rel="nofollow" href="#ulink_8c3c6107-2e1e-5b79-8960-a4b930c28267">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.)
doi:10.1128/9781555818586.ch3.f2
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 use of cowpox to prevent smallpox, he inoculated his young son with swinepox in 1789. A few years later, he inoculated his son with smallpox, which failed to take, implying protection against smallpox (43) conferred by the earlier treatment.
Jenner’s powers of observation as a naturalist were strong; he was elected to the Royal Society based on observations on the nesting behavior of the cuckoo. Those talents are on display in his self-published pamphlet on cowpox in 1798 (21). Jenner noted that “. . . but what renders the Cow-pox virus so extremely singular, is that the person who has been affected is for ever after secure from the infection of the Smallpox; neither exposure to the various effluvia, nor insertion of the matter into the skin, producing the distemper.” Jenner’s Case I was Joseph Merret, who had tended horses with sore heels, an infectious disease called “the grease.” Merret developed sores on his hands and swelling and stiffness in his axillae. It was Jenner’s belief that the grease was transmitted by farm workers to cows which then transmitted cowpox to milkers, thereby protecting them from smallpox. Twenty-five years later, Merret was inoculated with “variolous matter,” but it did not take. Jenner noted that since the population was thin and any case of smallpox recorded, it was certain that Merret had not had smallpox in the intervening years. Apparently the relationship between the grease and cowpox was discredited (35). However, the link between cowpox and immunity to smallpox was sustained. Then came what history has recorded as the decisive event.
Jenner attempted artificial infection by cowpox of a boy, James Phipps, with matter taken from a sore on the hand of a dairymaid, Sarah Nelms, who had been infected by her master’s cows. Lesions of the incisions “were much the same as when produced in a similar manner by variolous matter,” and a week after inoculation he had a brief episode of axillary discomfort and systemic symptoms. The crucial test came on 1 July following when he was inoculated with variolous matter: “No disease followed.” Several months later he was again challenged with variolous matter, “but no sensible effect was produced on the constitution” (7). Phipps was the same age, 8 years, as Jenner had been when Jenner experienced the arduous preparation for variolation (2).
It is a paradox that this first experimental observation of what was the most beneficial medical public health intervention ever devised was first rejected by the Royal Society in 1797. Hopkins has aptly put it, “Because his evidence was so slim and his conclusion so audacious, the paper was quietly returned . . .” (19). Despite resistance among some (Fig. 3), the value of vaccination was very promptly recognized and vaccination was taken up by others. In just a decade after James Phipps was vaccinated, Thomas Jefferson was able to write to Edward Jenner in 1806, “Further generations will know by history only that the loathsome smallpox has existed” (19). It is an extraordinary achievement that came to pass. In 1966 the WHO undertook the Global Eradication Programme to rid the world of smallpox, which was accomplished and certified in 1979, closing
