by Carl Zimmer
Unfortunately, we can expect more of that sort of weather in the future. Carbon dioxide and other heat-trapping gases are raising the average temperature in the United States, and climate scientists project that the temperature will continue to rise much higher in decades to come. Now that West Nile virus has made a new home here, we’re making that home more comfortable.
Predicting the Next Plague
Severe Acute Respiratory Syndrome and Ebola
A hunter emerges from a tropical forest, a shotgun in one hand, the carcass of a monkey in the other. He walks into a village in the southeast corner of Cameroon. It’s a scene that replays itself every day in villages, not just in Africa, but around the world. Hunters kill wild animals and bring them home to feed their families or to sell for cash. But on this day, the scene ends with a twist. The hunter hands over the monkey to his wife to butcher. As she cuts up the monkey, she stops to hold a dismembered leg over a piece of paper marked with five circles. Drops of blood fill one circle after another. The hunter’s wife then slips the sheet of paper in a Ziploc bag and hands it to a team of scientists who have paid her a visit. The scientist, who belongs to an organization called the Global Viral Forecasting Initiative, will analyze the blood-soaked paper for viruses infecting the monkey.
The Global Viral Forecasting Initiative is trying to change the way we fight viruses. Someday, somewhere, a virus we don’t know about is going to emerge as a major new threat to human health. We’ve seen it happen many times before, and so we know it will happen again. GVFI scientists think we’ll do a better job fighting that new virus if we can learn something about it in advance. To eliminate the advantage of surprise, GVFI scientists are looking for these viruses before they jump into humans. The best place to look for them is in animals, such as the monkeys that Cameroonian hunters kill for food.
The threat of new viruses has inspired a string of cheesy Hollywood movies over the years. In The Andromeda Strain, which came out in 1971, a satellite falls to Earth with an extraterrestrial virus that threatens to wipe out humanity. In the 1995 movie Outbreak, a monkey imported from Africa spreads a deadly virus through a California town, which the Army wants to bomb to prevent it from spreading across the country. And in 28 Days Later, released in 2002, a virus sweeps through London, turning its victims into homicidal maniacs.
The reality of new viruses is nothing like these fantasies. In its own way, it’s far more frightening. Over the course of human history, many viruses have made the evolutionary leap from animal hosts to our own species. And just over the past century, dozens of viruses have made this transition, giving rise to new diseases. Scientists have found that these new viruses have generally taken the same route into our species. It’s likely that they will take the same path in the future.
Many human viruses evolved from ancestral pathogens that were well adapted to living in other species. For example, HIV evolved from a virus found in chimpanzees known as SIVcpz. For centuries, the virus moved from chimpanzee to chimpanzee, infecting immune cells and slowly eroding their defenses. In the early 1900s, some of the viruses moved from chimpanzees to humans, evolving into HIV. The most HIV-like strains of SIVcpz are carried by chimpanzees that live in the forests in Cameroon. It was there that the virus likely made the transition. Both SIVcpz and HIV are spread through blood-to-blood contact. SIVcpz probably first infected the hunters who killed chimpanzees for meat. The virus-laden blood in the butchered apes made contact with cuts on the hunters, delivering SIVcpz into new hosts.
When animal viruses first make contact with humans, they only use them as what scientists called “spillover hosts.” Adapted to growing in other animals, the viruses can only grow slowly in humans and typically fail to spread from one human to another. When SIVcpz started infecting hunters, it probably still depended on chimpanzees to replenish its numbers. But the viruses were also mutating rapidly, and mutant SIVcpz eventually evolved the ability to survive in humans and spread from one human to the next.
Initially, new human viruses only cause local outbreaks, because they still can’t move between people very well. After each human epidemic sputters to an end, the virus still thrives in its animal host. But as the virus spends more time in humans, natural selection favors mutations that adapt them to their new host. The epidemics in humans get bigger and last longer. HIV, for example, thrived as African colonies grew and networks of roads linked forest villages to large cities where the virus could circulate among many people. As HIV became better adapted to infecting humans, it lost its ability to attack chimpanzees.
No one knew about the transformation of HIV while it was happening. Only in the early 1980s, sixty years or so after the virus had crossed into our species, did scientists finally isolate the virus and realize it was causing AIDS. By then, HIV was well established in our species and started to become one of the worst diseases in human history. We can only speculate about how much easier it would have been to fight the disease back when it was infecting just a few hundred villagers in Cameroon.
In recent years, scientists have been able to identify new human diseases far faster. In November 2002, for example, a Chinese farmer came to a hospital suffering from a high fever and died soon afterward. Other people from the same region of China began to develop the disease as well, but it didn’t reach the world’s attention until an American businessman flying back from China developed a fever on a flight to Singapore. The flight stopped in Hanoi, where the businessman died. Soon, people were falling ill in countries around the world, although most of the cases turned up in China and Hong Kong. About 10 percent of people who became sick died in a matter of days. The disease was not one that any doctor had identified before—not the flu, not pneumonia, nor any other known disease. It was dubbed severe acute respiratory syndrome, or SARS.
