A second reason historians believe that epidemics tore through Native American communities before Europeans arrived is that epidemics also did it after Europeans arrived. In her book Pox Americana (2001), the Duke University historian Elizabeth Fenn meticulously pieced together evidence that the Western Hemisphere was visited by two smallpox pandemics shortly before and during the Revolutionary War. The smaller of the two apparently began outside Boston in early 1774 and lurked in the area for the next several years like a sniper, picking off victims at the rate of ten to thirty a day. In Boston the Declaration of Independence was overshadowed by the previous day’s proclamation of a citywide campaign of inoculation (an early, risky form of vaccination in which people deliberately infected themselves with a mild dose of smallpox to produce immunity).

Even as it besieged Boston, the virus also spread down the eastern seaboard, laying waste as far as Georgia. It wreaked havoc on the Ani Yun Wiya (the group often called the Cherokee, which is a mildly insulting name coined by their enemies, the Creek confederation) and the Haudenosaunee (the indigenous name for the six nations that made up what Europeans called the Iroquois League). Both were important allies of the British, and after the epidemic neither was able to fight the colonists successfully. Smallpox also ruined the British plan to raise an army of slaves and indentured servants by promising them freedom after the war—the disease killed off most of the “Ethiopian regiment” even as it assembled.

An equal-opportunity killer, smallpox ravaged the rebels, too. The virus had been endemic in Europe for centuries, which meant that most Europeans were exposed to it before adulthood. But it was only an occasional, terrible visitor in the Americas, which meant that most adult colonists had not acquired childhood immunity. On an individual level, they were almost as vulnerable as Indians. On a group level, though, they were less genetically homogeneous, which conferred some relative advantage; the virus would sweep through them, but not kill quite so many. Still, so many soldiers in the Continental army fell during the epidemic that revolutionary leaders feared that the disease would bring an end to their revolt. “The small Pox! The small Pox!” John Adams wrote to his wife, Abigail. “What shall We do with it?” His worries were on target: the virus, not the British, stopped the Continental army’s drive into Quebec in 1776. In retrospect, Fenn told me, “One of George Washington’s most brilliant moves was to inoculate the army against smallpox during the Valley Forge winter of ’78.” Without inoculation, she said, the smallpox epidemic could easily have handed the colonies back to the British.

Even as the first outbreak faded, Fenn wrote, a second, apparently unrelated epidemic burned through Mexico City. The first cases occurred in August 1779. By year’s end perhaps eighteen thousand had died in the city area and the disease was racing through the countryside in every direction. Communications in those days were too poor to permit us to document a transmission chain, but records show smallpox flaring in separate explosions to the south like a chain of firecrackers: Guatemala (1780–81), Colombia (1781–83), Ecuador (1783). Was the virus retracing a journey to Tawantinsuyu it had taken before? “It seems likely,” decided Calloway, the Dartmouth historian. Fenn tried to trace the virus as it went north. Like Dobyns, she examined parish burial records. In 1780 a telltale surge of mortality traveled north along the heavily traveled road to Santa Fe. From there, smallpox apparently exploded into most of western North America.

First to suffer, or so the sketchy evidence suggests, were the Hopi. Already reeling from a drought, they were blasted by smallpox—as many as nine out of ten may have died. When the Spanish governor tried to recruit the Hopi to live in missions, their leaders told him not to bother: the epidemic soon would expunge them from the earth. As if drought and contagion were not enough, the Hopi were constantly under attack by the Nermernuh (or Nemene), a fluid collection of hunting bands known today as the Comanche (the name, awarded by an enemy group, means “people who fight us all the time”). Originally based north of Santa Fe, the Nermernuh were on their way to dominating the southern plains; they had driven away their Apache and Hopi rivals with trip-hammer ambushes and deadly incursions and were bent on doing the same to any European colonists who ventured in. In 1781 the raiding abruptly stopped. Silence for eighteen months. Was the ceasefire due to Mexico City smallpox that had been transmitted by the Hopi? Four years afterward, a traveler noted in his diary that the Nermernuh lived in fear of disease because they had been recently struck by smallpox—tenuous but suggestive evidence.

What is certain is that both Hopi and Nermernuh were part of a network of exchange that had hummed with vitality since ancient times and had recently grown more intense with the arrival of horses, which sped up communication. Smallpox raced along the network through the Great Plains and the Rocky Mountains, ricocheting among the Mandans, Hidatsas, Ojibwes, Crows, Blackfoot, and Shoshone, a helter-skelter progress in which a virus leapfrogged from central Mexico to the shore of Hudson Bay in less than two years. Indians in the northern Great Plains kept “winter counts,” oral chronologies of the most important events in each year. Often the counts were accompanied by a spiraling sequence of drawings on a hide, with each year summarized by a drawing as an aide-mémoire. In several Lakota (Sioux) counts 1780–81 was bleakly summed as the year of Smallpox Used Them Up; and the Lakota were not the only ones affected.

