CHAPTER 2 Smallpox

Smallpox is an ancient disease, perhaps even older than plague, that seems to have first arisen among the earliest human civilizations with settled populations large enough to sustain its epidemics, such as in Mesopotamia, Egypt, or the Indus River valley.

Smallpox is caused by a virus, a microscopic infectious disease agent that, un­like a bacterium, is an incomplete organism that needs to invade a host cell in order to reproduce and spread within the body. It consists of nucleic acid, either DNA or, more commonly, RNA, surrounded by a protein coat that allows the virus to attach itself to a host cell and then penetrate it in order to use the host cell's biological mechanisms to replicate itself. Some viruses, instead of simply duplicating the viral genome, use their RNA template to manufacture DNA, a process known as reverse transcription; one class of these viruses, known as ret­roviruses, which includes the human immunodeficiency virus (HIV) that causes AIDS (acquired immune deficiency syndrome), are particularly insidious as they incorporate their manufactured DNA into that of the host cell, thus making this “Frankenstein’s monster” practically indistinguishable from other, healthy cells.

Smallpox probably originated as a virus prevalent in an animal reservoir that then made the jump to humans following the domestication of animals some eleven or twelve thousand years ago. It is a member of the orthopoxvirus family, which includes viruses that also affect monkeys, rodents, cats, camels, elephants, and water buffalo and cattle; the last is probably the most likely contender as the vector that passed the smallpox virus from animals to humans.⁴ Even today, cowpox and buffalopox viruses can cause mild infections in human victims, typically by milking infected udders. There are two main types of the smallpox virus, Variola major and Variola minor, with the former being the more com­monly occurring in human history and also the more deadly, killing on average about a third of its victims. Infection with Variola minor was almost a godsend, as it killed just 1 percent or less of those who contracted it, yet it conferred life­long immunity to the disease, even in its more severe form. The virus itself was not physically seen and identified with an electron microscope until the 1940s, even though awareness of viruses as organisms distinct from bacteria, which was achieved through special, fine filters that could separate the two, was achieved by the end of the nineteenth century. The Latin term, variola, which in the Middle Ages came to mean “pox” and was probably derived from the Latin word for “spotted” (varius) or “pimple” (varus), was first used in connection with the disease during the sixth century C.E.

Smallpox’s symptoms were intimately bound up with how the disease was spread. After an incubation period of nine to twelve days, the victim typically experienced a violent fever accompanied by chills, nausea, aches and pains, and sometimes convulsions and delirium. Then a rash of small reddish spots ap­peared on the mucous membranes of the mouth, tongue, upper palate, and throat, which quickly enlarged and ruptured, releasing millions of viruses into the saliva, making the disease highly contagious at this stage from person to person by means of droplet infection. Next, the virus invaded the outer skin cells, forming raised pimples and then broader pustules filled with fluid (not pus) that became opaque and then slowly leaked out until the lesions dried up, scabbed over, and flaked off, which happened two to three weeks later. Scarring and sometimes blindness occurred, leaving the characteristic pockmarks that forever signaled to the world a victim of smallpox. Since the pustules formed heaviest on the face and the extremities, smallpox was a very visible disease, practically impossible to hide, so that even though the victim was infectious for as long as he or she exhibited its symptoms, it was also abundantly clear who had the disease and thus who should have been avoided.

Nevertheless, the scabs and liquid “matter” of smallpox victims present in their clothing or bedding (what the sixteenth-century physician Girolamo Fracastoro called the “fomites” or seeds of disease) could still have infected others even when no direct contact was made with the victims themselves; usually, however, small­pox contagion occurred through close, direct contact with victims, such as often happened among members of the same household, and when victims were in the most infectious stage of the disease during the first week of the rash appearing on their bodies.

