The Greek historian, Thucydides, discovered twenty four centuries ago that smallpox survivors were resistant to subsequent smallpox episodes. Thucydides’ remarkable perception, more than two thousand years before awareness of infectious agents, may have influenced his fellow Athenians, since those who survived the infection comprised the few who were willing to care for those who fell ill. Thucydides’ insight was lost to Western medicine. However, the independent perception in China, that that smallpox survivors are entirely safe from a second attack, led to the development there, about 1,000 years ago, of an empirically based smallpox control strategy, in which uninfected individuals were protected by inhaling powder prepared from dried smallpox scabs. The scabs were from individuals who survived a mild smallpox infection. They were dried to further diminish the likelihood of the recipient undergoing a severe infection.
By 1700, the process had spread to Africa, India, Arabia, and the Ottoman Empire. The Arabians streamlined this approach by transferring the dried postular material on the point of a needle. Lady Mary Wortley Montague, the wife of the British ambassador to Turkey, had her children undergo the process in the early 18th century, and then brought the practice to Europe, where British physicians dubbed it “variolation.” [See Cotton Mather, Onesimus, George Washington, and Variolation, posted on the blog November 20, 2013, for an account of the introduction of variolation to the New World.]
As might be expected, variolation carried risks that would not be acceptable today. However, those risks were tolerable in 18th century Europe, when as many as one person in ten died of smallpox. We now have the smallpox vaccine, which was the first, and arguably the most successful vaccine ever put into practice. Remarkably, the smallpox vaccine was developed in 1798 by an English country doctor, Edward Jenner, a half-century before the germ theory of disease, and 100 years before the actual discovery of viruses!
At thirteen years of age, Jenner was apprenticed to an English surgeon; a mister Ludlow. While Jenner was in Ludlow’s service, he heard the doctor suggest to an ill milkmaid that she might be coming down with smallpox. The milkmaid replied that she could not get smallpox since she already had cowpox. The notion, that having had cowpox protects one against smallpox, may actually have been common among English country folk of the day, but it was just as commonly dismissed by physicians.
At 21 years of age, Jenner continued his training under the prominent British surgeon, John Hunter. When Jenner ran the milkmaid’s comment by Hunter, the great surgeon encouraged his young protégé to investigate the matter further.
Now, perhaps the most remarkable part of the story. History usually credits young James Phipps as the first person “vaccinated” by Jenner. And, while Phipps, in 1796, was the first individual Jenner inoculated with cowpox, and subsequently challenged with smallpox, he was, in fact, not the subject of Jenner’s first experiment. Instead, that person was Jenner’s first son, Edward, Jr., born in 1789. Jenner inoculated Edward Jr. with swinepox when the infant was only 10 months old!
Jenner could not have known about microbes, and he left no records revealing his purpose in inoculating Edward Jr. with swinepox. It may be relevant that cowpox was relatively rare at the time, while a similar pox disease was more common in pigs. Regardless, Jenner’s baby son became sick on the eighth day with a pox disease, from which he fortunately recovered. Then, his father proceeded to challenge him with genuine smallpox!
Fortunately, Edward Jr. also resisted his father’s experimental attempt to transmit smallpox to him. His father tried again in 1791, when the boy was two, and again when he was three. Edward Jr. resisted each of Edward Senior’s smallpox challenges, most likely because the swinepox virus immunized him against smallpox. We can only guess how Mrs. Jenner regarded these happenings.
Jenner also used several other young children in his experiments, including his 11-month-old second son, Robert. One of these children died from a fever, possibly from a contaminant (streptococcus?) in the vaccine. In those days one could hardly know what might be in a vaccine.
In Jenner’s famous and classic experiment involving James Phipps, he used a lance to pierce a cowpox postule on the wrist of a young milkmaid, Sarah Nelmes. He then scratched James twice on the arm with the lance. Six weeks afterwards, Jenner challenged James with smallpox from a postule on the body of a smallpox patient. The smallpox challenge caused only a slight inflammation on James’ arm, indicating what now would be recognized as an immune reaction. During the next 25 years or so, Jenner challenged James twenty more times with smallpox, with never any sign of the disease.
Not much else is known about James Phipps, who was only 8 years old when he was first inoculated by Jenner. Additionally, nothing is known about James’ parents and whether they may have consented to Jenner’s use of James. However, Jenner referred to his young subject as “poor James,” and looked after him in later years, suggesting he may have felt some remorse. Moreover, he eventually built a cottage for James and even planted flowers in front of it himself. Little is known of Sarah Nelmes.
Thankfully, the sorts of experiments Jenner carried out cannot be done today. Yet because of his efforts, the once dreaded smallpox virus now exists only in the laboratory.
More than a century would have to pass before it could be appreciated that the protection against smallpox that was generated by inoculation with cowpox and swinepox depended on the facts that these two viruses are immunologically cross-reactive with smallpox virus and that they produce a relatively benign infection in humans. [When contemporary vaccinologists develop vaccines to protect against viral diseases, they are essentially tapping into biological mechanisms that have been perfected through eons of natural selection. Indeed, the principal fact exploited by vaccinologists is that natural infection, by many different viruses, results in lifelong immunity against the same virus.]
Some final points:
It is possible that Jenner was not the first to use cowpox to vaccinate against smallpox. However, he was the first to eliminate the cow from the procedure. That is, he transmitted immunity from person-to-person, without the need for an infected cow. Nevertheless, he hung in his house the hide of the cow, which had initially given Sarah Nelmes cowpox.
Although Jenner demonstrated that his vaccine could be passed indefinitely from person-to-person, neither he, nor anyone else at the time, had the insight that this indefinite passage meant that the active agent in the vaccine must be able to replicate.
Greer Williams: Virus Hunters, Alfred A. Knopf, 1960.
Cotton Mather, Onesimus, George Washington, and Variolation, posted on the blog November 20, 2013.
Smallpox in the New World: Vignettes featuring Hernan Cortes, Francisco Pizarro, and Lord Jeffry Amherst, posted on the blog February 24, 2014.
Notable Individuals Who Survived Smallpox and One Who Didn’t: Featuring Abraham Lincoln, Elizabeth I, Josef Stalin, and Pocahontas, posted on the blog March 10, 2014.