A Planet of Viruses - Carl Zimmer (2011)

Epilogue

The Alien in the Watercooler

Mimivirus

Wherever there is water on Earth, there is life. The water may be a pond in a tropical forest, a pool in the Cave of Crystals, or a cooling tower sitting on the roof of a hospital.

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.

Rowbotham spent years trying to make sense of Bradfordcoccus, to see if it was the culprit in the pneumonia outbreak. He tried to isolate its genes by searching for stretches of DNA found in all bacteria, but he couldn’t find any. Budget cuts forced Rowbotham to close his lab down in 1998, and so he arranged for French colleagues to store his samples. For five years, Bradfordcoccus languished in obscurity, until Bernard La Scola of Mediterranean University, decided to take another look at it. As soon as he put Rowbotham’s samples under a microscope, he realized something was not right.

Bradfordcoccus did not have the smooth surface of spherical bacteria. Instead, it was more like a soccer ball, made up of many interlocking plates. And radiating out from its geometric shell La Scola saw hairlike threads of protein. The only things in nature that have these kinds of shells and threads were viruses. But La Scola knew, like all microbiologists at the time knew, that something the size of Bradfordcoccus was a hundred times too big to be a virus.

Yet a virus is exactly what Bradfordcoccus turned out to be. La Scola and his colleagues discovered that it reproduced by invading amoebae and forcing them to build new copies of itself. Only viruses reproduce this way. La Scola and his colleagues gave Bradfordcoccus a new name to reflect its viral nature. They called it a mimivirus, in honor of the virus’s ability to mimic bacteria.

The French scientists then set out to analyze the genes of the mimivirus. Rowbotham had tried—and failed—to match its genes to those of bacteria. The French scientists had better luck. The mimivirus had virus genes—and a lot of them. Before the discovery of mimiviruses, scientists were used to finding only a few genes in a virus. But mimiviruses have 1,262 genes. It was as if someone took the genomes of the flu, the cold, smallpox, and a hundred other viruses and stuffed them all into one protein shell. The mimivirus even had more genes than some species of bacteria. In both its size and its genes, mimivirus had broken cardinal rules for being a virus.

Once La Scola and his colleagues knew what mimivirus genes looked like, they began to search for them in other habitats. They found the giant viruses in the lungs of hospital patients suffering from pneumonia. It’s not clear yet if mimiviruses actually cause pneumonia, as Rowbotham had originally suspected, or if they just colonize people who are already sick. Scientists have also found mimiviruses and related giant viruses far from hospitals. They are actually common in the world’s oceans, where they infect algae and perhaps even corals and sponges. Until now, scientists have realized, these giant viruses have been hiding in plain sight.

Newly discovered viruses like the mimivirus are forcing scientists to rethink what it means to be a virus in the first place. Their old rules, once so ironclad, are buckling. And as scientists debate what it means to be a virus, they are debating an even bigger question: what it means to be alive.

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.

The sizes of virus genomes offered some good reason to believe this was actually true. Viruses carry genes encoded either in DNA, or its single-stranded version, RNA. For a number of reasons, RNA is an inherently more error-prone molecule to copy. And it turns out that RNA viruses, like influenza and HIV, have smaller genomes than DNA viruses.

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.

To be alive, many scientists argued, required having a true cell. “An organism is constituted of cells,” the microbiologist Andre Lwoff declared in a lecture he gave when he accepted the Nobel Prize in 1967. Lacking cells, viruses were considered as little more than cast-off genetic material that happened to have the right chemistry to get replicated inside cells that were truly alive. Scientists could purify viruses down to crystals, the same way they could crystallize salt or pure DNA. No one could ever crystallize a maple tree. In 2000, the International Committee on Taxonomy of Viruses declared that “viruses are not living organisms.”

In the decade following that declaration, a number of scientists rejected it outright. The old rules no longer work well in the face of new viruses. 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. Some of their proteins, for instance, look a lot like the proteins our own cells use to assemble new genes and proteins. When mimiviruses invade amoebae, they don’t dissolve into a cloud of molecules. Instead, they set up a massive, intricate structure called a viral factory. The virus factory takes in raw ingredients through one portal, and then spits out new DNA and proteins through two others. The viral factory looks and acts remarkably like a cell. It’s so much like a cell, in fact, that La Scola and his colleagues discovered in 2008 that it can be infected by a virus of its own. It was the first time anyone had found a virus of a virus. It was yet another thing that ought not to exist.

Drawing dividing lines through nature can be scientifically useful, but when it comes to understanding life itself, those lines can end up being artificial barriers. Rather than trying to figure out how viruses are not like other living things, it may be more useful to think about how viruses and other organisms form a continuum. We humans are an inextricable blend of mammal and virus. Remove our virus-derived genes, and we would be unable to reproduce. We would probably also quickly fall victim to infections from other viruses. Some of the oxygen we breathe is produced through a mingling of viruses and bacteria in the oceans. That mixture is not a fixed combination, but an ever-changing flux. The oceans are a living matrix of genes, shuttling among hosts and viruses.

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.

Banning viruses from the Life Club also deprives us of some of the most important clues to how life began. One of the great discoveries about viruses has been the tremendous diversity in their genes. Every time scientists find new viruses, most of their genes bear little resemblance to any gene ever found before. The genes of viruses are not a meager collection of DNA cast off in recent years from true living things. Many scientists now argue that viruses contain a genetic archive that’s been circulating the planet for billions of years. 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. Patrick Forterre, a French virologist, has even proposed that in the RNA world, viruses invented the double-stranded DNA molecule as a way to protect their genes from attack. Eventually their hosts took over their DNA, which then took over the world. Life as we know it, in other words, may have needed viruses to get its start.

At long last, we may be returning to the original two-sided sense of the word virus, which originally signified either a life-giving substance or a deadly venom. Viruses are indeed exquisitely deadly, but they have provided the world with some of its most important innovations. Creation and destruction join together once more.