“And why is that important?” I asked.
“Because we’re looking for the Next Big One,” she said.
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The Next Big One, as I mentioned at the start of this book, is a subject that disease scientists around the world often address. They think about it, they talk about it, and they’re quite accustomed to being asked about it. As they do their work or discuss pandemics of the past, the Next Big One (NBO) is at the back of their minds.
The most recent big one is AIDS, of which the eventual total bigness (the scope of its harm, the breadth of its reach) cannot even be predicted. About 30 million deaths, 34 million living people now infected, with no end in sight. Polio was a big one, at least in America, where it achieved special notoriety by crippling a man who would become president despite it. Polio also, during its worst years, struck hundreds of thousands of children and paralyzed or killed many, captured public attention like headlights freezing a deer, and brought drastic changes to the way large-scale medical research is financed and conducted. The biggest of the big ones during the twentieth century was the 1918–1919 influenza. Before that, on the North American continent, the big one for native peoples was smallpox, arriving from Spain about 1520 with the expedition that helped Cortez conquer Mexico. Back in Europe, two centuries earlier, it was the Black Death, probably attributable to bubonic plague. Whether the plague bacterium or another, more mysterious pathogen caused the Black Death (as several historians have recently argued), there’s no question of its bigness. Between the years 1347 and 1352, this epidemic seems to have killed at least 30 percent of the people in Europe.
Moral: If you’re a thriving population, living at high density but exposed to new bugs, it’s just a matter of time until the NBO arrives.
Note that most of these big ones but not all of them (plague the exception) were viral. Now that modern antibiotics are widely available, vastly reducing the lethal menace of bacteria, we can guess confidently that the Next Big One will be a virus too.
To understand why some outbreaks of viral disease go big, others go really big, and still others sputter intermittently or pass away without causing devastation, consider two aspects of a virus in action: transmissibility and virulence. These are crucial parameters, defining and fateful, like speed and mass. Along with a few other factors, they largely determine the gross impact of any outbreak. Neither of the two is an absolute constant; they vary, they’re relative. They reflect the connectedness of a virus to its host and its wider world. They measure situations, not just microbes. Transmissibility and virulence: the yin and yang of viral ecology.
You’ve heard a bit already about transmissibility, including the simple statement that viral survival demands replication and transmission. Replication can occur only within cells of a host, for the reasons I’ve mentioned. Transmission is travel from one host to another, and transmissibility is the packet of attributes for achieving it. Can the virions concentrate themselves in a host’s throat or nasal passages, cause irritation there, and come blasting out on the force of a cough or a sneeze? Once launched into the environment, can they resist desiccation and ultraviolet light for at least a few minutes? Can they invade a new individual by settling onto other mucous membranes—in the nostrils, in the throat, in the eyes—and gaining attachment, cell entry, another round of replication? If so, that virus is highly transmissible. It goes airborne from one host to another.
Fortunately, not every virus can do that. If HIV-1 could, you and I might already be dead. If the rabies virus could, it would be the most horrific pathogen on the planet. The influenzas are well adapted for airborne transmission, which is why a new strain can circle the world within days. The SARS virus travels this route too, or anyway by the respiratory droplets of sneezes and coughs—hanging in the air of a hotel corridor, moving through the cabin of an airplane—and that capacity, combined with its case fatality rate of almost 10 percent, is what made it so scary in 2003 to the people who understood it best. But other viruses employ other means of transmission, each with its own advantages and limitations.
The oral-fecal route sounds disgusting but is really quite common. It works well for some viruses because host creatures (including humans) are often forced, especially when living at high densities, to consume food or water contaminated by excrement from other members of their population. This is one of the reasons why children die of dehydration in rainy refugee camps. The virus goes in the mouth, replicates in the belly or the intestines, causes gastrointestinal distress, may or may not spread to other parts of the body, and comes gushing out the anus. Diarrhea, for such a virus, is part of an effective strategy for dispersal. Viruses transmitted this way tend to be fairly hardy in the environment, because they may need to linger in that polluted sump for a day or two before some desperate person comes to drink from it. There’s an entire group of such viruses, known as the enteroviruses, including polio and about seventy others, that attack us in the gut. Most of those enteroviruses are uniquely human infections, not zoonoses. Evidently they don’t need other animal hosts for maintaining themselves in a crowded human world.
For blood-borne viruses, transmission is more complicated. Generally it depends on a third party, a vector. The virus must replicate abundantly in the blood of the host to produce severe viremia (that is, a flood of virions). The vector (a blood-sucking insect or some other arthropod) must arrive for a meal, bite the host, slurp up virions along with the blood, and carry them away. The vector itself must be a hospitable host, so that the virus replicates further within it, producing many more virions that make their way back to the mouth area and stand ready for release. Then the vector must drool virions (as anticoagulant saliva) into the next host it bites. The yellow fever virus, West Nile, and dengue transmit this way. It has an upside and a down.
