Few things on Earth are spookier than viruses. The very name virus, from the Latin word for "poisonous slime," speaks to our lowly regard for them. Their anatomy is equally dubious: loose, tiny envelopes of molecules—protein-coated DNA or RNA—that inhabit some netherworld between life and nonlife. Viruses do not have cell mb embranes, as bacteria do; they are not even cells. They seem most lifelike only when they invade and co-opt the machinery of living cells in order to make more of themselves, often killing their hosts in the process. Their efficiency at doing so ranks them among the most fearsome killers: Ebola virus, HIV, smallpox, flu. Yet they go untouched by antibiotics, having nothing really biotic about them.

Bernard La Scola peers into an electron microscope
in his laboratory in Marseille, France.

The existence of viruses was first surmised just over a century ago by Dutch botanist Martinus Beijerinck. He mashed up disease-riddled tobacco leaves and then passed the juicy pulp through a porcelain filter fine enough to trap everything down to the tiniest bacteria. When even that filtered fluid infected other plants, a world still acclimating to Louis Pasteur's germ theory now had an even tinier class of pathogens to contemplate. Here were entities so wraithlike that they remained unseen until 1935, when scientists armed with the newly invented electron microscope managed to take a picture of the "poison" lurking in Beijerinck's slime, today known as tobacco mosaic virus.

Less an organism than a jumbled collection of biochemical shards, the virus eventually yielded Wendell M. Stanley, the leader of the research team that exposed it, a Nobel Prize in chemistry rather than biology. The discovery also set off an intense scientific and philosophical debate that still rages: What exactly is a virus? Can it properly be described as alive? " 'Life' and 'living' are words that the scientist has borrowed from the plain man," the British virologist Norman Pirie wrote at the time. "Now, however, systems are being discovered and studied which are neither obviously living nor obviously dead, and it is necessary to define these words or else give up using them and coin others."


Seventy years later, the challenge continues to haunt science. So "other" are viruses that we're still trying to corral them with new metaphors: microzombies, pirates of the cell, submicroscopic hijackers. But even the more restrained characterizations betray a long-standing prejudice. Most biologists typically recognize three official branches of life: the eukaryotes, which are organisms whose cells have a nucleus; bacteria, the single-celled organisms that may or may not possess a nucleus; and archaea, an ancient line of microbes without nuclei that may make up as much as a third of all life on Earth (See "Will the Methane Bubble Burst?" Discover, March 2004). Viruses, being dependent on these organisms to host them, are viewed as evolutionary latecomers: genomic scraps that fell out onto the floor back when life was assembling itself into more complex arrangements.

Bacteriologist Bernard La Scola first identified
Mimivirus, the largest known virus, in 2003.
Although Mimi infects only amoebas, many
of its kin pose a direct threat to humans.

The sheer prevalence of viruses, however, is forcing a reconsideration about how these entities fit into the biological world. Researchers have characterized some 4,000 viruses, from several dozen distinct families. Yet that is a tiny fraction of the number of viruses on Earth. In the last two years, J. Craig Venter, the geneticist who decoded the human genome, has circled the globe in his sailboat and sampled ocean water every couple of hundred miles. Each time he dipped a container overboard, he discovered millions of new viruses—so many that he increased the number of known genes 10-fold. Although we tend to think of viruses only in terms of the damage they do, a broader and more benign picture is emerging. Scientists estimate that they have discovered and documented less than 1 percent of all the living things on the planet. But for every organism in that unidentified 99 percent, at least 10 times as many unknown viruses are thought to exist—the vast majority of which are harmless to life and yet integral to it.

Now, with the recent discovery of a truly monstrous virus, scientists are again casting about for how best to characterize these spectral life-forms. The new virus, officially known as Mimivirus (because it mimics a bacterium), is a creature "so bizarre," as The London Telegraph described it, "and unlike anything else seen by scientists . . . that . . . it could qualify for a new domain in the tree of life." Indeed, Mimivirus is so much more genetically complex than all previously known viruses, not to mention a number of bacteria, that it seems to call for a dramatic redrawing of the tree of life.

"This thing shows that some viruses are organisms that have an ancestor that was much more complex than they are now," says Didier Raoult, one of the leaders of the research team at the Mediterranean University in Marseille, France, that identified the virus. "We have a lot of evidence with Mimivirus that the virus phylum is at least as old as the other branches of life and that viruses were involved very early on in the evolutionary emergence of life."

That represents a radical change in thinking about life's origins: Viruses, long thought to be biology's hitchhikers, turn out to have been biology's formative force.

This is striking news, especially at a moment when the basic facts of origins and evolution seem to have fallen under a shroud. In the discussions of intelligent design, one hears a yearning for an old-fashioned creation story, in which some singular, inchoate entity stepped in to give rise to complex life-forms—humans in particular. Now the viruses appear to present a creation story of their own: a stirring, topsy-turvy, and decidedly unintelligent design wherein life arose more by reckless accident than original intent, through an accumulation of genetic accounting errors committed by hordes of mindless, microscopic replication machines. Our descent from apes is the least of it. With the discovery of Mimi, scientists are close to ascribing to viruses the last role that anyone would have conceived for them: that of life's prime mover.

The green hallways of the second-floor Rickettsia Unit at the Mediterranean University constitute what might be called an archive of agony. Stored there on freezer shelves behind a series of locked lab doors is an array of bacterial pathogens that have been caught and identified by the unit's crack detectives over the years. Rickettsia, the microbe that causes such diseases as typhus and Rocky Mountain spotted fever, resides there alongside many others, from Salmonella to strains of Legionella, a bacterium that causes a severe pneumonia-like disease in humans and was first identified following an outbreak at an American Legion convention in Philadelphia in 1976.

In the early spring of 2003, amid the familiar cast of microbial villains, Bernard La Scola, a bacteriologist at the unit, came upon something that none of his colleagues had ever seen. Focusing his electron microscope on a sample of what he assumed would prove to be an elusive new strain of Legionella, La Scola found himself staring instead at a viral monster.

"I went, 'Whoa,' " he recalls. On his computer he brings up an image, magnified 200,000 times, of the creature: a bug-eyed, hexagonal smurf with a head of electrified hair. That's but one of its looks. In three-dimensional imaging it appears more like a soccer ball. La Scola recognized both shapes as classically viral. Viruses seem to crave such crystal-like geometry, which is one of many reasons they've been thought of as more chemical than biological.

"I'm a bacteriologist," he says. "I don't think in terms of viruses, but this thing was way too big for that. So I called a friend of mine in the faculty of virology, and he came and looked at it and said, 'Oh, yes, it is a virus, but the size . . . ' "

Mimi, the largest known virus.

While there is some evidence to suggest that it may have once caused a type of pneumonia in humans, Mimivirus now seems to infect only amoebas. Until its positive identification in 2003, it was known as Bradfordcoccus and falsely suspected as the cause of a 1992 pneumonia outbreak in the West Yorkshire mill town of Bradford, England. That was where Mimivirus was first found, hiding inside an amoeba at the base of an industrial cooling tower. Cooling towers—along with evaporative condensers, riparian soil, tap water, showerheads, and treated sewage—are all hangouts of Legionella. And amoebas, as Timothy Rowbotham, a former disease detective with Britain's Public Health Laboratory Service, discovered back in 1992, are an ideal tool for collecting Legionella. In the ongoing to and fro between the world's microbes, amoebas are a nearly indomitable foe, gobbling up nearly everything in their path. Legionella, however, turns the tables on amoebas, rendering them both a food source and a perfect lab culture for microbe hunters.