A Planet of Viruses

by Carl Zimmer

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.

The genes of a flu virus are stored on eight separate segments, and when a host cell starts manufacturing the segments from two different viruses at once, they sometimes get mixed together. The new offspring end up carrying genetic material from both viruses. This mixing, known as reassortment, is a viral version of sex.

It turns out that papillomaviruses infect not just mammals, such as humans, rabbits, and cows, but other vertebrates as well, such as birds and reptiles. Each strain of virus typically only infects one or a few related species. Based on their relationships, Marc Gottschling of the University of Munich has argued that the first egg-laying land vertebrates— the ancestor of mammals, reptiles, and birds—was already a host to papillomaviruses three hundred million years ago.

Viruses outnumber all other residents of the ocean by about fifteen to one. If you put all the viruses of the oceans on a scale, they would equal the weight of seventy-five million blue whales. And if you lined up all the viruses in the ocean end to end, they would stretch out past the nearest sixty galaxies.

When Felix d’Herelle discovered the first bacteriophage in French soldiers in 1917, many scientists refused to believe that such a thing actually existed. A century later, it’s clear that Herelle had found the most abundant life form on Earth. Ever since Proctor’s discovery of the abundance of marine viruses, scientists have been documenting their massive influence on the planet. Marine phages influence the ecology of the world’s oceans. They leave their mark on Earth’s global climate. And they have been playing a crucial part in the evolution of life for billions of years. They are, in other words, biology’s living matrix.

Marine viruses are powerful because they are so infectious. They invade a new microbe host ten trillion times a second, and every day they kill about half of all bacteria in the world’s oceans.

In a survey of viruses in the Arctic Ocean, the Gulf of Mexico, Bermuda, and the northern Pacific, scientists identified 1.8 million viral genes. Only 10 percent of them showed any match to any gene from any microbe, animal, plant, or other organism—even from any other known virus. The other 90 percent were entirely new to science. In 200 liters of seawater, scientists typically find 5,000 genetically distinct kinds of viruses.

Temperate phages merge seamlessly into their host’s DNA; when the host reproduces, it copies the virus’s DNA along with its own. As long as a temperate phage’s DNA remains intact, it can still break free from its host during times of stress. But over enough generations, a temperate phage will pick up mutations that hobble it, so that it can no longer escape. It becomes a permanent part of its host’s genome.

Endogenous retroviruses can linger in their hosts for millions of years. In 2009, Aris Katzourakis, an evolutionary biologist at the University of Oxford, discovered hundreds of copies of endogenous retroviruses in the genome of the three-toed sloth. Their genes closely matched those of foamy viruses, free-living pathogens that infect primates and other mammals. Katzourakis concluded that foamy viruses infected the common ancestor of three-toed sloths and primates, which lived a hundred million years ago. In primates, they’ve remained free-living. In the sloth lineage, however, they became trapped in their host’s DNA and have remained there ever since.

Over millions of years, our genomes have picked up a vast amount of DNA from dead viruses. Each of us carries almost a hundred thousand fragments of endogenous retrovirus DNA in our genome, making up about 8 percent of our DNA. To put that figure in perspective, consider that the twenty thousand protein-coding genes in the human genome make up only 1.2 percent of our DNA. Scientists have also observed millions of smaller pieces of “jumping DNA” in the human genome. It’s possible that many of those pieces evolved from endogenous retrovirus, having been stripped down to the bare essentials required for copying DNA.

When a fertilized egg develops into a fetus, for example, some of its cells develop into the placenta, an organ that draws in nutrients from the mother’s tissues. The cells in the outer layer of the placenta fuse together, sharing their DNA and other molecules. Heidmann and other researchers have found that a human endogenous retrovirus gene plays a crucial role in that fusion. The cells in the outer placenta use the gene to produce a protein on their surface, which latches them to neighboring cells. In our most intimate moment, as new human life emerges from old, viruses are essential to our survival. There is no us and them—just a gradually blending and shifting mix of DNA.

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.

Over the past three thousand years, smallpox may have killed more people than any other disease on Earth.

Some thirty-five hundred years ago, smallpox left its first recorded trace on humanity: three mummies from ancient Egypt,

Between 1400 and 1800, smallpox killed an estimated five hundred million people every century in Europe alone.

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.

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.

In 1992, a microbiologist named Timothy Rowbotham scooped up some water from a hospital cooling tower in the English city of Bradford. He put it under a microscope and saw a welter of life. He saw amoebae and other single-celled protozoans, about the size of human cells. He saw bacteria, about a hundred times smaller. Rowbotham was searching for the cause of an outbreak of pneumonia that had been raging through Bradford. In the ranks of the microbes he found in the cooling tower water, he thought he found a promising candidate: a sphere of bacterial size, sitting inside an amoeba. Rowbotham believed he had found a new bacterium, and dubbed it Bradfordcoccus.

Scientists have long seen a huge gulf dividing viruses from “true” living things—bacteria, protozoans, plants, animals, and fungi. Many pointed to the tiny number of genes in viruses, arguing that there was no way for them to gain more because of their peculiar way of reproducing. Because viruses hijack cells to make new viruses, they are sloppy about copying their genes. They don’t carry their own repair enzymes that can fix errors, for example. As a result, they are much more vulnerable to lethal mutations. If a virus accumulated thousands of genes, its high mutation rate would wipe it out.

Forced to carry tiny genomes, viruses could not make room for genes that did anything beyond make new viruses and help those viruses escape destruction. They could carry genes to let them eat, for example. They could not turn raw ingredients into new genes and proteins on their own. They could not grow. They could not expel waste. They could not defend against hot and cold. They could not reproduce by splitting in two. All those nots added up to one great, devastating Not. Viruses were not alive.

Mimiviruses, for example, went overlooked for so long in part because they were a hundred times bigger than viruses are supposed to be. They are also loaded with far too many genes to fit old-fashioned notions of a virus. Scientists don’t know what mimiviruses do with all of their genes, but some suspect that they do some rather lifelike things with them.

Drawing a bright line between life and nonlife can also make it harder to understand how life began in the first place. Scientists are still trying to work out the origin of life, but one thing is clear: it did not start suddenly with the flick of a great cosmic power switch. It’s likely that life emerged gradually, as raw ingredients like sugar and phosphate combined in increasingly complex reactions on the early Earth. It’s possible, for example, that single-stranded molecules of RNA gradually grew and acquired the ability to make copies of themselves. Trying to find a moment in time when such RNA-life abruptly became “alive” just distracts us from the gradual transition to life as we know it.

When they try to trace the common ancestry of virus genes, they often work their way back to a time before the common ancestor of all cell-based life. Viruses may have first evolved before the first true cells even existed. At the time, life may have consisted of little more than brief coalitions of genes, which sometimes thrived and sometimes were undermined by genes that acted like parasites.