The history of smallpox is mainly characterized by the differential way in which it strikes its victims, both within a given society or culture and between sometimes competing civilizations. Smallpox in this respect is therefore quite different from plague, which confers no compensating immunity upon those who are made to suffer its ravages and which during the time of the Black Death in late medieval Europe had a notorious reputation, even if this was not borne out in fact, of equitably harvesting its victims, as evidenced by the popular Dance of Death artistic motif that was frequently associated with plague, in which various members of the social hierarchy, in descending order from pope and emperor on down to hermit and poor man, must all dance a reel with death.⁵ Smallpox then had a very different dynamic from plague, in which its impact was felt not so much through any massive mortality on the scale of the Black Death but instead through the simple reality that not everyone was killed off or even affected by the disease.

The major epidemics of smallpox around the world and throughout history amply reveal its distinguishing, differential characteristic. Perhaps the first out­break to receive the attention of ancient historians of disease was the Plague of Athens of 430—426 B.C.E., as chronicled by Thucydides. We have already ex­plored in the introduction the issues of identifying the Plague of Athens with smallpox and its long-term impacts upon Athens' conduct of the Peloponnesian War. Smallpox accords well not only with Thucydides' description of symptoms but also with his account of its rapid spread; although the disease seems to have died down after 426, giving the Athenian population a chance to recover its former numbers, its early timing may well have set the stage for the city's conduct during the rest of the war by supposedly undermining its celebrated veneer as a civilized, moral standard-bearer for Greece—or, to borrow Thucydides' phrase as put into the mouth of Pericles, as the “school of Hellas”—that was used to justify the war in the first place.

But for our purposes here, the main thing to be noted about the Plague of Athens is how it coincided with war and at the same time with a lopsided mortal­ity and morbidity that affected only one side in the conflict, a fact that was duly noted by Thucydides.

The next major outbreak of smallpox to be recorded in history is believed to be the Plague of the Antonines, which struck the Roman Empire beginning in 165 C.E., during the reign of the last of the Five Good Emperors, Marcus Aure­lius Antoninus (161—180), who seems to have died of the disease, and extending perhaps into that of his son, Lucius Aurelius Commodus Antoninus (180—192). While no hard mortality statistics are available for this epidemic, best estimates are that it carried off 10 percent of the empire's population, which would be enough to make an impact, certainly, but not so much that a relatively swift re­covery could not be made. Nonetheless, it has been argued that, once again, smallpox was ill timed to coincide with war, when the empire began facing chal­lenges from the Parthian Empire in the east and from the Germans to the north; the loss of manpower to disease at such a critical time may have made a differ­ence in Rome's future ability to fight off the “Barbarian” threat and compelled it to recruit soldiers from among the Germans themselves in order to make up the numbers, a policy that would have grave implications later by the end of the empire in the fifth century.⁷

The Middle Ages saw an important breakthrough in medical diagnosis and treatment of smallpox when the Persian physician, Muhammad ibn Zakariya al-Razi (865—925), known simply as Rhazes in the West, composed his Treatise on the Small-pox and Measles based on his experience treating patients as head of the hospital at Baghdad, the capital of the Abbasid caliphs. Rhazes provided the first definitive symptomatology of smallpox, distinguishing it from measles pri­marily by the presence of severe backache, but he also noticed that smallpox was characterized by a “continuous fever,” a “stinging pain in the whole body,” a “violent redness of the cheeks and eyes,” as well as a “pain in the throat and breast,” all of which were also noted by Thucydides during the Plague of Athens. Rhazes also supplied the important evidence that smallpox was primarily a child­hood disease in his time, which indicates that it had by now become endemic to the Eurasian continent as a regularly occurring disease.⁸

