First Widespread Smallpox Inoculations

Locale China, Eastern Europe, Ottoman Empire, and Africa

Date c. 1670

Techniques of inoculation, or “variolation,” against smallpox, which had long been practiced in China, were further developed and widely used there in the seventeenth century. The spread of these techniques throughout the world, especially to the Turkish Ottoman Empire, eventually took them to Great Britain in the early eighteenth century and resulted in the first modern vaccination techniques.

Key Figures

• Li Shizhen (Li Shih-chen; 1518-1593), Chinese scientist and writer
• You Chang (Yu Ch’ang; fl. mid-seventeenth century), Chinese medical writer
• Mehmed IV Avci (1642-1693), sultan of the Ottoman Empire, r. 1648-1687

Summary of Event

The origins of the types of smallpox inoculations that found widespread application in seventeenth century China can be traced to the tenth century, when Song DynastyPrime Minister Wang Dan’s oldest son died of smallpox, and he called on medical experts, scholars, scientists, and sorcerers to find a way to protect his remaining family members. In response, a Daoist hermit who practiced alchemy reportedly revealed the secret of smallpox inoculation, which some sources claim may have been in existence since the sixth century in China. However, the procedure was not commonly performed for more than five hundred years. A 1596 book on botany and medicine by Li Shizhen contains the earliest known published description of the procedure.

Seventeenth century Chinese writers reported that general knowledge and the common application of smallpox inoculation did not occur until the period 1567-1572. You Chang’s Wen yuan ge shou chao ben (1643; miscellaneous ideas in medicine; reprinted as Yu yi cao, 1971; tales of herbs) gave a detailed description of the procedure, which basically consisted of introducing dried smallpox scabs into the body through inhalation or on a cotton plug that was inserted in the nose. By the seventeenth century, the potential danger of “variolation,” which stemmed from introducing the live smallpox virus, rather than dead or weakened versions, had been significantly reduced by refining the procedure—an impressive feat, given that these refinements had to be achieved at a time when viruses had not yet been discovered.

Despite their ignorance of viruses per se, Chinese medical authorities understood that the smallpox scabs used for inoculations had to be weakened, or attenuated, in order to avoid transmitting the full-blown disease, and guidelines for safe variolation were established. They knew the difference between Variola major, the most deadly form of the disease, and Variola minor, the less virulent type. Scabs were to come from Variola minor, and no unattenuated scabs were to be used. Scabs from patients who had themselves been inoculated and developed a mild infection were preferred. The procedure was made even safer by using scabs produced through several generations of inoculations, that is, scabs from a patient who had been variolated with scabs from an earlier variolation, and so forth, for a number of generations.

Methods for artificially weakening the virus even further were also developed. Scabs were aged for a month or so in a sealed bottle, which reduced their potency. If supplies of new scabs were limited, older scabs were combined with the newer ones to produce an attenuated powder. It is now known that these attenuation procedures killed 80 percent of the viruses used for inoculations. They greatly reduced the chance of transmitting smallpox while still generating sufficient antibodies to protect against the disease. The inoculations also strengthened the immune system by stimulating the body’s production of a substance called interferon. The end result was a relatively safe and effective method of creating a lifetime immunity to a long-dreaded disease. The Chinese also developed an oral vaccine in the 1600’, with some claimed success. Healthy people who took pills that were made from the fleas found on cows reportedly were protected from smallpox, to some extent.

Variolation migrated from China to the Middle East and was actively promoted by traders who claimed that it had protected them and, in some cases, their human cargo. The Middle Eastern version of the procedure involved recovering fluid from the pustules of someone with a mild case of smallpox and introducing it into a superficial puncture or scratches, usually on the patient’s arm. Caravans from the Circassian region (the Republics of Adygea, Karachay-Cherkessia, and Kabardino-Balkaria, located in the Caucasus) introduced variolation to the Ottoman Empire in 1670. Sultan Mehmed IV Avci preferred the reputedly beautiful women of the Caucasus for his harem in the court of the Sublime Porte in Istanbul and had many imported. These women, who were inoculated as children in parts of their bodies where the scars could not be seen, disseminated information on variolation to the court. The practice became relatively widespread when it was found that between 1-3 percent of inoculated patients died, compared to 30 percent or more of the people who contracted smallpox naturally.

