The Viral Storm Read online

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  It’s true that in order to complete their life cycle, viruses have to infect cellular forms of life, but their role is not necessarily destructive or harmful. Like any major component of the global ecosystem, viruses play a vital role in maintaining global equilibrium. The 20 to 40 percent of bacteria in marine ecosystems that viruses kill every day, for example, serves a vital function in the resulting release of organic matter, in the form of amino acids, carbon, and nitrogen. And though studies in this area are few, it is largely believed that viruses, in any given ecosystem, play the role of “trust busters”—helping to ensure that no one bacterial species becomes too dominant—thereby facilitating diversity.

  Given the ubiquity of viruses, it would be surprising indeed if they were relegated to a destructive role. Further studies will likely reveal the profound ecological importance of these organisms not just in destroying but also in benefiting many of the life forms they infect. Since Beijerinck’s discovery, the vast majority of research conducted on viruses has understandably focused on the deadly ones. In the same way, we know much more about venomous snakes, despite the fact that they represent a startlingly small percentage of snake diversity. As we consider the frontiers of virology in part III, we will explore the potential benefits of viruses in detail.

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  Viruses infect all known groups of cellular life. Whether a bacterium living in the high-pressure depths of the planet’s upper crust or a cell in a human liver, for a virus, each is just a place to live and produce offspring. From the perspective of viruses and other microbes, our bodies are habitats. Just as a forest provides a habitat for birds and squirrels, our bodies provide the local environment in which these beings live. And survival in these environments presents a range of challenges. Like all forms of life, viruses compete with each other for access to resources.

  Viruses face constant pressure from our immune systems, which have multiple tactics to block their entrance into the body or disarm and kill them when they manage to get in. They face constant life choices: should they spread, which risks capture by our immune systems, or remain in latency, a form of viral hibernation, which can provide protection but sacrifices offspring.

  The common cold sore, caused by the herpes simplex virus, illustrates some of the challenges that viruses face in negotiating the complex habitats of our bodies. These viruses find refuge in nerve cells, which because of their privileged and protected positions in our bodies do not receive the same level of immune attention as the cells in our skin, mouth, or digestive tract. Yet a herpes virus that maintained itself within a nerve cell without spreading would hit a dead end. So herpes viruses sometimes spread down through the nerve cell ganglions to the face to create virus-loaded cold sores that provide them a route to spread from one person to the next.

  How viruses choose when to launch themselves remains largely unknown, but they almost certainly monitor the environmental variables of their world when making these decisions. Many of the adult humans who are infected with herpes simplex virus know that stress can bring on cold sores. Some also have noted anecdotally that pregnancy seems to bring on active infections. While still speculation, it would not be surprising if viruses responded to environmental cues indicating severe stress or pregnancy by activating. Since severe stress can indicate the possibility of death, it may be their last opportunity to spread—a dead host is also a dead virus. A pregnancy, on the other hand, presents the opportunity for spread either through genital contact with the baby during childbirth or during the kissing that inevitably follows the birth of a baby.

  Transmission from host to host is such a fundamental need for infectious agents that some take it a step further. The incredible malaria parasite Plasmodium vivax hibernans goes so far as to keep a calendar of sorts. Many times larger than herpes simplex virus, parasites like malaria are infectious agents like viruses and bacteria but are in the eukaryotes class, and so are more closely related to animals than they are to the others. Spread by mosquitoes, P. vivax hibernans persists in arctic climates. In these cold locations, it can only infect mosquitoes seasonally during the brief period each summer when the insects hatch. Rather than wasting energy producing offspring all year, the malaria parasite lies dormant for most of the year in the human liver but, during summer, bursts to life, generating its spawn of malaria offspring that spread through an infected person’s blood. While it’s still unclear exactly what triggers the relapse, recent studies suggest that it might be the bites of mosquitoes themselves that provide an indication that the season for spreading has begun.

  The careful timing that viruses and other microbes use when choosing to spread does not differ from the choices that other organisms make. Whether the timing of fruiting in a tropical fruit tree or the timing of mating in water buffalo, living things that time their reproduction appropriately have more successful offspring. This means the traits for accurately timing reproduction will persist and diversify. And how microbes time their growth within our bodies also has a major impact on illness.

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  The majority of microbes that cause infection in humans are relatively harmless, but some have a striking capacity to make us sick. This can sometimes be expressed in the form of, say, a common cold (caused by a rhinovirus or adenovirus) but can also manifest itself in life-threating illnesses such as smallpox.

  Deadly microbes are a consistent challenge to evolutionary biologists because of their paradoxical habit of eviscerating habitats upon which they depend for their own survival. It’s analogous to a bird destroying the forest in which it and its descendants live. Yet the process of evolution occurs largely at the level of the individual or even the gene. Evolution does not proceed with forethought, and there’s nothing to stop a virus from spreading in such a way that leads to a dead end. Such virally induced extinction events have undoubtedly occurred throughout the history of interactions with microbes, no matter the ultimate cost for virus or host.

