There are many poxviruses in nature, and they infect species that gather in swarms and herds, circulating among them like pickpockets at a fair. There are two principal kinds of poxviruses: the poxes of vertebrates and the poxes of insects. Pox hunters have so far discovered mousepox, monkeypox, skunkpox, pigpox, goatpox, camelpox, cowpox, pseudo-cowpox, buffalopox, gerbilpox, several deerpoxes, chamoispox, a couple of sealpoxes, turkeypox, canarypox, pigeonpox, starlingpox, peacockpox, sparrowpox, juncopox, mynahpox, quailpox, parrotpox, and toadpox. There’s mongolian horsepox, a pox called Yaba monkey tumor, and a pox called orf. There’s dolphinpox, penguinpox, two kangaroopoxes, raccoonpox, and quokkapox. (The quokka is an Australian wallaby.) Snakes catch snakepox, spectacled caimans suffer from spectacled caimanpox, and crocodiles get crocpox. “Generally speaking, when crocodiles get crocpox, you see these bumps on them. I don’t think it’s particularly nasty for a croc,” a poxvirus expert named Richard Moyer said to me. “My guess is that fish get poxes, but nobody’s looked much for fish with pox,” Moyer said.
Insects are tortured by poxviruses. There are three groups of insect poxviruses: the beetlepoxes, the butterflypoxes (which include the mothpoxes), and the poxes of flies, including the mosquitopoxes. Any attempt to get to the bottom of the insect poxes would be like trying to enumerate the nine billion names of God.
Insects don’t have skin—they have exoskeletons—and so they can’t pustulate. Instead, poxviruses drive insects mad. A caterpillar that has caught a pox becomes nervous. It staggers around in circles on a leaf, agitated and losing its balance, and it can’t seem to find its way. (This may be a caterpillar’s version of “the anxious face of smallpox.”) The caterpillar’s development is interrupted, and the caterpillar keeps on growing bigger, until it is twice normal size. The virus is making its host larger—a nice way for a virus to amplify itself. Eventually the insect is transformed and destroyed, ending up as a swollen bag filled with a soup of insect guts and tiny crystalline nuggets that look like Wiffle balls. This soup is technically known as a virus melt. Each opening of each Wiffle ball in the melt ends up containing a particle of insect pox. The insect pox virions are inserted into the Wiffle balls and protrude from them like the knobs on a mine.
The caterpillar dies clinging to a leaf, and splits open, and out pours a spreading virus melt. The guts decay and are gone, leaving behind the Wiffle balls, which can persist for years in the environment. One day, a caterpillar comes along and eats the viral equivalent of a land mine, and melts down, and so it goes for hundreds of millions of years in the happy life of an insect pox.
No fossils of viruses have ever been found in rocks, so the origin of viruses is shrouded in mystery. Viruses are presumably very ancient, and may be similar to the earliest forms of life that appeared on the earth more than three and a half billion years ago. The insect poxes may have arisen in early Devonian times, long before the age of dinosaurs, when the seas teemed with sharks and armored fish, and the earth was covered with mosses and small plants, and there were still no trees, and the first insects were evolving. Some experts feel that the poxes of vertebrates could be the descendants of insect poxes. Smallpox, too, looks like the knobs on the Wiffle ball, though without the ball. Perhaps there was a trans-species jump of an insect pox into a newt some three hundred and fifty million years ago. Perhaps the knobs fell off the Wiffle ball when the pox got into the newt, and we are living with the consequences today.
At least two known midgepoxes torment midges. Grasshoppers are known to suffer from at least six different grasshopperpoxes. If a plague of African locusts breaks out with locustpox, the plague is hit with a plague, and is in deep trouble. Poxviruses keep herds and swarms of living things in check, preventing them from growing too large and overwhelming their habitats. Viruses are an essential part of nature. If all the viruses on the planet were to disappear, a global catastrophe would ensue, and the natural ecosystems of the earth would collapse in a spectacular crash under burgeoning populations of insects. Viruses are nature’s crowd control, and a poxvirus can thin a crowd in a hurry. For most of human history, the human species consisted of small, scattered groups of hunter-gatherers. The human species did not collect in crowds, and so it was almost beneath the notice of a pox.
