (Figure 2), who had cowpox lesions, and inoculated the eight year old boy James Phipps. The boy developed a mild fever and lost his appetite on the ninth day, but the next day he felt better. In July of the same year, Jenner inoculated the boy with material from a fresh smallpox lesion (Figure 3) and the child did not develop the disease. Jenner concluded that the protection was complete.

In 1797, Jenner sent a short communication as a case report to the Royal Society of Medicine describing his method and results, but his paper was rejected. In 1798 he added a few cases and privately published a booklet in London entitled: “An Inquiry into the Causes and Effects of the VariolæVaccinæ, a Disease Discovered in Some of the Western Counties of England… Known by the Name of the Cow Pox “. This little book changed the history of medicine. Since the name for cow in Latin is vacca, and cowpox is vaccinia, Jenner decided to call this procedure vaccination.

Figure 3. Jenner vaccinating James Phipps. Painting by Ernest Board (early 20th century).

Jenner’s publication was not immediately appreciated and for three months he found no volunteers in London. Only in 1799 did other doctors begin to use his vaccination, and Jenner conducted a nationwide survey to prove resistance to smallpox among people who had cowpox. Gradually vaccination replaced variolation, which in England was prohibited in 1840. Jenner’s discovery was replicated in other European countries and his book translated in many languages. Edward Jenner finally obtained the credit that he deserved. He then retired from public life and went back to practice country medicine. Between 1810-1815 his wife, one son, and two sisters died of tuberculosis. On January 23, 1823, he visited his last patient. The next day he had a stroke and died on January 26.


The end of smallpox

In the nineteenth century the death rate from smallpox declined and it was determined that subsequent re-vaccination was necessary. Smallpox was eradicated in Europe and North America in 1950s, but not in Asia. In 1967 the World Health Organization launched a campaign to eradicate smallpox globally and this campaign successfully ended in 1977. On May 8, 1980, the World Health Assembly announced that the world was free of smallpox.



  1. Crosby A. in Plague, Pox & Pestilence – Disease in History, editor: KF Kiple, London 1997, p.74-79
  2. Riedel S. Edward Jenner and the history of smallpox and vaccination.Proc (BaylUniv Med Cent). 2005 Jan; 18(1): 21–25.
  3. Rondelli D. Storiadelle Discipline Mediche, Hippocrates Edizioni Medico-Scientifiche, Milano2004, p. 3779-380



DAMIANO RONDELLI, MD, is the Michael Reese Professor of Hematology, Chief of the Division of Hematology/Oncology and Director of the Blood and Marrow Transplant at the University of Illinois Hospital & Health Sciences System, Chicago, IL. He initially completed his medical school and fellowship in hematology, and then started his academic career at the University of Bologna, Italy. He joined the University of Illinois at Chicago in 2002. His research interests are both in preclinical models and clinical trials in stem cell transplantation. He is the author of over 100 scientific peer-reviewed articles, multiple book chapters, and is the editor of the book, Storia delle Discipline Mediche [History of Medical Disciplines], Edizioni Hippocrates, Milano 1999 and 2003. He is the Chair of the Chicago chapter of ISSNAF (Italian Scholars and Scientists of North America Foundation) and a fellow of the Institute of Medicine of Chicago (IOMC).


Spring 2016  |  Sections  |  Infectious Diseases

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