By far the most controversial, notorious, and studied outbreak of smallpox in human history seems to be that which occurred in the American hemi­sphere—Mexico, the Caribbean, and Central, South, and North America— beginning in the early sixteenth century and raging through to the next cen­tury and beyond. This has been called nothing less than an American “Holocaust” or “Apocalypse” of mortality among the native populations of these regions, but it must be remembered that it took at least a century for such demographic losses to be registered in what records we have; what is more, a panoply of diseases besides smallpox helped bring about the catastro­phe, including other directly contagious ills like measles, influenza, pneumonic plague, and mumps, as well as those spread by other means such as an insect vector or contaminated water supplies, which would include typhus, bubonic plague, yellow fever, malaria, and cholera. Smallpox, however, was among the earliest and apparently most deadly diseases to strike the Americas, making landfall first on the island of Hispaniola (modern-day Dominican Republic and Haiti) in 1518 and then the mainland of Mexico in 1520 in the wake of the expedition of Hernan Cortes that culminated with the conquest of the Aztec Empire. Around the same time, during the 1520s, smallpox also arrived in Guatemala, Panama, and Ecuador in Central and South America. Through­out the rest of the century, smallpox reappeared somewhere in the western hemisphere on a regular basis almost every other decade; it finally appeared in Brazil in 1562, and by the end of the century it was the turn of the natives in North America to also feel its wrath. Smallpox seems to have arrived first in the southwestern United States and northern Mexico during the 1580s and 1590s, then the northeastern region in the second or fourth decade of the seventeenth century, followed by Florida and the southeast in 1655, and finally the Pacific Northwest and Great Plains during the 1780s. In the latter two regions, smallpox continued its ravages even into the first half of the nine­teenth century, before federal vaccination efforts took effect. Even though Old World diseases came later to Brazil and North America compared to the rest of the hemisphere, and native populations there were more dispersed than in the population centers of the Aztec and Inca empires, declines are estimated to be just as great as anywhere else, especially since Brazil and North America be­came just as much, if not more, active in the slave trade from Africa, which was another source of disease introduction to the New World.⁹

Much debate still exists as to the exact numbers of victims who succumbed at this time: mainly the issue centers around pre-Columbian estimates of popula­tion, which must rely on inexact measures such as anecdotal testimonial evi­dence, archaeological artifacts, and educated guesses as to the “carrying capacity” of the land. Mexico, for example, may have had a total native population in 1519 ranging from three to fifty-eight million, which would put its decline by 1605 at anywhere from 67 to 98 percent; the Andes region in South America may have numbered from two to thirty-seven million in 1532, making its decline by 1620 somewhere between 70 and 98 percent.¹⁰ But even when opting for the lowest estimates of population loss, the Native American die-off was enormous, prompting one historian, David Noble Cook, to dub it the “greatest human catastrophe in history.”¹¹

For an older generation of historians, led initially by John Duffy, Alfred Crosby, and William McNeill, disease was assigned an almost monocausal role in the American Holocaust, even when other factors besides the introduction of germs, such as the importation from Europe of new plants and animals to the Americas, were invoked to explain how disease was able to wreak its havoc.¹² Disease was able to reach such tragic proportions in the Americas supposedly because it took root in the “virgin soil” of a population that had no prior expo­sure to Europe's epidemics, even though Native Americans did have their own, pre-Columbian illnesses, including dysentery and other gastrointestinal diseases, tuberculosis, fungal and streptococcal infections, bacterial pneumonia, and pos­sibly malaria, yellow fever, typhus, and influenza. They also had some form of venereal disease, such as syphilis, that may have been their “gift” back the other way to the Europeans. Yet, the successive waves of ever-changing epidemic dis­ease crashing in on American shores with each new generation of settlers or slaves arriving from Europe and Africa never gave natives a chance to recover their numbers from any single outbreak; even in the case of those who survived a bout with smallpox or measles and thus developed immunity to it, there was always the specter of some new illness on the horizon to claim its share of victims. For example, after Mexico's disastrous encounter with smallpox during the 1520s, measles struck Mexico and Central America during the 1530s, then it was the turn of typhus and possibly pneumonic plague in the 1540s, followed by a lethal combination of smallpox, influenza, and measles in Guatemala and the Andes during the 1550s and 1560s, with typhus added to the mix during the 1570s, 1580s, and early 1590s.¹³