With the growth of agriculture, the human population of the earth swelled and became more tightly packed. Villages grew into towns, and towns grew into cities, and people began to live in crowds in river valleys where the land was fertile. At that point, the human species became an accident with a poxvirus waiting to happen.
Epidemiologists have done some mathematics on the spread of smallpox, and they’ve found that the virus needs a population of around two hundred thousand people living within fourteen days of travel from one another or the virus can’t keep its life cycle going, and it dies out. Those conditions did not occur until the appearance of settled agricultural areas and cities, about seven thousand years ago. Smallpox could be described as the first urban virus.
The virus’s genes suggest that it was once a rodent virus. Smallpox might once have lived in a rodent that multiplied in storage bins of grain. Perhaps, perhaps not. Smallpox might be a former pox of mice, or it might be a ratpox that moved on. Maybe, maybe not. There is, however, a strong suspicion that smallpox made its trans-species jump into humans in one of the early agricultural river valleys—perhaps in the valley of the Nile, or along the Tigris and Euphrates in Mesopotamia, or in the Indus River valley, or possibly along the rivers in China. By 400 B.C., the population of China had grown to twenty-five million people, which was probably the largest and densest collection of people at that time, and they were crowded along the Yellow River and the Yangtze. Down by the river somewhere, the pox found its human lover.
The mummy of the Pharaoh Ramses V, who died suddenly as a young man in 1157 B.C., lies inside a glass case in the Cairo Museum. His body is speckled with yellow blisters on his face, forearms, and scrotum. It looks like a centrifugal rash. Pox experts would very much like to look at the soles of the pharaoh’s feet and the palms of his hands, to see if there are any blisters on them, for that would be a sharp diagnostic sign of smallpox. But the pharaoh’s feet are wrapped in cloth, and his hands are crossed over his chest, palms downward, and the authorities at the Cairo Museum will not allow anyone to move them. Pox experts would also like to clip out a bit of the pharaoh’s skin and test it for the DNA of smallpox virus, but so far that has not been allowed either.
Another possibility for the point of contact between humans and variola is Southeast Asia around 1000 B.C. Crowded city-states were developing there. Or the original host of smallpox may have been an African squirrel that lived in a crescent of green forests that are thought to have once existed along the southern reaches of the Nile River. The climate dried out, the forests disappeared or were cut down by people, the country turned into grasslands, and the squirrel became extinct. Variola moved on.
It is possible that variola caused the plague of Athens in 430 B.C., which killed Pericles and dealt the city a devastating blow during the opening years of the Peloponnesian War with Sparta. Variola may have caused the Antonine Plague in Rome, which seems to have been carried home by Roman legions who fought in Syria in A.D. 164. Certainly smallpox rooted itself early in people living in the river valleys of China. The Chinese worshiped a goddess of smallpox named T’ou-Shen Niang-Niang, who could cure the disease. There was another goddess, Pan-chen, to whom people prayed if a victim’s skin began to darken with black pox. In A.D. 340, the great Chinese medical doctor Ko Hung gave an exact description of smallpox. He believed that the disease had first come to China “from the west,” about three hundred years before his lifetime.
Variola may have caused a decline in the human population of Italy during the later years of the Roman empire, making the empire more vulnerable to collapse under barbarian attacks. (The population of Italy in late Roman times may also have been gutted by malaria, or perhaps by a double whammy of malaria plus
smallpox.) Variola dwelled along the Ganges River in India for at least the past two thousand years. The Hindu religion has a goddess of smallpox, named Shitala Ma, and there are temples in her honor all over India. (Ma means the same in Hindi as it does in English—“mother.”) It is hard to say whether Shitala Ma is a good goddess or a bad one, but you certainly do not want to make her mad. In ancient Japan, smallpox arrived once in a while from China and Korea, but the virus couldn’t start a chain of transmission there because the population was too thin. Eventually, around A.D. 1000, the population in Japan reached four and a half million, and apparently two hundred thousand people began to live within about two weeks’ travel from one another; smallpox came to live with them, and they came to think of smallpox as a demon. In A.D. 910, the Persian physician al-Razi (Rhazes) saw a lot of smallpox when he was the medical director of the Baghdad hospital. Ancient sub-Saharan Africa had a relatively scattered human population and remained largely free of smallpox, except for occasional outbreaks along the coasts, triggered by the comings and goings of traders and slavers. The more concentrated the human population, the more likely it was to be thinned regularly by variola.