  More central from the perspective of a virus is the impact of disease on transmission. As we learned in the introduction, on average, each germ must infect at least one new victim for every old one who either dies or recovers and purges himself of the microbe in order to avoid extinction. This is the rule of the basic reproductive number, or R0. If the average number of new victims per old victims drops to less than one, then the spread of the microbe is doomed. Since microbes generally can’t walk or fly from one host to the next they often strategically alter their host to help in their spread. From the perspective of a bug, a symptom can be an all-important means of enlisting our help in moving itself around. Microbes often make us cough or sneeze, which can permit them to spread through our exhaled breath, suffer from diarrhea, which can spread microbes through local water supplies, or cause open sores to appear on our skin, which can spread through skin-to-skin contact. In these cases it’s obvious why a microbe would trigger these generally unpleasant symptoms. Unpleasant symptoms are one thing, but killer microbes are quite another.

  Keeping its host alive and pumping out new microbes would seem to be an ideal plan for a bug. And some bugs do certainly employ such a strategy. Human papillomavirus, or HPV, infects around 50 percent of sexually active adults at some point during their lifetimes. It currently infects around 10 percent of people on the planet, a staggering 650 million people. And while a few strains of HPV cause cervical cancer, most do not. Those strains that do kill their hosts infect them for many years before showing any symptoms at all. Even if the current vaccines that protect against the cancer-causing HPV variants were deployed universally, harmless HPV strains would continue to circulate at huge levels with an impact no greater than occasional if unsightly warts. These viruses can spread effectively without killing. Yet other bugs kill with startling efficiency.

  Bacillus anthracis, a bacterial pathogen of grazing animals like sheep and cattle that occasionally infects humans, causes anthrax infection, which kills quickly and effectively. Following ingestion o
f anthrax spores during grazing, anthrax reactivates and spreads rapidly throughout the animal, often killing it in short order. But this dead host is by no means a dead end. After using the energetic resources of its dying host to replicate in massive numbers, anthrax simply goes back into spore form. Wind, a common feature of the grassy plains of the grazing hosts, then spreads the spores throughout the environment, where they can wait for new prospective victims to arrive. In the case of anthrax, creating hardy spores frees the bug from any negative consequences of its destruction.

  Such situations are not limited to spore-forming bacteria. The cholera bacterium, which gives us diarrhea, and the smallpox virus, which causes severe viral disease, both kill in only days or weeks. But before the deaths take place, the deadly symptoms spread trillions of microbes to potential new victims. Human deaths, while unfortunate to us, represent a mere consequence of the conditions the bugs need to get to their next hosts.

  From the perspective of a bug the impact on its host is only measured in its ability to survive and reproduce. And altering our physical bodies is just the beginning. Some microbes also influence our behavior, effectively making us zombies acting in their benefit. One of the most striking examples comes from a feline parasite, Toxoplasma gondii. While toxo, as parasitologists refer to it, can infect a range of mammals from humans to rodents, its life cycle cannot be completed until it lands in a cat. This parasite has found a frighteningly effective way to get home when it ends up in the wrong mammal. Careful studies have documented how the parasite spreads to the nervous system of infected, unsuspecting rodents and hijacks their brains. Sometime after infection, having spent much of their life steering clear of cats, mice begin to see them as positively enticing. This fatal attraction leads to a dead mouse, but also a toxo cyst that has the potential to complete its life cycle in the newly infected, not to mention, satiated, cat.

  Truly deadly diseases must strike a balance between the likelihood of causing death in its victim once the victim is infected and their efficacy in terms of allowing the victim to spread the disease to others. You can’t generally have your cake and eat it, too—producing many microbes in a host increases the chance that they’ll spread but also harms the host. Consequently, microbes sometimes use very different methods to cause devastation. They can keep the carrier alive for a long time, which carries the potential to infect multiple victims over many months or years, as in the case of the HPV virus. Or they can kill and spread quickly, infecting dozens of new victims in the course of a day, as in the case of smallpox and cholera.

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  That a tiny microbe has the potential to alter the body and behavior of its host represents an enormous logistical feat. As scientists sequence the genomes of different species, they provide information on the relative size of the genetic blueprints that permit these organisms to function and give us a sense of how enormous the feat is. The numerical genome sizes of many cellular forms of life can range into the billions—humans, for example, have around three billion base pairs (i.e., bits of genetic information); corn has around two billion. Certain viruses like HIV and the Ebola virus, which use RNA rather than DNA for their genetic information, manage to live with an average of only ten thousand base pairs of genetic information, an incredible level of biological minimalism. How they manage to replicate with such a small amount of genetic information, let alone do something remarkably complicated, like altering the behavior of their hosts, is truly amazing.

