Читать книгу To Catch a Virus - John Booss - Страница 28

The role of recovery from a first episode of an infectious disease in providing protection against another attack has been known for centuries. Characteristic traces of smallpox, pockmarks on the skin, were recognized as evidence of past infection and hallmarks of immunity to reinfection. Acute smallpox infection had to be distinguished from other viral exanthema such as measles. Rhazes, a Persian physician of the 10th century in Baghdad, wrote A Treatise on the Smallpox and Measles, which is regarded as a landmark in clinical description (34). Rhazes reported the symptoms that may precede the skin eruptions: “. . . a continued fever, pain in the back, itching in the nose, and terrors in sleep.” The authority of this treatise in Europe extended into the 17th century.

Two millennia before Rhazes, Ramses V died in 1157 BCE of what was assumed to be smallpox, and his body was mummified. Donald R. Hopkins recounts a remarkable episode in which he was granted permission by Egyptian president Anwar el Sadat to examine the front upper half of the unwrapped mummy in 1979 (19). After describing the rash of elevated “pustules,” Hopkins concluded that the appearance and distribution were “similar to smallpox rashes I have seen in more recent victims.” Hopkins, a physician who participated in the WHO Smallpox Global Eradication Programme, also wrote the classic treatise on the history of smallpox, Princes and Paupers. It was first published in 1983 and republished in 2002 with a new introduction as The Greatest Killer. While the exact origins of smallpox cannot be documented with certainty, it has been assumed that it arose millennia ago when aggregations of populations in towns and small cities emerged that supported epidemic spread.

The terror and dread occasioned by smallpox were well captured by the British historian Thomas Babington Macaulay in his History of England: “. . . the smallpox was always present, filling the churchyards with corpses, tormenting with constant fears all whom it had not yet stricken, leaving on those whose lives it spared the hideous traces of its power, turning the babe into a changeling at which the mother shuddered, and making the eyes and cheeks of the betrothed maiden objects of horror to the lover” (quoted in reference 10). Macaulay’s characterization of “all whom it had not yet stricken” is an implicit statement of the immunological protection of those “whose lives it spared.”

In contrast to lands where “the smallpox was always present,” populations in which smallpox had not previously existed were devastated on its first appearance. Nowhere, perhaps, is this more stunning and graphically illustrated than with its introduction into the western hemisphere—so stunning, in fact, that the American historian William McNeill began his seminal Plagues and Peoples asking how Hernando Cortez, with fewer than 600 soldiers, was able to conquer the Aztec empire of Mexico with its millions of inhabitants and later how Pizarro was able to conquer the Inca empire in South America (25). The scourge of smallpox nearly wiped out the previously unexposed Aztec and Inca populations, allowing Cortez easy victory over his diminished opposition. McNeill implicitly notes the role of immunological protection in that the Spaniards had the advantage of previous exposure to smallpox, whereas the Amerindians had not. He writes that smallpox was “. . . . a disease that killed only Indians and left Spaniards unharmed.” McNeill comments, “the lopsided impact of infectious disease upon Amerindian populations therefore offered a key to understanding the ease of the Spanish conquest of America—not only militarily but culturally as well.” Elsewhere on the North American continent, Francis Parkman wrote of a smallpox outbreak among the Huron Indians north of Lake Ontario in 1636: “Terror was universal . . . its ravages were appalling. . . . No house was left unvisited. . . . Everywhere was heard the wail of the sick and dying children” (quoted in reference 11). European history was also significantly influenced by smallpox: McNeill documents that smallpox altered the course of British political history. Hopkins termed the killing of kings, queens, an emperor, and a tsar in or around the 18th century “. . . a regicidal rampage without parallel . . .” (19). Thus, whole populations were devastated by smallpox in the New World, and leadership as well as the common people was destroyed in the Old World.

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 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 the magnificent chapter in smallpox history. Further accounts of this momentous accomplishment are detailed in “the big red book,” Smallpox and Its Eradication (13).

Figure 3 Triomphe de la Petite Vérole (Triumph of Smallpox). Vaccination was feared on the European continent as well as in England. This French caricature satirized that fear. It shows a woman with smallpox turning into a mermaid, a physician riding a cow, and an apothecary with a giant syringe pursuing frightened children. (Courtesy of the Wellcome Library, London, United Kingdom.)

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