Scientists began searching samples from SARS victims for a cause of the diseases. Malik Peiris of the University of Hong Kong led the team of researchers who found it. In a study of fifty patients with SARS, they discovered a virus growing in two of them. The virus belonged to a group of species called coronaviruses, which can cause colds and the stomach flu. Peiris and his colleagues sequenced the genetic material in the new virus and then searched for matching genes in the other patients. They found a match in forty-five of them.
Based on their experience with viruses such as HIV, scientists suspected that the SARS virus had evolved from a virus that infects animals. They began to analyze viruses in animals with which people in China have regular contact. As they discovered new viruses, they added their branches to the SARS evolutionary tree. In a matter of months, scientists had reconstructed the history of SARS.
The virus started in Chinese bats. A lineage of the viruses then began to spill over into a catlike mammal called a civet. Civets are a common sight in Chinese animal markets, and it’s likely that humans became spillover hosts as well. The virus then evolved the ability to leap from human to human. SARS was a very young virus when scientists discovered it, and the speed at which it was discovered helped make it a relatively small outbreak. Scientists were able to identify and quarantine people with the disease, and they banned the sale of civets in markets. Although the SARS virus managed to spread across much of the world, it only caused about eight thousand cases and nine hundred deaths before it disappeared.
We can expect more viruses to sweep into our species, and they will probably come at an accelerating pace. Animals in remote parts of the world have harbored exotic viruses for millions of years, and for all that time humans have had little contact with them. Now humans are moving deep into these remote territories to harvest timber, dig mines, and establish new farms. And in the process, they’ve come into contact with new viruses. Nipah virus, for example, causes dangerous inflammation of the brain in its victims in Southeast Asia. It’s a virus that normally lives in bats, which once lived far from humans in jungles. Now the bats—and the viruses—have no jungles to live in.
There’s no reason to think that
one of these new viruses will wipe out the human race. That may be the impression that movies like The Andromeda Strain give, but the biology of real viruses suggests otherwise. Ebola, for example, is a horrific virus that can cause people to bleed from all their orifices, including their eyes. It can sweep from victim to victim, killing almost all its hosts along the way. And yet a typical Ebola outbreak only kills a few dozen people before coming to a halt. The virus is just too good at making people sick, and so it kills its victims faster than it can find new ones. Once an Ebola outbreak ends, the virus vanishes for years.
Ebola-like viruses may be frightening, but they probably pose less of a danger to our species than viruses with a lower death rate that can spread to more hosts. The 1918 outbreak of influenza killed only a tiny fraction of its victims. But because it infected one in three people on Earth, that tiny fraction added up to an estimated fifty million people. HIV crept slowly and surreptitiously around the planet before it was first detected. Instead of causing the terrifying symptoms of Ebola, HIV quietly breaks down the immune system over the course of many years.
We don’t know which virus will create the next great epidemic, in part because we don’t know the world of viruses very well. GVFI scientists have discovered a number of new viruses in African monkeys. Their tests on hunters have revealed those viruses in humans as well. Fortunately, these new viruses cannot yet spread from person to person. But that doesn’t mean that we can simply ignore them. Just the opposite: these are the viruses we need to block before they get a chance to make the great leap into our species.
The Long Goodbye
Smallpox
We humans are good at creating new viruses by accident—whether it’s a new flu virus concocted on a pig farm, or HIV evolving from the viruses of butchered chimpanzees. What we’re not so good at is getting rid of viruses. Despite all the vaccines, antiviral drugs, and public health strategies at our disposal, viruses still manage to escape annihilation. The best we can typically manage is to reduce the harm viruses cause. HIV infections, for example, have declined in the United States, but fifty thousand Americans still acquire the virus every year. Vaccination programs have eliminated some viruses from some countries, but the viruses can still thrive in other parts of the world. In fact, modern medicine has only managed to completely eradicate a single species of human virus from nature. The distinction goes to the virus that causes smallpox.
But what a virus to wipe out. Over the past three thousand years, smallpox may have killed more people than any other disease on Earth. Ancient physicians were well aware of smallpox, because its symptoms were so clear and distinct. A victim became infected when the virus slipped into the airway. After a week or so, the infection brought chills, a blazing fever, and agonizing aches. The fever ebbed after a few days, but the virus was far from done. Red spots developed inside the mouth, then the face, and then over the rest of the body. The spots filled with pus and caused stabbing pain. About a third of people who got smallpox eventually died. In the survivors, scabs covered over the pustules, which left behind deep, permanent scars.
Some thirty-five hundred years ago, smallpox left its first recorded trace on humanity: three mummies from ancient Egypt, studded with pustules. Many of the oldest centers of civilization in the Old World, from China to India to ancient Greece, felt the wrath of the virus. In 430 BC, an epidemic of smallpox swept through Athens, killing a quarter of the Athenian army and a large percentage of the city’s population. In the Middle Ages, crusaders returning from the Middle East brought smallpox to Europe. Each time the virus arrived in a new defenseless population, the effects were devastating. In 1241 smallpox first came to Iceland, where it promptly killed twenty thousand of the island’s seventy thousand inhabitants. Smallpox became well established in the Old World as cities grew, providing a high density of potential hosts. Between 1400 and 1800, smallpox killed an estimated five hundred million people every century in Europe alone. Its victims included sovereigns such as Czar Peter II of Russia, Queen Mary II of England, and Emperor Joseph I of Austria.
