A Planet of Viruses - Carl Zimmer (2011)



The Uncommon Cold


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.

Despite the diversity of rhinoviruses, some scientists are optimistic that they can develop a cure for the common cold. The fact that all strains of human rhinoviruses share a common core of genes suggests that the core can’t withstand mutations. In other words, viruses with mutations in the core die. If scientists can figure out ways to attack the rhinovirus core, they may be able to stop the disease. One promising target is a stretch of genetic material in rhinoviruses that folds into a loop shaped like a clover leaf. Every rhinovirus scientists have studied carries the same clover-leaf structure, which appears to be essential for speeding up the rate at which a host cell copies rhinovirus genes. If scientists can find a way to disable the clover leaf, they may be able to stop every cold virus on Earth.

But should they? Human rhinoviruses certainly impose a burden on public health, not just by causing colds but by opening the way for more harmful pathogens. But the human rhinovirus itself is relatively mild. Most colds are over in a week, and 40 percent of people who test positive for rhinoviruses suffer no symptoms at all. In fact, human rhinoviruses may offer some benefits to their human hosts. Scientists have gathered a great deal of evidence that children who get sick with relatively harmless viruses and bacteria may be protected from immune disorders when they get older, such as allergies and Crohn disease. Human rhinoviruses may help train our immune systems not to overreact to minor triggers, instead directing their assaults to real threats. Perhaps we should not think of colds as ancient enemies but as wise old tutors.