In 1781 a company of Blackfoot stumbled across a Shoshone camp at dawn near the Red Deer River in Alberta. The Blackfoot were a tightly organized confederation of groups that inhabited the plains between the Missouri and Saskatchewan Rivers. Equipped with guns and horses from French traders, they had pushed their southern neighbors, the Shoshone—left at a disadvantage because they had no access to the French and their goods, and the Spanish, whom they did have access to, tried to block Indian access to weapons—from the plains into the mountains of what are now Wyoming and Colorado. When the Shoshone finally obtained guns—they traded with their linguistic cousins, the Nermernuh, who took the weapons as booty from defeated Spaniards—open warfare broke out. In this bellicose context, the Blackfoot party knew exactly what to do when it happened upon a slumbering Shoshone encampment. With “sharp flat daggers and knives,” one of the raiders later remembered, they silently sliced open the Shoshone tents “and entered for the fight; but our war whoops instantly stopt, our eyes were appalled with terror; there was no one to fight with but the dead and the dying, each a mass of corruption.” The Blackfoot did not touch the bodies, but were infected anyway. When the company returned home, the raider lamented, smallpox “spread from one tent to another as if the Bad Spirit carried it.”

According to Fenn, “the great preponderance of the evidence” indicates that the Shoshone also transmitted smallpox down the Columbia River into the Pacific Northwest. Calloway suggests the Crow as a plausible alternative. Whoever passed on the virus, its effects were still visible a decade later in 1792, when the British navigator George Vancouver led the first European expedition to survey Puget Sound. Like Cook’s crew in Kamchatka, he found a charnel house: deserted villages, abandoned fishing boats, human remains “promiscuously scattered about the beach, in great numbers.” Everything they saw suggested “that at no very remote period this country had been far more populous than at present.” The few suffering survivors, noted Second Lieutenant Peter Puget, were “most terribly pitted…indeed many have lost their Eyes.”

Europeans were well versed in the brutal logic of quarantine. When plague appeared, they boarded up houses and fled to the countryside. By contrast, the historian Neal Salisbury observed, family and friends in Indian New England gathered at the sufferer’s bedside to wait out the illness, a practice that “could only have served to spread the disease more rapidly.” Even the idea of contagion itself was novel. “We had no belief that one Man could give [a disease] to another,” the Blackfoot raider remembered, “any more than a wounded Man could give his wound to another.” Because they knew of no protective measures, the toll was even higher than it would have been.

Living in the era of antibiotics, we find it difficult to imagine the simultaneous deaths of siblings, parents, relatives, and friends. As if by a flash of grim light, Indian villages became societies of widows, widowers, and orphans; parents lost their children, and children were suddenly alone. Rare is the human spirit that remains buoyant in a holocaust. “My people have been so unhappy for so long they wish to disincrease, rather than to multiply,” a Paiute woman wrote in 1883. A Lakota winter count memorialized the year 1784 with a stark image: a pox-scarred man, alone in a tipi, shooting himself.

Disease not only shattered the family bonds that were the underlying foundation of Indian societies, it wiped out the political superstructure at the top. King Liholiho Kamehameha II and Queen Kamamalu of Hawai‘i visited Great Britain on a diplomatic mission in 1824. While staying in a posh London hotel and attending the theater in the English king’s own box, the royal couple and most of the rest of their party came down with measles. It killed the queen on July 8. The grieving king died six days later, at the age of twenty-seven. The death of the royal couple ushered in a time of social chaos. It was as catastrophic for Hawai‘i as the death of Wayna Qhapaq for Tawantinsuyu.

A particularly poignant loss occurred in the summer of 1701, when the leaders of forty native nations convened in Montreal to negotiate an end to decades of war among themselves and the French. Death stalked the congress in the form of influenza. By then the Indians of the Northeast knew such diseases all too well: sickness had carried off so many members of the Haudenosaunee that the alliance was forced to replenish itself by adopting abductees and prisoners of war. At the time of the conference at least a quarter of the Haudenosaunee were former captives. At great personal risk, many Indian leaders attended the conference even after they knew that influenza was in Montreal. Dozens died. Among them was the Huron leader Kondiaronk, a famed orator who had, more than any other, convened the gathering as a last-ditch effort to avoid internecine conflict. His body was placed on a bed of beaver pelts, covered by a scarlet cloth, and surrounded by a copper pot, a rifle, and a sword. In their diversity, the objects symbolized the peaceful mixing of cultures that Kondiaronk hoped lay in the future.

Nobody knows how many died during the pandemics of the 1770s and 1780s, but even if one had a number it wouldn’t begin to tally the impact. Disease turned whole societies to ash. Six Cree groups in western Canada disappeared after 1781; the Blackfoot nation, blasted by smallpox, sent peace emissaries to Shoshone bands, only to find that all had vanished. “The country to the south was empty and silent,” Calloway wrote. So broken were the Omaha by disease that according to tradition they launched a deliberately suicidal attack against their enemies. Those who did not die quit their villages and became homeless wanderers.

Cultures are like books, the anthropologist Claude Lévi-Strauss once remarked, each a volume in the great library of humankind. In the sixteenth century, more books were burned than ever before or since. How many Homers vanished? How many Hesiods? What great works of painting, sculpture, architecture, and music vanished or never were created? Languages, prayers, dreams, habits, and hopes—all gone. And not just once, but over and over again. In our antibiotic era, how can we imagine what it means to have entire ways of life hiss away like steam? How can one assay the total impact of the unprecedented calamity that gave rise to the world we live in? It seems important to try. I would submit that the best way to come near to encompassing the scale and kind of the loss, and its causes, is to look at the single case where the intellectual life of a Native American society is almost as well documented as its destruction.

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