  Viruses manage to function with such few genes through a variety of tricks that allow them to maximize the impact of their diminutive genomes. Among the most elegant is a phenomenon called overlapping reading frames. As an analogy, take a poem of around thirteen thousand letters—say, T. S. Eliot’s poem The Waste Land. It has roughly the same number of letters as the Ebola virus has base pairs. When you read The Waste Land, it has meaning, tempo, reference—all of the characteristics we normally expect from literature. In the same way, the genome of the Ebola virus has meaning, with base pair letters making up genes that get translated into the proteins that provide the virus with its capacity to function. If you take the first stanza of The Waste Land, around a thousand letters, and begin to read it starting with the second letter instead and move the first letters of the other words, it’s a disaster. “April is the cruelest month” becomes “Prili sthec rueles tmonth.” Nonsense.

  Now imagine that embedded within the stanza was a second poem so that both readings, the one that starts with the first letter and the one that starts with the second letter, lead to fluent comprehensible verses. Now imagine that you took the same stanza and read it backward and that a third hidden stanza emerged from the same letters. This is precisely what viruses can do. A good challenge to poets (or perhaps computer scientists) would be to create such a stanza to see if they could be as creative as natural selection has been with viruses. Viruses with overlapping reading frames use the same string of base pairs to code up to three different proteins, an incredible genomic efficiency, which makes their small genomes pack a much larger punch.

  Overlapping reading frames represent just one of a range of adaptations that viruses have to negotiate their worlds. Perhaps even more important for viruses is their capacity to generate genetic novelty. Viruses have a diverse toolbox for altering themselves. Among the most fundamental is simple mutation. No organisms have perfect fidelity. Any time a cell in our body or a bacterium divides to create daughter cells or a virus replicates in a host cell, errors creep in. This means that even in the absence of sexual mixing, offspring are never the same as their parents. Yet viruses have taken mutation to a completely new level.

  Viruses have some of the highest mutation rates of any known organisms. Some groups of viruses, such as RNA viruses, have such high error rates that they approach a threshold where any higher level of mutation would make them effectively crash due to the loss of essential function from the resulting errors. While many of the mutations harm the new viruses, the high number of offspring that viruses produce increases the chances that some mutants survive and occasionally outperform their parents. This raises the chances that they will successfully evade the immune systems of their host, get the upper hand against a new drug, or gain the capacity to jump to a completely new host species.

  Middle-school biology teaches us that life is made up of sexual or asexual organisms. Yet viruses and other microbes exchange genetic information in ways that should make us question our early textbooks. When two different varieties of virus infect the same host, from time to time they infect the same cell, setting the stage for such exchange. In these cases, viruses sometimes create mosaic daughter viruses, which include some genetic parts from one of the viruses and completely different elements from another. In the case of reassortment, entire gene segments are swapped between certain kinds of viruses. In recombination, genetic material from one virus is swapped into a second virus. Genetic mixing of both sorts provides viruses with a rapid and radical way to create novelty. As with mutation, the novel daughter viruses have new blueprints that occasionally help them survive and spread.

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  Our knowledge of microbes is still young. This vast unseen world is critical to our planet and our species, yet we understand very little about it. We’ve already discovered most of the plant and animal life on our planet, but we regularly discover brand-new microbes. Ongoing studies of the diversity of microbes in animals, plants, soils, and aquatic systems represent the tip of a very large iceberg. The millions of specimens that will result from these studies will catalyze our understanding of life. Among other things, the knowledge will help spark the development of new antibiotics. It will also help us forecast the next pandemic. The microbial world is the “new world,” the last frontier of undiscovered life on our planet.

  2

  THE HUNTING APE

  I wiped the sweat out of my eyes and swatted away the prickly branches in my path as I tried to listen for the screeches and hollers of the wild chimpanze
es my colleagues and I had been trailing through Uganda’s Kibale Forest for the past five hours. The sudden silence of the three large male chimpanzees could only mean trouble. At times, such silence can foreshadow a sudden murderous rush into a neighboring territory to kill competing males. Or perhaps scientists. Chimpanzee warfare was not, thankfully, in the air that day. When our group emerged into a small clearing, we observed the chimpanzees seeming to quietly confer with one another as a crew of red colobus monkeys ate and played in the fig trees above, unaware of any danger. As two of the males inched up two nearby trees, the third—the apparent leader—created a diversion by screaming and scrambling up the tree toward the monkeys. Commotion ensued as the monkeys scrambled out of the tree and landed in the path of the other two hunters, waiting. One of the chimpanzees grabbed a young monkey and made his way to the ground to share his catch with his teammates.

  As the chimpanzees feasted on the monkey’s raw flesh, a rush of thoughts ran through my brain: teamwork, strategy, flexibility. All in this close relative to humans. Truly, this was why people studied chimpanzees. While the rigors of scientific literature would never allow us to state this in technical journal articles, the reality seemed clear enough—these chimpanzees had worked collectively and strategically to mount a coordinated attack. The leader had diminished his chances of landing a kill by making a noisy attack, but the knowledge that his actions would increase the chances of success for his partners made this a strategic approach. In the end, they’d share the meat no matter who made the kill, exactly the sort of behavior that humans display every day. As the chimpanzees tore through the animal, it also occurred to me that the contact with the monkey’s blood and guts provided the ideal opportunity for our carnivorous kin to contract microbes.