A Planet of Viruses (2 page)

In 1879, Dutch farmers came to Adolph Mayer, a young agricultural chemist, to beg for help. Mayer carefully studied the scourge, which he dubbed tobacco mosaic disease. He investigated the environment in which the plants grew—the soil, the temperature, the sunlight. He could find nothing to distinguish the healthy plants from the sick ones. Perhaps, he thought, the plants were suffering from an invisible infection. Plant scientists had already demonstrated that fungi could infect potatoes and other plants, so Mayer looked for fungus on the tobacco plants. He found none. He looked for parasitic worms that might be infesting the leaves. Nothing.

Finally Mayer extracted the sap from sick plants and injected drops into healthy tobacco. The healthy plants, Mayer discovered,
turned sick as well. Some microscopic pathogen must be multiplying inside the plants. Mayer took sap from sick plants and incubated it in his laboratory. Colonies of bacteria began to grow and became large enough that Mayer could see them with his naked eye. Mayer applied the bacteria to healthy plants to see if it would trigger tobacco mosaic disease. It failed. And with that failure, Mayer’s research ground to a halt.

A few years later, another Dutch scientist named Martinus Beijerinck picked up where Mayer left off. He wondered if something other than bacteria was responsible for tobacco mosaic disease, something far smaller. He ground up diseased plants and passed the fluid through a fine filter that blocked both plant cells and bacteria. When he injected the clear fluid into healthy plants, they became sick.

Beijerinck filtered the juice from the newly infected plants and found that he could infect still more tobacco. Something in the sap of the infected plants—something smaller than bacteria— could replicate itself and could spread disease. Beijerinck called it a “contagious living fluid.”

Whatever that contagious living fluid carried was different from any other kind of life biologists knew about. It was not only inconceivably small but also remarkably tough. Beijerinck could add alcohol to the filtered fluid, and it would remain infective. Heating the fluid to near boiling did it no harm. Beijerinck soaked filter paper in the infectious sap and let it dry. Three months later, he could dip the paper in water and use the solution to sicken new plants.

Beijerinck used the word
virus
to describe the mysterious agent in his contagious living fluid. It was the first time anyone used the word the way we do today. But in a sense, Beijerinck simply used it to define viruses by what they were
not
. They were not animals, plants, fungi, or bacteria. What exactly they were, Beijerinck could not say. He had reached the limits of what nineteenth-century science could reveal.

A deeper understanding of viruses would have to wait for better tools and better ideas. Electron microscopes allowed scientists
to see viruses for what they are: particles of a nearly inconceivably small size. For comparison, tap out a single grain of salt from a shaker. You could line up about ten skin cells along one side of it. You could line up about a hundred bacteria. Compared to viruses, however, bacteria are giants. You could line up a thousand viruses alongside that same grain of salt.

Despite the small size of viruses, scientists discovered ways to dissect them and peer inside. A human cell is stuffed with millions of different molecules that it uses to sense its surroundings, crawl hither and yon, take in food, grow, and decide whether to divide in two or kill itself for the good of its fellow cells. Virologists found that many of the viruses they studied were just protein shells holding a few genes. They discovered that viruses can replicate themselves, despite their paltry genetic instructions, by hijacking other forms of life. They could see viruses inject their genes and proteins into a host cell, which they manipulated into producing new copies of the virus. One virus might go into a cell, and within a day a thousand viruses came out.

Virologists had grasped these fundamental facts by the 1950s. But virology did not come to a halt. For one thing, virologists knew little about the many different ways in which viruses make us sick. They didn’t know why papillomaviruses can cause horns to grow on rabbits and cause hundreds of thousands of cases of cervical cancer each year. They didn’t know what made some viruses deadly and others relatively harmless. They had yet to learn how viruses evade the defenses of their hosts and how they evolve faster than anything else on the planet. In the 1950s they did not know that a virus that would later be named HIV had already spread from chimpanzees into our own species, or that thirty years later it would become one of the greatest killers in history. They could not have dreamed of the vast numbers of viruses that exist on Earth; they could not have guessed that most of the genetic diversity of life can be found in virus genes. They did not know that viruses help produce much of the oxygen we breathe and help control the planet’s thermostat. And they certainly would not have guessed that the human genome is partly
composed from thousands of viruses that infected our distant ancestors, or that life as we know it may have gotten its start four billion years ago from viruses.

Now scientists know these things—or, to be more precise, they know
of
these things. They now recognize that from the Cave of Crystals to the inner world of the human body, this is a planet of viruses. Their understanding is still rough, but it is a start. So let us start as well.

Rhinovirus

Around 3,500 years ago, an Egyptian scholar sat down and wrote the oldest known medical text. Among the diseases he described in the so-called Ebers Papyrus was something called
resh
. Even with that strange sounding name, its symptoms—a cough and a flowing of mucus from the nose—are immediately familiar to us all.
Resh
is the common cold.

Some viruses are new to humanity. Other viruses are obscure and exotic. But human rhinoviruses—the chief cause of the common cold, as well as asthma attacks— are old, cosmopolitan companions. It’s been estimated that every human being will spend a year of his or her
life lying in bed, sick with colds. The human rhinovirus is, in other words, one of the most successful viruses of all.

