THE GENETICS OF VULNERABILITY
In August 1967 a missionary’s two-year-old daughter came down with measles in a village on the Toototobi River in Brazil, near the border with Venezuela. She and her family had just returned from the Amazonian city of Manaus and had been checked and cleared by Brazilian doctors before departure. Nonetheless the distinctive spots of measles emerged a few days after the family’s arrival on the Toototobi. The village, like many others in the region, was populated mainly by Yanomami Indians, a forest society on the Brazil-Venezuela border that is among the least Westernized on earth. They had never before encountered the measles virus. More than 150 Yanomami were in the village at the time. Most or all caught the disease. Seventeen died despite the horrified missionaries’ best efforts. And the virus escaped and spread throughout the Yanomami heartland, carried by people who did not know they had been exposed.
Partly by happenstance, the U.S. geneticist James Neel and the U.S. anthropologist Napoleon Chagnon flew into Yanomami country in the midst of the epidemic. Neel, who had long been worried about measles, was carrying several thousand doses of vaccine. Alas, the disease had preceded them. They frantically tried to create an epidemiological “firebreak” by vaccinating ahead of the disease. Despite their efforts, the affected villages had a mean death rate of 8.8 percent. Almost one out of ten people died from a sickness that in Western societies was just a childhood annoyance.
Later Neel concluded that the high death rate was in part due to grief and despair, rather than the virus itself. Still, the huge toll was historically unprecedented. The implication, implausible at first glance, was that Indians in their virgin-soil state were more vulnerable to European diseases than virgin-soil Europeans would have been. Perhaps surprisingly, there is some scientific evidence that Native Americans were for genetic reasons unusually susceptible to foreign microbes and viruses—one reason that researchers believe that pandemics of Dobynsian scale and lethality could have occurred.
Here I must make a distinction between two types of susceptibility. The first is the lack of acquired immunity—immunity gained from a previous exposure to a pathogen. People who have never had chicken pox are readily infected by the virus. After they come down with the disease, their immune system trains itself, so to speak, to fight off the virus, and they never catch it again, no matter how often they are exposed. Most Europeans of the day had been exposed to smallpox as children, and those who didn’t die were immune. Smallpox and other European diseases didn’t exist in the Americas, and so every Indian was susceptible to them in this way.
In addition to having no acquired immunity (the first kind of vulnerability), the inhabitants of the Americas had immune systems that some researchers believe were much more restricted than European immune systems. If these scientists are correct, Indians as a group had less innate ability to defend themselves against epidemic disease (the second kind of vulnerability). The combination was devastating.
The second type of vulnerability stems from a quirk of history. Archaeologists dispute the timing and manner of Indians’ arrival in the Americas, but almost all researchers believe that the initial number of newcomers must have been small. Their gene pool was correspondingly restricted, which meant that Indian biochemistry was and is unusually homogeneous. More than nine out of ten Native Americans—and almost all South American Indians—have type O blood, for example, whereas Europeans are more evenly split between types O and A.
Evolutionarily speaking, genetic homogeneity by itself is neither good nor bad. It can be beneficial if it means that a population lacks deleterious genes. In 1491, the Americas were apparently free or almost free of cystic fibrosis, Huntington’s chorea, newborn anemia, schizophrenia, asthma, and (possibly) juvenile diabetes, all of which have some genetic component. Here a limited gene pool may have spared Indians great suffering.
Genetic homogeneity can be problematic, too. In the 1960s and 1970s Francis L. Black, a virologist at Yale, conducted safety and efficacy tests among South American Indians of a new, improved measles vaccine. During the tests he drew blood samples from the people he vaccinated, which he later examined in the laboratory. When I telephoned Black, he told me that the results were “thought-provoking.” Every individual person’s immune system responded robustly to the vaccine. But the native population as a whole had a “very limited spectrum of responses.” And that, he said, “could be a real problem in the right circumstances.” For Indians, those circumstances arrived with Columbus.
Black was speaking of human leukocyte antigens (HLAs), molecules inside most human cells that are key to one of the body’s two main means of defense. Cells of all sorts are commonly likened to biochemical factories, busy ferments in which dozens of mechanisms are working away in complex sequences that are half Rube Goldberg, half ballet. Like well-run factories, cells are thrifty; part of the cellular machinery chops up and reuses anything that is floating around inside, including bits of the cell and foreign invaders such as viruses. Not all of the cut-up pieces are recycled. Some are passed on to HLAs, special molecules that transport the snippets to the surface of the cell.
Outside, prowling, are white blood cells—leukocytes, to researchers. Like minute scouts inspecting potential battle zones, leukocytes constantly scan cell walls for the little bits of stuff that HLAs have carried there, trying to spot anything that doesn’t belong. When a leukocyte spots an anomaly—a bit of virus, say—it destroys the infected or contaminated cell immediately. Which means that unless an HLA lugs an invading virus to where the leukocyte can notice it, that part of the immune system cannot know it exists, let alone attack it.
HLAs carry their burdens to the surface by fitting them into a kind of slot. If the snippet doesn’t fit into the slot, the HLA can’t transport it, and the rest of the immune system won’t be able to “see” it. All people have multiple types of HLA, which means that they can bring almost every potential problem to the attention of their leukocytes. Not every problem, though. No matter what his or her genetic endowment, no one person’s immune system has enough different HLAs to identify every strain of every virus. Some things will always escape notice. Imagine someone sneezing in a crowded elevator, releasing into the air ten variants of a rhinovirus, the kind of virus that causes the common cold. (Viruses mutate quickly and are commonly present in the body in multiple forms, each slightly different from the others.) For simplicity’s sake, suppose that the other elevator passengers inhale all ten versions of the virus. One man is lucky: he happens to have HLAs that can lock onto and carry pieces of all ten variants to the cell surface. Because his white blood cells can identify and destroy the infected cells, this man doesn’t get sick. Not so lucky is the woman next to him: she has a different set of HLAs, which are able to pick up and transport only eight of the ten varieties. The other two varieties escape the notice of her leukocytes and go on to give her a howling cold (eventually other immune mechanisms kick in and she recovers). These disparate outcomes illustrate the importance to a population of having multiple HLA profiles; one person’s HLAs may miss a particular bug, but another person may be equipped to combat it, and the population as a whole survives.