For some scholars, no other explanation aside from disease need be considered in order to account for the precipitous decline in numbers and, by implication, in cultural vitality, of Native American populations during the century or more following Columbus's first contact in 1492. Thomas Whitmore, for instance, declares that the “presumption of disease mortality as the overwhelming cause of Amerindian population decline throughout the New World seems virtually ir­refutable,” since “the principle of Occam's razor [that the simplest explanation is best] suggests that it is not necessary to assume that there were other important causes of death.”¹⁴ Others, drawing on the older positions of disease historians like Hans Zinnser and Henry Sigerist, also place some emphasis on the mercurial nature of disease to mow down the “great actors” of history, such as the Aztec leader Cuitlahuac and the Inca emperor Huayna Capac, both of whom suc­cumbed to smallpox, in sealing the fate of American civilizations.¹⁵ But did disease really act alone to deal out all this damage? More recent scholars of the New World Holocaust seem not so satisfied with this answer.

Instead, the latest consensus has coalesced around the idea that disease must interact with other cultural factors, in this case primarily colonial or imperialis­tic oppression, in order to satisfactorily explain the collapse of Native American societies. Perhaps the most persuasive argument to be made for this position is a comparative one, in which the smallpox epidemic in the Americas is analyzed alongside the outbreak of plague in Europe during the late Middle Ages, which we just explored in the previous chapter. Why did Europe recover, both cultur­ally and in demographic terms, from its bout with deadly epidemic disease at the dawn of the Early Modern period whereas at this very same time American civilizations were about to embark on a completely different trajectory with the arrival of their own plagues? Keep in mind that the Black Death, no less than smallpox in the Americas, behaved as if it were rampaging on virgin soil in Europe, given the extremely high mortalities achieved in just a few years. Also remember that plague kept coming back to decimate European populations in successive waves in succeeding decades, just as smallpox did in the New World, and that it likewise did so in conjunction with other illnesses, albeit ones per­haps not as deadly as each new disease was in the Americas.¹⁶ One study based on the obituary lists for Christ Church Priory in Kent throughout the fifteenth century reveals that plague, a killer in a third of all disease outbreaks among the monks, was accompanied by tuberculosis, the “sweat” (a mysterious deadly disease characterized by chills, fever, and profuse sweating that first broke out in England in 1485), dropsy or edema, and strangury (a painful inability to urinate).¹⁷ A doctor writing from Avignon in 1382, Raymond Chalin de Vi­nario, also pointed to the “great variety of epidemic diseases” that were appear­ing in his time, including ulcerous scabies (a skin itch or rash), intestinal worms, and “semi-tertian fevers” (malaria).¹⁸

The obvious answer to this comparative conundrum seems to be that Europe hadn't had to face an invasion by another civilization bent on its conquest at the same time that it was being conquered by disease, a civilization that was not only ruthless and in some ways technologically superior but also, most significantly, seemingly immune to the very diseases before which the natives were so helpless. Imagine if, during the Black Death, Europe also faced a massive onslaught from the Mongol Empire, in which the invading Mongol armies were indifferent to the plague, rather than being just as susceptible to it as the Europeans, and in­deed seemed to use the disease as their ally. Would Europe as we know it have survived? This scenario is not so very far-fetched as it might seem; just a century earlier the armies of the Great Khan had reached the gates of Vienna before the death of their leader called them back east, and we have already seen how in 1346 the Mongols at Caffa communicated the plague to some Genoese mer­chants through a form a biological warfare, even as their own ranks were falling to the Black Death.

It has recently been argued that the Mesoamerican experience with disease during the sixteenth and seventeenth centuries in many ways mirrored that of the Europeans and other cultures during their own epidemic crises, such as the Black Death. This similarity extends to the severity of each disease outbreak, which in both Europe and the Americas supposedly averaged between 25 and 50 percent; the circumstances surrounding epidemics in both regions were likewise comparable, being caused and spread primarily by trade contacts and networks and accompanied by exacerbating factors such as warfare. Human responses to disease among Native Americans could also strike similar chords in other cul­tures, such as their attribution of outbreaks to a combination of divine or super­natural causes and natural ones, and their explanation of the occurrence of dis­ease in humans as owing to an imbalance that needed to be corrected if prevention or cure was to be effected. For example, Andean healers believed in the three fluids of life of air, blood, and fat that correspond to the Indian Ayurvedic dosas or the Greek humoral system, while the Aztecs subscribed to a cosmic dualism that has parallels with the yin-yang concept in China.¹⁹ As in Europe and the Middle East, the Aztecs also usually attributed disease to a higher power such as their gods, whom they believed they had offended in some fash­ion, and they treated illnesses through a familiar combination of prayer, blood­letting, diet (expressed in opposites of hot and cold), and herbal remedies, in which they were known to be particularly expert.²⁰

