A Planet of Viruses - Carl Zimmer (2011)

THE VIRAL FUTURE

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.

The skeptics lost the debate, however, and in 1965, the World Health Organization launched the Intensified Smallpox Eradication Programme. The eradication effort was different in many ways from previous campaigns. It relied on a new prong-shaped needle that could deliver smallpox vaccine far more efficiently than regular syringes. As a result, vaccine supplies could be stretched much further than before. Public health workers also designed smart new strategies for administering vaccines. Trying to vaccinate entire countries was beyond the reach of the eradication project. Instead, public health workers identified outbreaks and took quick action to snuff them out. They quarantined victims and then vaccinated people in the surrounding villages and towns. The smallpox would spread like a forest fire, but soon it would hit the firebreak of vaccination and die out.

Outbreak by outbreak, the virus was beaten back, until the last case was recorded in Ethiopia in 1977. The world was now free of smallpox.

While the eradication campaign was a huge success, the smallpox virus had not disappeared completely. Scientists had established stocks of the virus in their laboratories to study. The WHO had all the stocks gathered up and deposited in two approved laboratories, one in the Siberian city of Novosibirsk in the Soviet Union, and one at the U.S. Centers for Disease Control and Prevention in Atlanta, Georgia. Smallpox experts could still study stocks from the two labs, but only under tight regulations. Most experts assumed that before long those last two collections of smallpox would be destroyed as well, and then the virus would become truly extinct.

It turns out, however, that there might actually be more smallpox virus in the world. In the 1990s, Soviet defectors revealed that their government had actually set up labs to produce a weaponized smallpox virus that could be loaded onto missiles and launched at enemy targets. After the fall of the Soviet government, the labs were abandoned. No one knows what ultimately happened to all the stocks of smallpox virus. We are left with the terrifying possibility that ex-Soviet virologists sold smallpox stocks to other governments or even terrorist organizations.

When these revelations emerged, some scientists and government officials decided the research stocks had to be preserved. Scientists could study them to help prepare for biological warfare. There remains much scientists don’t yet understand about smallpox. In recent years, scientists have started to decipher the strategies smallpox uses to fight the immune system. They have discovered an arsenal of weapons the virus deploys. Smallpox proteins can jam the signals the immune cells pass to each other to mobilize an attack, for example. Scientists have yet to figure out why smallpox is so deadly. Some researchers argue that the virus causes the immune system to attack a victim’s own body, rather than the virus. But that’s just a hypothesis still to be tested. Solving mysteries like these could conceivably lead to better vaccines, and even to antiviral drugs that might be effective against smallpox infections or other dangerous viruses that are equally deadly to humans.

In 2010, the WHO reopened the debate over whether to finally destroy the two remaining officially declared stocks smallpox in Russia and the United States. But now the debate has taken a twist that previous generations of smallpox fighters could never have dreamed of. Today scientists know the full genetic sequence of the smallpox virus. And they have the technology necessary to synthesize the smallpox genome from scratch. Synthesizing viruses is not the stuff of science fiction; scientists have already manufactured the genetic material of other viruses, like polio and the deadly 1918 influenza, and have used it to generate full-blown viruses.

There’s no evidence that anyone has tried to resurrect smallpox in the same way, but, then again, there’s no evidence that it would be impossible to do so. After thirty-five hundred years of suffering and puzzling over smallpox, we have finally figured it out. And yet, by understanding smallpox, we have ensured that it can never be utterly eradicated as a threat to humans. Our knowledge gives the virus its own kind of immortality.

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