In 1520, Captain Pánfilo de Narváez landed on the east coast of what is now Mexico, near Vera Cruz. His plan was to investigate the Aztec empire, which was centered in great and powerful inland cities. One of the members of Captain Narváez’s landing party was an African slave who was sick with smallpox. Variola hatched from tiny spots in the man’s mouth and amplified itself into a biological shockwave that ran from the seacoast back into the Aztec empire, ultimately killing roughly half of the human population of Mexico. The wave of death that came out of less than a square inch of membrane in the mouth of Captain Narváez’s man went through Central America, and it boomed along the spine of the Andes, where it gobsmacked the Inca empire. By the time the Spanish conquerors entered Peru, smallpox had softened the place up, and had killed so many people that the armies of the Incas had trouble putting up effective resistance. Smallpox had reduced the population of the Western Hemisphere while showing itself to be the most powerful de facto biological weapon the world has yet seen. (Measles was also lethal in Native American populations, and it worked alongside variola in the Americas.) During the French and Indian War, when Chief Pontiac of the Ottawa tribes was leading a siege against the British at Fort Detroit in 1763, Sir Jeffrey Amherst, the head of the British forces, wrote a letter to one of his field officers, Colonel Henry Bouquet: “Could it not be contrived to send smallpox among these disaffected tribes of Indians?” Amherst asked. “We must on this occasion use every stratagem in our power to reduce them.”
Colonel Bouquet got the idea of the stratagem quite well, and his reply was to the point: “I will try to inoculate the [buggers] with some blankets that may fall into their hands.” Not long afterward, one Captain Ecuyer, a British soldier, wrote in his journal: “Out of our regard for [two visiting chiefs] we gave them two blankets and a handkerchief out of the smallpox hospital. I hope it will have the desired effect.” It did, and smallpox subsequently burned through the human population of the Ohio River valley, killing considerable numbers of Native Americans. This was strategic biological warfare, and it worked well, at least from the English point of view.
Vision
IN THE LATE seventeen hundreds, the English country doctor Edward Jenner noticed that dairymaids who had contracted cowpox seemed to be protected from smallpox, and he decided to try an experiment. On May 14th, 1796, Jenner scratched the arm of a boy named James Phipps, introducing into his skin a droplet of cowpox pus that he had scraped from a blister on the hand of Sarah Nelmes, a dairy worker. He called this pus “the Vaccine Virus”—the word vaccine is derived from the Latin word for cow. The boy developed a single pustule on his arm, and it healed rapidly. A few months later, Jenner scratched the boy’s arm with lethal infective pus that he had taken from a smallpox patient—today, this is called a challenge trial. The boy did not come down with smallpox. Edward Jenner had discovered and named vaccination—the practice of infecting a person with a mild or harmless virus in order to strengthen his or her immunity to a similar disease-causing virus. “It now becomes too manifest to admit of controversy, that the annihilation of the Small Pox, the most dreadful scourge of the human species, must be the final result of this practice,” Jenner wrote in 1801.
IN 1965, Donald Ainslie Henderson was thirty-six years old and was the head of disease surveillance at the Centers for Disease Control in Atlanta, when he wrote a proposal for the eradication of smallpox in west Africa. In common with most medical authorities at the time, he didn’t believe that smallpox or any other infectious disease could be eradicated from the planet, but he thought that perhaps it could be done in a region. Somehow, his proposal ended up at the White House and had an effect there. For years, the Soviets had been getting up at meetings of the World Health Assembly—the international body that approves the WHO’s programs—and demanding the global eradication of smallpox, and now Lyndon Johnson decided to endorse the idea. It was a political move to help improve Soviet-American relations. Henderson was abruptly called to Washington to meet with a top official in the U.S. Public Health Service, James Watts, who informed him that he was going to WHO headquarters in Geneva to put together such a program.