The disease Holocaust in the New World should therefore not be taken as the exception to the human experience with epidemics that it has traditionally been thought but rather needs to be fully integrated into the overall history of disease. At the same time, however, even the proponents of this view will admit there are some aspects of the American experience with disease that are uniquely tragic and catastrophic. One difference is the confluence of “virgin soil” diseases that struck the Americas almost simultaneously compared to the rest of the world, especially since Europe, Africa, China, and India were all interconnected epidemically by ancient trade patterns that made them part of one “disease pool,” with the result that European colonialism within this pool did not enjoy the same demographic advantages as it did in the New World. Of far greater impact, however, was the simultaneous occurrence of colonial oppression, popularly known as the “Black Legend,” that was chronicled by propagandists even among the Spanish them­selves, such as the Dominican friar Bartolome de las Casas, which augmented and sometimes exacerbated the massive population losses to disease. Here, untold thousands succumbed to a combination of outright military conquest, slavery, and forced labor and migration. Although these losses have long been known to scholars, and indeed have lately been discounted somewhat as the product of propaganda exaggeration, until now the implications of their interconnectedness with the concurrent die-offs due to disease have not been fully realized.²¹

It is true that in Europe, too, disease often coincided with warfare, sometimes with deliberate timing, as when Florence launched attacks on its rivals on the Italian peninsula to coincide with outbreaks of plague during the late fourteenth and early fifteenth centuries.²² But there is probably nothing to compare with the concerted assault from European colonial powers upon the disease-ridden New World, an assault that, unlike the wars in Europe, came from an entirely alien culture that, as already mentioned, was largely immune to the epidemics decimating its rival civilizations. In the territories administered by Spain, Portu­gal, and France, it can confidently be asserted that the native die-off from disease was unintentional, since these countries relied on indigenous labor and contacts in order to exploit their colonies for their benefit. In the English colonies of North America, however, the settlers' hunger for land was entirely inimical to the natives' presence, and so the latter's epidemiological misfortunes were actually celebrated or even deliberately planned, as in the famous incident of Jeffrey Am­herst, British commander at Fort Pitt in present-day Pennsylvania, ordering the distribution of smallpox-infected blankets among the Ottawa tribe during the Pontiac rebellion of 1763 as a form of biological warfare. But even among those whose treatment of the natives could be said to be the least detrimental to their survival, such as the Catholic missionaries in New Spain and New France, their policies of resettlement or reducciones of Native American populations, whereby whole tribes were herded together into missions for the purposes of conversion, unwittingly helped spread crowd diseases like smallpox much faster and more effectively than if their charges were simply left alone.

I also believe that, aside from the numbers directly killed by its impact, Eu­ropean colonialism interacted in a synergistic way with disease to greatly aug­ment population losses during epidemics, in that colonial policies helped to drastically lower native cultural abilities to resist and recover from epidemio­logical setbacks. Whereas Europe was able to weather and eventually overcome the long demographic stagnation imposed by the Black Death from 1348 until at least 1450, Native Americans by contrast were at a severe cultural disadvan­tage for doing so, quite aside from the sheer number, severity, and timing of the epidemics themselves. For example, it has been asserted that both European and Native American societies responded to major disease outbreaks with terror, fear, and despair; I have argued elsewhere, however, that such a characterization has been grossly exaggerated when describing the European response to the Black Death in the late Middle Ages. An assortment of humanists, doctors, art­ists, mystics, and even clergymen began formulating alternatives to the obses­sively morbid “guilt culture” that supposedly imbued late medieval Europe in the aftermath of the Black Death.²³