Most human groups are a scattershot mix of HLA profiles, which means that almost always some people in the group will not get sick when exposed to a particular pathogen. Indeed, if laboratory mice have too much HLA diversity, Black told me, researchers can’t use them to observe the progress of an infectious disease. “You get messy results—they don’t all get sick.” The opposite is true as well, he said. People with similar HLA profiles fall victim to the same diseases in the same way.
In the 1990s Black reviewed thirty-six studies of South American Indians. Not to his surprise, he discovered that overall Indians have fewer HLA types than populations from Europe, Asia, and Africa. European populations have at least thirty-five main HLA classes, whereas Indian groups have no more than seventeen. In addition, Native American HLA profiles are dominated by an unusually small number of types. About one third of South American Indians, Black discovered, have identical or near-identical HLA profiles; for Africans the figure is one in two hundred. In South America, he estimated, the minimum probability that a pathogen in one host will next encounter a host with a similar immune spectrum is about 28 percent; in Europe, the chance is less than 2 percent. As a result, Black argued, “people of the New World are unusually susceptible to diseases of the Old.” *11
Actually, some Old World populations were just as vulnerable as Native Americans to those diseases, and likely for the same reason. Indians’ closest genetic relatives are indigenous Siberians. They did not come into substantial contact with Europeans until the sixteenth century, when Russian fur merchants overturned their governments, established military outposts throughout the region, and demanded furs in tribute. In the train of the Russian fur market came Russian diseases, notably smallpox.
The parallels with the Indian experience are striking. In 1768 the virus struck Siberia’s Pacific coast, apparently for the first time. “No one knows how many have survived,” confessed the governor of Irkutsk, the Russian base on Lake Baikal, apparently because officials were afraid to travel to the affected area. A decade later, in 1779, the round-the-globe expedition of Captain James Cook reached Kamchatka, the long peninsula on the Pacific coast. The shoreline, the British discovered, was a cemetery. “We every where met with the Ruins of large Villages with no Traces left of them but the Foundation of the Houses,” lamented David Samwell, the ship’s surgeon. “The Russians told us that [the villages] were destroyed by the small Pox.” The explorer Martin Sauer, who visited Kamchatka five years after Cook’s expedition, discovered that the Russian government had at last ventured into the former epidemic zone. Scarcely one thousand natives remained on the peninsula, according to official figures; the disease had claimed more than five thousand lives. The tally cannot be taken as exact, but the fact remains: a single epidemic killed more than three of every four indigenous Siberians in that area.
After a few such experiences, the natives tried to fight back. “As soon as [indigenous Siberians] learn that smallpox or other contagious diseases are in town,” the political exile Heinrich von Füch wrote, “they set up sentries along all the roads, armed with bows and arrows, and they will not allow anyone to come into their settlements from town. Likewise, they will not accept Russian flour or other gifts, lest these be contaminated with smallpox.” Their efforts were in vain. Despite extreme precautions, disease cut down native Siberians again and again.
After learning about this sad history I again telephoned Francis Black. Being genetically determined, Indian HLA homogeneity cannot be changed (except by intermarriage with non-Indians). Did that mean that the epidemics were unavoidable? I asked. Suppose that the peoples of the Americas had, in some parallel world, understood the concept of contagion and been prepared to act on it. Could the mass death have been averted?
“There have been lots of cases where individual towns kept out epidemics,” Black said. During plague episodes, “medieval cities would barricade themselves behind their walls and kill people who tried to come in. But whole countries—that’s much harder. England has kept out rabies. That’s the biggest success story that comes to mind, offhand. But rabies is primarily an animal disease, which helps, because you only have to watch the ports—you don’t have many undocumented aliens sneaking in with sick dogs. And rabies is not highly contagious, so even if it slips through it is unlikely to spread.”
He stopped speaking for long enough that I asked him if he was still on the line.
“I’m trying to imagine how you would do it,” he said. “If Indians in Florida let in sick people, the effects could reach all the way up to here in Connecticut. So all these different groups would have had to coordinate the blockade together. And they’d have to do it for centuries—four hundred years—until the invention of vaccines. Naturally they’d want to trade, furs for knives, that kind of thing. But the trade would have to be conducted in antiseptic conditions.”
The Abenaki sent goods to Verrazzano on a rope strung from ship to shore, I said.
“You’d have to have the entire hemisphere doing that. And the Europeans would presumably have to cooperate, or most of them, anyway. I can’t imagine that happening, actually. Any of it.”
Did that mean the epidemics were inevitable and there was nothing to be done?
The authorities, he replied, could “try to maintain isolation, as I was saying. But that ends up being paternalistic and ineffective. Or they can endorse marriage and procreation with outsiders, which risks destroying the society they supposedly are trying to preserve. I’m not sure what I’d recommend. Except getting these communities some decent health care, which they almost never have.”
Except for death, he went on, nothing in medicine is inevitable. “But I don’t see how it [waves of epidemics from European diseases] could have been prevented for very long. That’s a terrible thought. But I’ve been working with highly contagious diseases for forty years, and I can tell you that in the long run it is almost impossible to keep them out.” *12