A Planet of Viruses (11 page)

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Authors: Carl Zimmer

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Once vaccines became common, smallpox began to lose its fierce grip on humanity. Through the early 1900s, one country after another recorded their last case of smallpox. By 1959, smallpox had retreated from Europe, the Soviet Union, and North America. It remained a scourge of tropical countries with poor medical systems in place. But it was beaten so far back that some public
health workers began to contemplate an audacious goal: eliminating smallpox from the planet altogether.

 

The advocates of smallpox eradication built their case on the biology of the virus. Smallpox only infects humans, not animals. If it could be systematically eliminated from every human population, there would be no need to worry that it was lurking in pigs or ducks, waiting to reinfect us. What’s more, smallpox is an obvious disease. Unlike a virus like HIV, which can take years to make itself known, smallpox declares its gruesome presence in a matter of days. Public health workers would be able to identify outbreaks and track them with great precision.

 

Yet the idea of eradicating smallpox met with intense skepticism. If everything went exactly according to plan, an eradication project would require years of labor by thousands of trained workers, spread across much of the world, toiling in many remote, dangerous place. Public health workers had already tried to eradicate other diseases, like malaria, and failed.

 

The skeptics lost the debate, however, and in 1965, the World Health Organization launched the Intensified Smallpox Eradication Programme. The eradication effort was different in many ways from previous campaigns. It relied on a new prong-shaped needle that could deliver smallpox vaccine far more efficiently than regular syringes. As a result, vaccine supplies could be stretched much further than before. Public health workers also designed smart new strategies for administering vaccines. Trying to vaccinate entire countries was beyond the reach of the eradication project. Instead, public health workers identified outbreaks and took quick action to snuff them out. They quarantined victims and then vaccinated people in the surrounding villages and towns. The smallpox would spread like a forest fire, but soon it would hit the firebreak of vaccination and die out.

 

Outbreak by outbreak, the virus was beaten back, until the last case was recorded in Ethiopia in 1977. The world was now free of smallpox.

 

While the eradication campaign was a huge success, the smallpox virus had not disappeared completely. Scientists had established stocks of the virus in their laboratories to study. The WHO
had all the stocks gathered up and deposited in two approved laboratories, one in the Siberian city of Novosibirsk in the Soviet Union, and one at the U.S. Centers for Disease Control and Prevention in Atlanta, Georgia. Smallpox experts could still study stocks from the two labs, but only under tight regulations. Most experts assumed that before long those last two collections of smallpox would be destroyed as well, and then the virus would become truly extinct.

 

It turns out, however, that there might actually be more smallpox virus in the world. In the 1990s, Soviet defectors revealed that their government had actually set up labs to produce a weaponized smallpox virus that could be loaded onto missiles and launched at enemy targets. After the fall of the Soviet government, the labs were abandoned. No one knows what ultimately happened to all the stocks of smallpox virus. We are left with the terrifying possibility that ex-Soviet virologists sold smallpox stocks to other governments or even terrorist organizations.

 

When these revelations emerged, some scientists and government officials decided the research stocks had to be preserved. Scientists could study them to help prepare for biological warfare. There remains much scientists don’t yet understand about smallpox. In recent years, scientists have started to decipher the strategies smallpox uses to fight the immune system. They have discovered an arsenal of weapons the virus deploys. Smallpox proteins can jam the signals the immune cells pass to each other to mobilize an attack, for example. Scientists have yet to figure out why smallpox is so deadly. Some researchers argue that the virus causes the immune system to attack a victim’s own body, rather than the virus. But that’s just a hypothesis still to be tested. Solving mysteries like these could conceivably lead to better vaccines, and even to antiviral drugs that might be effective against smallpox infections or other dangerous viruses that are equally deadly to humans.

 

In 2010, the WHO reopened the debate over whether to finally destroy the two remaining officially declared stocks smallpox in Russia and the United States. But now the debate has taken a twist that previous generations of smallpox fighters could never
have dreamed of. Today scientists know the full genetic sequence of the smallpox virus. And they have the technology necessary to synthesize the smallpox genome from scratch. Synthesizing viruses is not the stuff of science fiction; scientists have already manufactured the genetic material of other viruses, like polio and the deadly 1918 influenza, and have used it to generate full-blown viruses.

 

There’s no evidence that anyone has tried to resurrect smallpox in the same way, but, then again, there’s no evidence that it would be impossible to do so. After thirty-five hundred years of suffering and puzzling over smallpox, we have finally figured it out. And yet, by understanding smallpox, we have ensured that it can never be utterly eradicated as a threat to humans. Our knowledge gives the virus its own kind of immortality.

 

 
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.

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