“What if I don’t want to go?”
“You’re ordered to go,” Watts said.
“Suppose I refuse?”
“Then you will resign from government service.”
Henderson assumed that the attempt to eradicate smallpox would fail in about eighteen months. He told his wife, Nana, and their three children that they were going to stay in Geneva for a little while, until the program fell apart and they could come home. They put most of their things in storage in Atlanta and arrived in Geneva on the first of November. The Henderson family settled into a bungalow near Lake Geneva, not very far from the town where variola had been given its official name in A.D. 580, and they rented a refrigerator, since D.A. felt they weren’t going to be there long. They would not see their stored things for another twelve years.
The Eradication program was built on the idea that variola has one great weakness: it is able to replicate only inside the human body. People have become its only natural host. Wherever it had come from in nature, it had actually lost the ability to infect its original host, and indeed, perhaps its original host had gone extinct. Variola had no reservoir of hosts in nature in which it could hide and continue to cycle if there was an attempt to eradicate it from people.
When people were infected with vaccinia, the mild cousin of smallpox, their immune systems became able to recognize variola and fight it off. If the human species could be widely infected with vaccinia and in just the right way, then vaccinia could, in effect, supplant variola in the human host. Driven out of its host by rival vaccinia, variola would have no niche left in the ecosystems of the earth.
This was, in fact, a daring plan, since no one could claim to understand the structure of natural ecosystems, especially in microbiology, or to have a clue as to whether the strategy would really work. Nature is full of surprises. Henderson wondered, for example, if smallpox just might have a little unnoticed reservoir somewhere in rodents. If so, that would destroy the dream of eradication, for humans have never been any good at getting rid of rodents. Henderson asked a virologist named James Steele if he thought any animal anywhere could harbor smallpox. Steele answered emphatically, “No. You will not find an animal reservoir.” Henderson couldn’t quite believe this, and for years the eradicators searched the world for a rodent, a bird, a lizard, a newt, anything with variola. They found no animal carrier of smallpox. Variola could not even replicate in primates, the closest relatives of humans. But then, in 1968, to the surprise of the eradicators, a previously unknown virus called monkeypox was discovered in a group of captive monkeys in Copenhagen, and the virus was traced back to the African rain forest, where to this day monkeypox infects humans. Monkeypox is an
emerging virus that is making trans-species jumps into people in smoldering outbreaks in the rain forests of the Congo. Monkeypox may or may not one day take the natural place of smallpox vis-à-vis the human species.
Despite the evident fact that smallpox was restricted to a single host—people—many leading biologists believed that the eradication of any virus was a hopeless task. They held the opinion that it was impossible to separate a wild microbe from the ecological web it lived in. This view was expressed in 1965 by the evolutionary biologist René Dubos, in his book Man Adapting. “Even if genuine eradication of a pathogen or virus on a worldwide scale were theoretically and practically possible,” Dubos wrote, “the enormous effort required for reaching the goal would probably make the attempt economically and humanly unwise.” His belief was sensible and rational, it was held by most biologists of the time—and it was wrong.
When the program began, the World Health Assembly set a deadline of ten years for its completion. “President Kennedy had said we could land a man on the moon in ten years,” Henderson said, and so it should be possible to wipe out variola in the same amount of time. At first, the leaders of the Smallpox Eradication Program weren’t sure how to go about the job. They set a goal of vaccinating eighty percent of the population of countries that harbored smallpox, but that proved to be virtually impossible. They also developed the surveillance-and-ring-vaccination containment method. They tracked outbreaks of smallpox and swooped in and vaccinated everyone in a ring around the outbreak (as they would do in Meschede in 1970), which broke the chains of transmission and snuffed out the virus in that spot.