Variolation for smallpox also found its way to Africa in the seventeenth century. Crude inoculation practices may have existed in Africa for hundreds of years prior to the 1600’, but there is evidence that variolation procedures similar to those in the Ottoman Empire were used in seventeenth century Africa. The most common African procedure was only a slight variation on the Middle Eastern version: Fluid from smallpox pustules was deposited into a shallow cut, usually on the patient’s leg or arm, rather than into a puncture or scratches.

The practice of variolation migrated from Africa to colonial America through the slave trade. Onesimus, a slave who was a servant to the Reverend Cotton Mather of Boston, Massachusetts, had been variolated in Africa as a child in the seventeenth century. In 1706, he explained the procedure to his master, and Mather became a strong advocate of its use. Initially, however, he found only one doctor who was willing to inoculate a small number of patients, and the procedure remained very controversial for decades, severely limiting its application in the American colonies.

Significance

Crude smallpox variolation techniques had been practiced in various parts of the world for hundreds of years prior to the seventeenth century. However, the refinement of inoculation technology in late sixteenth century China made the procedure safer and more effective, leading to its widespread use throughout the seventeenth century, which saved millions of lives in China and in the other regions to which it was exported.

The introduction of this procedure to England in the following century began a series of events that dramatically altered the course of history. Lady Mary Wortley Montague, who lived in Turkey between 1716 and 1718, learned about variolation there and had her five-year-old son inoculated. Upon returning to England, she had her four-year-old daughter variolated before the most prominent physicians in the country. The procedure soon became widespread when trials showed that most who were inoculated did not become ill when exposed to smallpox.

This “Turkish method” of inoculation did pose some risk, because it used material from smallpox sufferers (the term “variolation” comes from “variola,” the technical term for smallpox). In 1796, British physicianEdward Jenner discovered that inoculation with fluid from the sores of people with cowpox, which was related to smallpox but was not lethal, would provide immunity from smallpox. This procedure was called “vaccination,” from vacca, which means cow. Like the seventeenth century Chinese, Jenner used the fluid from the sores of patients who had been vaccinated earlier to ensure quality control, and the end result was similar: the development of immunity and the production of interferon. By the mid-nineteenth century, the British government had outlawed variolation and made vaccination mandatory in order to control smallpox. Jenner’s breakthrough is credited not only with the global eradication of smallpox by 1980 but also with the creation of the science of immunology, which has produced numerous vaccines against crippling and lethal diseases and holds promise for the control of others.

Bibliography

Barquet, Nicolau, and Pere Domingo. “Smallpox: The Triumph over the Most Terrible of Ministers of Death.” Annals of Internal Medicine 127 (1997): 635-742. A comprehensive history of the global spread of smallpox, the resulting epidemics, and early Chinese inoculation practices that eventually led to modern vaccination techniques.

Baxby, Derrick. “The End of Smallpox.” History Today 49, no. 3 (March, 1999): 14-16. Explains how high seventeenth century smallpox mortality rates in England and inoculation techniques from the East gave rise to vaccinations, which were made compulsory.

Plotkin, Susan L., and Stanley A. Plotkin. “A Short History of Vaccination.” In Vaccines, edited by Stanley A. Plotkin and Walter A. Orenstein. 4th ed. Philadelphia: Saunders, 2004. Includes discussions of various types of smallpox inoculation techniques in seventeenth century China, their migration to England via the Ottoman Empire, and the modern vaccination techniques that resulted.

Vetter, Richard, and Donna Hoel. “Vaccines and the Power of Immunity.” Postgraduate Medicine 101 (1997): 154-159. A concise history of smallpox inoculation techniques, their spread to colonial America and Great Britain, and the resulting development of the contemporary science of immunology.