On the other hand, such fatalistic attitudes are more believable in the New World in the context of the intersection between the Black Legend and disease. Contemporary reports, mostly from European observers, do testify to natives who succumbed to suicide, self-inflicted abortions, reluctance to reproduce, and other symptoms of a demoralized and defeated mentality. The mood seems cap­tured by the Yucatan Book of Chilam Balam of Chumayel, which bemoans, “Great was the stench of the dead. After our fathers and grandfathers succumbed, half of the people fled to the fields. The dogs and vultures devoured the bodies. The mortality was terrible.... So it was that we became orphans, oh my sons! So we became when we were young. All of us were thus. We were born to die!”²⁴ Small­pox was very conducive to this depressed outlook among survivors because of the disfigurement it produced, to which some Native American cultures that appar­ently prized the beauty of their complexions were particularly sensitive. Studies of the impact of “virgin soil” epidemics in the Hawaiian islands during the eigh­teenth and nineteenth centuries, where smallpox was perhaps the most feared of all diseases that also included measles, mumps, whooping cough, chickenpox, influenza, and tuberculosis, nonetheless conclude that declining birth and fertil­ity rates and high male-to-female ratios were primarily responsible for the drastic population declines in the region. Sterility caused by venereal diseases such as syphilis and gonorrhea are largely held to blame, but a collective cultural suicidal impulse brought on by racial oppression from white haole colonists and mission­aries—expressed in the form of abortions and suicides induced either deliber­ately or through simple neglect or “anomie”—are also believed to have played a role, particularly in skewing the relative proportions of the sexes. Venereal dis­eases may likewise have been facilitated by cultural attitudes such as the reputed open sexual mores of the Hawaiians.²⁵

Even when Native American responses to disease are similar to those in other cultures, the fact that these responses were not allowed to express themselves in isolation but were impinged upon by the responses of a completely different culture changes the dynamics of the outcome. A good example of this is the typical explanation of disease as the product of the displeasure of the gods, an outlook that natives in the New World shared with the new arrivals from the Old World. As if the wrath of one's own gods was not bad enough, Native Americans were also told that the rival Christian God likewise caused disease, so that they were then caught in an epidemiological catch-22, being subject to some kind of epidemic punishment no matter whom they worshipped. I think it also possible that the differential mortality and morbidity with which a disease like smallpox afflicted Native Americans as compared with Europeans (for whom, at least dur­ing the Middle Ages, smallpox seems to have behaved like a relatively mild child­hood disease) encouraged New World societies to view their gods as defeated by the one God of the Christians,²⁶ especially since they already viewed their own gods as sometimes battling each other, such as the Aztec legend of the defeat and banishment of Quetzalcoatl by Tezcatlipoca.

Another parallel set of responses that actually turns out to be dissimilar is the tendency to flee any occurrence of a disease, even when it occurs among one's own family, which we have seen was widely reported in Europe during the Black Death and was likewise observed among Native Americans during smallpox epi­demics. (Only in the Muslim Middle East does there seem to have been a cul­tural antipathy against flight.) Yet, here again, the experience was not the same. Not only did flight threaten to disrupt the traditional communal bonds holding together a society, as Giovanni Boccaccio complained it did in Florence during the Black Death, but also to this was added in the New World the humiliating spectacle of some Europeans, such as the Jesuit missionaries, being more chari­table toward the natives than the natives themselves as they stayed behind to nurse the sick. It is quite likely that European medicine at this stage was no more effective in treating smallpox than native healing methods. Although some have blamed the traditional indigenous practice of resorting to sweat lodges alternat­ing with cold baths or immersions in lakes for fatally exacerbating the illness, European observers tended to view any kind of bathing with suspicion on both moral and humoral grounds, while some European doctors, such as a Master Bernard of Frankfurt and Theobaldus Loneti of Besanqon, advocated their own sweating regimens as a cure for plague.²⁷ But because European healers in the New World such as the Jesuits had the great advantage of being seemingly im­mune to a disease like smallpox, they were able to fill a void left by native sha­mans and hechicheros who had failed to cure illnesses with their own brand of magic and so were able to persuade many natives to abandon their own belief systems, as one study of the impact of disease upon native culture in northwest­ern New Spain has found. In addition, agents of colonialism such as the Jesuits already had an ideological framework in place with which they could readily explain and rationalize epidemics of smallpox.²⁸