It was not until Columbus’s arrival in the New World that Native Americans got their first exposure to the virus. The Europeans unwittingly brought a biological weapon with them that gave the invaders a brutal advantage over their opponents. With no immunity whatsoever to smallpox, Native Americans died in droves when they were exposed to the virus. In Central America, over 90 percent of the native population is believed to have died of smallpox in the decades following the arrival of the Spanish conquistadores in the early 1500s.
The first effective way to prevent the spread of smallpox probably arose in China around AD 900. A physician would rub a scab from a smallpox victim into a scratch in the skin of a healthy person. (Sometimes they administered it as an inhaled powder instead.) Variolation, as this process came to be called, typically caused just a single pustule to form on the inoculated arm. Once the pustule scabbed over, a variolated person became immune to smallpox.
At least, that was the idea. Fairly often, variolation would trigger more pustules, and in 2 percent of cases, people died. Still, a 2 percent risk was more attractive than the 30 percent risk of dying from a full-blown case of smallpox. Variolation spread across Asia, moving west along trade routes until the practice came to Constantinople in the 1600s. As news of its success traveled into Europe, physicians there began to practice variolation as well. The practice triggered religious objections that only God should decide who survived the dreaded smallpox. To counteract these suspicions, doctors organized public experiments. Zabdiel Boylston, a Boston doctor, publicly variolated hundreds of people in 1721 during a smallpox epidemic; those who had been variolated survived the epidemic in greater numbers than those who had not been part of the trial.
No one at the time knew why variolation worked, because nobody knew what viruses were or how our immune systems fought them. The treatment of smallpox moved forward mainly by trial and error. In the late 1700s, the British physician Edward Jenner invented a safer smallpox vaccine based on stories he heard about how milkmaids never got smallpox. Cows can get infected with cowpox, a close relative of smallpox, and so Jenner wondered if it provided some protection. He took pus from the hand of a milkmaid named Sarah Nelmes and inoculated it into the arm of a boy. The boy developed a few small pustules, but otherwise he suffered no symptoms. Six weeks later, Jenner variolated the boy—in other words, he exposed the boy to smallpox, rather than cowpox. The boy developed no pustules at all. Jenner published a pamphlet in 1798 documenting this new, safer way to prevent smallpox. He dubbed it “vaccination,” after the Latin name of cowpox, Variolae vaccinae. Within three years, over one hundred thousand people in England had gotten vaccinated against smallpox, and vaccinations spread around the world. In later years, other scientists borrowed Jenner’s techniques and invented vaccines for other viruses. From rumors about milkmaids came a medical revolution.
As vaccines grew popular, doctors struggled to keep up with the demand. At first they would pick off the scabs that formed on vaccinated arms, and use them to vaccinate others in turn. But since cowpox occurred naturally only in Europe, people in other parts of the world could not simply acquire the virus themselves. In 1803, King Carlos of Spain came up with a radical solution: a vaccine expedition to the Americas and Asia. Twenty orphans boarded a ship in Spain. One of the orphans had been vaccinated before the ship set sail. After eight days, the orphan developed pustules, and then scabs. Those scabs were used to vaccinate another orphan, and so on through a chain of vaccination. As the ship stopped in port after port, the expedition delivered scabs to vaccinate the local population.
Physicians struggled throughout the 1800s to find a better way to deliver smallpox vaccines. Some turned calves into vaccine factories, infecting them repeatedly with cowpox. Some experimented with preserving the scabs in fluids like glycerol. It wasn’t until scientists finally worked out the nature of smallpox and cowpox—the fact that they were viruses—that it became possible
to develop a vaccine that could be made on an industrial scale and shipped around the world.
Once vaccines became common, smallpox began to lose its fierce grip on humanity. Through the early 1900s, one country after another recorded their last case of smallpox. By 1959, smallpox had retreated from Europe, the Soviet Union, and North America. It remained a scourge of tropical countries with poor medical systems in place. But it was beaten so far back that some public health workers began to contemplate an audacious goal: eliminating smallpox from the planet altogether.
The advocates of smallpox eradication built their case on the biology of the virus. Smallpox only infects humans, not animals. If it could be systematically eliminated from every human population, there would be no need to worry that it was lurking in pigs or ducks, waiting to reinfect us. What’s more, smallpox is an obvious disease. Unlike a virus like HIV, which can take years to make itself known, smallpox declares its gruesome presence in a matter of days. Public health workers would be able to identify outbreaks and track them with great precision.
Yet the idea of eradicating smallpox met with intense skepticism. If everything went exactly according to plan, an eradication project would require years of labor by thousands of trained workers, spread across much of the world, toiling in many remote, dangerous place. Public health workers had already tried to eradicate other diseases, like malaria, and failed.