Hippocrates, the ancient Greek physician, believed that colds were caused by an imbalance of the humors. Two thousand years later, the physiologist Leonard Hill argued in the 1920s that they were caused by walking outside in the morning, from warm to cold air. The first clue to the true cause of colds came when Walter Kruse, a German microbiologist, had a snuffly assistant blow his nose and mix the mucus into a salt solution. Kruse and his assistant purified the fluid through a filter and then put a few drops into the noses of twelve of their colleagues. Four of them came down with colds. Later, Kruse did the same thing to thirty-six students. Fifteen of them got sick. Kruse compared their outcomes to thirty-five people who didn’t get the drops. Only one of the drop-free individuals came down with a cold.

Kruse’s experiments made it clear that some tiny pathogen was responsible for the cold. At first, many experts believed it was some kind of bacteria, but Alphonse Dochez ruled that out in 1927. He filtered the mucus from people with colds, the same way Beijerinck had filtered tobacco plant sap thirty years before, and discovered that the bacteria-free fluid could make people sick. Only a virus could have slipped through Dochez’s filters.

It took another three decades before scientists figured out exactly which viruses had slipped through. Known as human rhinoviruses (
rhino
means nose), they are remarkably simple, with only ten genes apiece. (We have twenty thousand.) And yet that haiku of genetic information is enough to let the human rhinovirus invade our bodies, outwit our immune system, and give us colds.

The human rhinovirus spreads by making noses run. People with colds wipe their noses, get the virus on their hands, and then spread the virus onto door knobs and other surfaces they touch. The virus hitches onto the skin of other people who touch those surfaces and then slips into their body, usually though their nose. Rhinoviruses can invade the cells that line the interior of the nose, throat, or lungs. They trigger the cells to open up a trapdoor through which they slip. Over the next few hours, a rhinovirus will use its host cells to make copies of its genetic material and
protein shells to hold them. The host cell then rips apart, and the new virus escapes.

Rhinoviruses infect relatively few cells, causing little real harm. So why can they cause such miserable experiences? We have only ourselves to blame. Infected cells release special signaling molecules, called cytokines, which attract nearby immune cells. Those immune cells then make us feel awful. They create inflammation that triggers a scratchy feeling in the throat and leads to the production of a lot of mucus around the site of the infection. In order to recover from a cold, we have to wait not only for the immune system to wipe out the virus but also to calm itself down.

The Egyptian author of the Ebers papyrus wrote that the cure for
resh
was to dab a mixture of honey, herbs, and incense around the nose. In seventeenth-century England, cures included a blend of gunpowder and eggs and of fried cow dung and suet. Leonard Hill, the physiologist who believed a change of temperature caused colds, recommended that children start their day with a cold shower. Today, doctors don’t have much more to offer people who get colds. There is no vaccine. There is no drug that has consistently shown signs of killing the virus. Some studies have suggested that taking zinc can slow the growth of human rhinoviruses, but later studies failed to replicate their results.

In fact, some treatments for the cold may be worse than the disease itself. Parents often give their children cough syrup for colds, despite the fact that studies show it doesn’t make people get better faster. But cough syrup also poses a wide variety of rare yet serious side effects, such as convulsions, rapid heart rate, and even death. In 2008, the Food and Drug Administration warned that children under the age of two—the people who get colds the most—should not take cough syrup.

Another popular treatment for the cold is antibiotics, despite the fact that they only work on bacteria and are useless again viruses. In some cases, doctors prescribe antibiotics because they’re not sure whether a patient has a cold or a bacterial infection. In other cases, they may be responding to pressure from worried parents to do
something
. But unnecessary prescriptions of antibiotics are a danger to us all, because they foster the evolution
of increasingly drug-resistant bacteria in our bodies and in the environment. Failing to treat their patients, doctors are actually raising the risk of other diseases for everyone.

One reason the cold remains incurable may be that we’ve underestimated the rhinovirus. It exists in many forms, and scientists are only starting to get a true reckoning of its genetic diversity. By the end of the twentieth century, scientists had identified dozens of strains, which belonged to two great lineages, known as HRV-A and HRV-B. In 2006, Ian Lipkin and Thomas Briese of Columbia University were searching for the cause of flu-like symptoms in New Yorkers who did not carry the influenza virus. They discovered that a third of them carried a strain of human rhinovirus that was not closely related to either HRV-A or HRV-B. Lipkin and Briese dubbed it HRV-C, and since then, researchers have found that this third lineage is common around the world. From one region to another, the variations in HRV-C’s genes are few, which suggests that the virus wasted no time spreading through our species. In fact, the common ancestor of all HRV-C may be just a few centuries old.

The more strains of rhinoviruses scientists discover, the better they come to understand their evolution. All human rhinoviruses share a core of genes that have changed very little as the viruses have spread around the world. Meanwhile, a few parts of the rhinovirus genome are evolving very quickly. These regions appear to help the virus avoid being killed by our immune systems. When our bodies build antibodies that can stop one strain of human rhinovirus, other strains can still infect us because our antibodies don’t fit on their surface proteins. Consistent with this hypothesis is the fact that people are typically infected by several different human rhinovirus strains each year.

The diversity of human rhinoviruses makes them a very difficult target to hit. A drug or a vaccine that attacks one protein on the surface of one strain may prove to be useless against others that have a version of that protein with a different structure. If another strain of human rhinovirus is even a little resistant to such treatments, natural selection can foster the spread of new mutations, leading to much stronger resistance.