Even as the symbiotic relationship between disease and cultural imperialism was playing itself out in the New World, smallpox was once again gaining in virulence in the Old World, perhaps as a result of the reimportation of a new Variola major strain from the Americas back to Europe. From the second half of the sixteenth century, smallpox epidemics started to recur more frequently, until by the close of the seventeenth century smallpox had become the predominant disease in Europe, apparently bypassing plague, leprosy, and syphilis as the leading killer throughout the Continent. Much of this was aided by the fact that urban populations were rising and warfare was incessant, both of which facilitated the spread and prevalence of a disease like smallpox.²⁹ During the eighteenth century, however, Europeans finally acquired the tools to combat the rising tide of small­pox: the century was bracketed by the introduction of the technique of inocula­tion at its beginning and the discovery of vaccination by its end.

Inoculation, also known as variolation, is the deliberate introduction of a weak­ened form of smallpox into the patient in order to induce a mild case of the disease and so create immunity to it and was widely practiced in Istanbul toward the end of the seventeenth century, after the Turks learned of it from the Chinese or the Persians. By the dawn of the next century, several European observers in Istanbul began communicating their newfound awareness of the practice, the most famous being Lady Mary Wortley Montague, wife of the British ambassador to Turkey, who eventually introduced it to England in 1721. Around this same time, inocula­tion also found its way to the American colonies, when the Reverend Cotton Mather of Boston learned of the practice from his West African slave, Onesimus, and from other slaves in Boston who reported that it was long and widely practiced in western Africa. Later, inoculation was to play a role in the American Revolution, when General George Washington had his soldiers inoculated in order to forestall germ warfare from the British, who were generally more immune to the disease.³⁰

Then, on May 14, 1796, Dr. Edward Jenner performed his famous vaccination of a patient, an eight-year-old boy named James Phipps, with cowpox lymph taken from a sore on the hand of a milkmaid, Sara Nelmes. This was by no means the first recorded vaccination, but it was the most influential in that Jenner demon­strated that it could induce immunity to smallpox without the side effects of in­oculation. Indeed, it is even claimed that vaccination can be traced all the way back to ancient Ayurvedic medicine in India. During the nineteenth century, vaccina­tion became compulsory in many European countries, even though there was opposition mainly on the grounds of safety in terms of other diseases that might be communicated with the vaccine, and on the grounds of efficacy in that the im­mune response generated by vaccination was not lifelong, as in the case of inocula­tion. Ironically, the drastic decline of smallpox in Europe only facilitated antivac­cinators’ objections due to the waning urgency of vaccination itself.³¹ These objections were largely overcome through the development of better vaccines and revaccination programs. It should also be pointed out that, despite the advent of vaccination, smallpox continued to devastate “virgin soil” populations throughout the nineteenth century in the Americas, the Pacific Islands, and among the Ab­original peoples in Australia, while a more virulent strain of the disease wreaked havoc in West Africa even though it had been endemic there for centuries.

