When the opportunity presented itself to offer protection against smallpox by inoculation with smallpox material, a practice known as variolation, it was accepted in some European nations more successfully than in others. The procedure had been known elsewhere, including nasal insufflation, in which scabs from a mild case of smallpox were blown into the nostril. It had been practiced in ancient China as “planting of flowers,” and inoculation had been known in India “since before the Christian era” (19). The campaign to bring inoculation against smallpox to England was waged by Lady Mary Wortley Montagu (Fig. 1), who first encountered it while in Turkey with her husband, the British ambassador. Lady Montagu was an English aristocrat, beauty, and intellectual who jousted with no less a figure than Alexander Pope, the 18th-century poet. In 1717 she wrote to a friend that “the smallpox, so fatal, and so general amongst us, is here entirely harmless, by the invention of ingrafting which is the name they give it.” Lady Montagu described the procedure and quoted the French ambassador as saying that it is taken “by way of diversion.” She went on to say in part that “I am patriot enough to take pains to bring this useful invention into fashion in England . . . (19).” Strong willed and intelligent, Lady Montagu was highly motivated with respect to smallpox. She had lost her brother to smallpox, and her own attack of smallpox had taken her beauty, leaving her with a pockmarked face. She had her own children inoculated, and on her return to England the royal family took note. The successful inoculation of the two daughters of the Prince of Wales in 1722 “began the firm establishment of inoculation as acceptable medical practice in England” (19). However, there was early resistance to the practice in France, for example, where it was officially accepted finally in 1769.
Figure 1 Lady Mary Wortley Montagu. Lady Montagu, an aristocrat of considerable intellectual sophistication and beauty, brought the practice of variolation against smallpox to England from Turkey. It consisted of inoculating smallpox material and preceded Jenner’s discovery of vaccination, the inoculation of cowpox to prevent smallpox. Lady Montagu is shown in a Turkish embellished costume with a jeweled turban in an illustration from The Letters of Horace Walpole. (Courtesy of the James Smith Noel Collection, Louisiana State University, Shreveport, LA.)
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The risks and benefits of inoculation against smallpox and the attitude change in the population from resistance to acceptance were nicely documented by John B. Blake for colonial Boston (5). In the epidemic of 1721, theological and political considerations complicated the medical concerns. The death rate rose to 105 per 1,000, while that for the whole period from 1701 to 1774, including the epidemic, averaged 35 per 1,000. Inoculation was introduced in Boston in the 1721 outbreak by Zabdiel Boylston on the urging of Cotton Mather (19). Mather had learned of the practice in West Africa from his slave Onesimus. According to Blake, in the outbreak of 1729–1730 in Boston, of 2,600 persons with natural smallpox, 500 died (19%). In contrast, of 400 people inoculated, only 12 died (3%) (5).
The danger in variolation was the use of infectious “pus” taken directly from an individual with infected pustules or the use of ground, infected scabs. These materials were scratched into the skin of a healthy person in hopes of conferring resistance to disfiguring disease. Despite the marked reduction in mortality, there were several disadvantages attendant to inoculation. While less severe than natural smallpox, many experienced illness of various degrees of intensity, with some mortality. In addition, there was a costly preparation period of mercury and antimony administration. Even Edward Jenner experienced an arduous preparation period. Hence, the poor could not afford protection until 1764, when inoculation was first provided by the government (5). Most distressingly, inoculated persons were a source of virulent infection to their contacts. As a result, inoculation hospitals were necessary for supervision of administration. Blake notes that the experience of the American Revolutionary War resulted in greater acceptance of the practice. By tabulating deaths and cases from natural versus inoculated smallpox, Blake demonstrated a progressive acceptance of smallpox inoculation.
During the Revolutionary War smallpox played a devastating role, leading General George Washington to order the inoculation of the regular troops. In 1775–1776 the American attack on Quebec, to prevent its use as a British base, was thwarted by smallpox. As Hopkins put it, “But for the epidemic, the Continental troops would have captured the city, and hence, control of Canada” (see legend to Plate 31 in reference 19). In 1777 General Washington decided that the Continental Army needed to be inoculated to halt the spread of smallpox. “Should the disease rage with its usual virulence, we should have more to dread from it than the sword of the enemy . . .” (44). Various commentators have noted the crucial importance of Washington’s decision in the outcome of the war (49). Thus, adaptive immunity by variolation for protection against disease played a significant role in the history of American independence.
Hard on the heels of American independence came the description by Edward Jenner (Fig. 2) of vaccination against smallpox. At a stroke, it significantly reduced or eliminated the risks attendant to inoculation (variolation): illness and mortality and transmission of virulent disease to unfortunate and unsuspecting contacts. Jenner’s discovery was also revered in France. General Napoleon Bonaparte ordered the vaccination of his army soon after the turn of the 19th century. In fact, Jenner appealed to Napoleon for the pardon of an Englishman held in France. Considering the request, Napoleon was quoted as saying to the Empress Josephine, “What that man asks is not to be refused” (2).
Figure 2 Edward Jenner. Jenner was an English physician with an intense interest in natural science. He demonstrated the truth in the folk belief that previous infection with cowpox prevented smallpox. The description of the inoculation of a boy, James Phipps, with material from a sore on the hand of a dairymaid, Sara Nelms, has achieved iconic status. Jenner published his results of vaccination in 1798. Vaccination eliminated the scourge of smallpox through the WHO Global Eradication Programme by 1979. (Courtesy of the National Library of Medicine.)
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Inoculation with smallpox, or variolation, was to provide an essential link in the later demonstration of the protective action of cowpox against smallpox infection. Edward Jenner was ideally prepared to be the vehicle of that demonstration. He had had first-hand experience with smallpox inoculation as a child of 8 years of age. He had undergone extensive preparation by purging and bleeding before inoculation (2). As an apprentice in surgery and pharmacy, he had learned of the folk knowledge that exposure to cowpox prevented infection with smallpox. As a medical practitioner, he apparently was an inoculator. Interestingly in light of the later