Resistance to nineteenth-century vaccination programs was encountered by European governments not only at home but also in its colonies abroad. A prime example of this is the British experience in India, where expectations were high that vaccination would be gratefully and joyfully received by natives as a benevolent marvel of Western medicine and so help cement imperial political rule in the country. But as with its later measures against the Third Pandemic of plague, the British disastrously underestimated the extent of native resistance to vaccination. These included some Hindu religious objections that were unique to India, such as that arm-to-arm transmission of the cowpox lymph might violate caste taboos and reverence for the sacred inviolability of the cow, but they also shared some of the same concerns that motivated protests in Europe, such as the unreliability of the vaccine. India also had a strong and ancient local tradition of variolation and of religious rituals centered on the smallpox goddess, Sitala. Even though British medical authorities regarded native inoculators, known as tikadars, to be their rivals in terms of implementing their own vaccination programs, eventually they were forced by fears of widespread political unrest to adopt a more low-key, collaborative policy whereby they recruited tikadars as vaccinators. It was not until the end of the century that vaccination because more available and widespread in India.³²

Another “vaccination revolt” in a former European colony famously occurred in Rio de Janeiro in Brazil in November 1904. Here the European-influenced government of Rodrigues Alves, advised by a young bacteriologist named Os­waldo Cruz, regarded vaccination as a humanitarian blessing of the new, modern, scientific approach to disease, just as the British did in India. However, the city’s Afro-Brazilian population preferred its native practice of variolation inherited from Africa, while socialists and other political opponents of Brazil’s oligarchic regime protested the “sanitary despotism” of such public health measures being imposed by the government.³³ Antivaccination sentiments have not gone away even in this day and age; during the writing of this book, I saw a bumper sticker that said, “Say No to Forced Vaccinations.” Today, the issue primarily concerns vaccines developed for influenza, of which more will be said in chapter 5.

The final chapter of the history of smallpox is the successful eradication of the disease during the twentieth century. By the time the Smallpox Eradication Pro­gram was announced by the World Health Organization (WHO) in 1966, with a goal of global eradication in ten years' time, smallpox was still endemic in South America, sub-Saharan Africa, and the Indian subcontinent and archipela­gos of Southeast Asia. Almost miraculously, the program completed its eradica­tion campaign on schedule, with the last case of Variola major reported in Ban­gladesh in 1975 and of Variola minor in Somalia in 1977. Complete, certifiable eradication was finally announced by WHO in 1979, which was achieved largely by a “surveillance-containment” strategy that focused only on vaccinating those who were in contact with known cases of smallpox.³⁴

Today, the only controversy that still exists with respect to smallpox is whether or not to destroy the last known remaining stocks of the virus at the U.S. Centers for Disease Control in Atlanta and at the Russian State Research Center of Virol­ogy and Biotechnology in Novosibirsk. Originally, WHO had scheduled the fi­nal execution of the virus to take place on June 30, 1999, but a stay of execution was granted indefinitely at the behest of the administration of former U.S. president George W. Bush in 2001 in the immediate aftermath of the September 11 terrorist attacks. On the one hand, execution makes sense if only to avoid tragic mishaps with the virus, such as happened in Birmingham, England, in 1978, when the virus escaped from a research laboratory there, killing one per­son and driving another, the man in charge of the laboratory, to suicide. There is also the fear that some of the remaining supplies could somehow end up in the wrong hands and become an agent of bioterrorism, in which the virus would act almost like a virgin soil epidemic, since it has been three decades now since any­one got the disease or has been vaccinated. The dangers of even waste material from the laboratory was illustrated in 2000, when eight children at Vladivostok in Russia were diagnosed with a mild case of smallpox after playing with glass ampoules containing expired smallpox vaccines at the city's garbage dump. On the other hand, others, including Donald Hopkins, perhaps the greatest author­ity on smallpox, who has authored a history of the disease and participated in the Smallpox Eradication Program, argue for keeping stocks of the virus alive for research purposes and as insurance in case somehow another epidemic should break out that would require developing more or better vaccines. In 2004, for example, WHO approved genetic manipulation of the smallpox virus in order to develop drugs for treating the disease, once again in response to renewed fears of possible bioterrorism attack.³⁵ (To date, no cure is available for smallpox, only a vaccine.) All this shows that, once again, smallpox plays a differential role in his­tory, even at the very putative end of its existence, when its fate is in the hands of only two countries that still have stocks of the virus. We can only hope that, regardless of the outcome of this debate, smallpox as a disease will remain con­signed to the pages of history.