The downside is that vector transmission requires adaptations for two very different sorts of environment: the bloodstream of a vertebrate and the belly of an arthropod. What works well in one may not work at all in the other, so the virus must carry genetic preparedness for both. The upside is that a vector-borne virus has a vehicle that can carry it some distance, searching thirstily for new hosts. A sneeze travels downwind, more or less at random, but a mosquito can fly upwind toward a victim. That’s what makes vectors such effective modes of transmission.
Blood-borne viruses can also spread to new hosts by way of hypodermic needles and transfusions. But those opportunities are adventitious addenda, recent and accidental, patched onto ancient viral strategies shaped by evolution. Ebola and HIV-1, two viruses of very different character, very different adaptive strategies, both happen to move well via needles. So does hepatitis C virus.
In the case of Ebola, transmission from human to human occurs also by blood-to-blood contact in intimate situations, as when one person takes care of another. For a nursing sister in a Congolese clinic with small cracks on her chapped hands, a few minutes spent wiping bloody diarrhea off the floor could be exposure enough. This is extraordinary transmission, so far as the virus is concerned. Ordinary transmission is however Ebola gets from one individual to another within whatever animal host—identity still unknown—serves as its reservoir. Ordinary transmission allows the virus to perpetuate itself. Extraordinary transmission gives it a burst of high replication, high notoriety, but soon brings it to a dead end. Passing between people via bloody rags or reused needles, in this or that African clinic, is not a strategy that serves Ebola for long-term survival. It’s just an occasional anomaly that has little or no significance (so far, anyway) within Ebola’s broader evolutionary history. Of course, that could change.
Ordinary transmission, for Ebola, need not be blood-borne. If the virus resides in fruit bats of the Central African forest, as suspected but not yet proven, then it might pass from bat to bat during sex, or suckling of infants, or mutual grooming among adults, or breathing on one another, or biting and scratching, or any other form of close contact. At this point in Ebola research, we can on
ly guess. Drops of urine, falling from one bat into the eyes of another? Saliva on shared fruit? Blood-sucking bat bugs? Saliva on fruit would explain how Ebola gets into chimpanzees and gorillas. Bat bugs (yes, there are such things, related to bedbugs) would allow us to imagine a specialist parasite I’ll call Cimex ebolaensis. It’s all speculation. We might even come to learn that Ebola is a natural infection of African ticks, who carry it among fruit bats, gorillas, and chimps. Merely a thought. But please remember that I’ve just invented tick-borne Ebola from zero evidence.
Sexual transmission is a good scheme for viruses with low hardiness in the external environment. It’s a mode of passage that doesn’t require them to go outside. They’re virtually never exposed to daylight or dry air. The virions pass from one body to another by way of direct, intimate contact between host cells lining delicate genital and mucosal surfaces. Rubbing (not just pressing) those surfaces together probably helps. Transmission during coitus is a conservative strategy, reducing risk to such viruses, sparing the need for hardening against desiccation or sunlight. But it has a downside too—notably, that opportunities for transmission are fewer. Even the most lubricious humans don’t have sex as often as they exhale. So the sexually transmitted viruses tend toward patience. They cause persistent infections and endure long periods of latency, punctuated by recurrent outbreaks (like herpesviruses); or else they replicate slowly (like HIV-1 and hepatitis B) up to a critical point at which things get bad. Such patience within a host gives the virus more time and therefore more sexual encounters by which to get itself passed along.
Vertical transmission, meaning mother-to-offspring, is another slow, cautious mode. It can occur during pregnancy, during birth, or (in the case of mammals) by way of milk while an infant nurses. HIV-1, for instance, can be transmitted from mother to fetus across the placenta, or to a newborn in the birth canal, or through breastfeeding; but each of those outcomes is far from inevitable, and the likelihood of their occurrence can be lowered with medical precautions. Rubella (loosely known as German measles) is caused by a virus capable of vertical as well as airborne transmission, and it can kill a fetus or inflict severe damage, including heart disorders, blindness, and deafness. That’s why young girls were counseled, in the era before rubella vaccine, to get themselves infected with the virus—suffer a mild bout and be done with it, permanently immune—before they reached childbearing age. From a strictly evolutionary perspective, though, vertical transmission is not a strategy upon which rubella virus could depend for long-term success. A miscarried fetus or a blinded baby with heart troubles will most likely be a dead-end host, just as terminal for the virus as a Congolese nun with Ebola.
Whatever mode of transmission a virus favors—airborne, oral-fecal, blood-borne, sexual, vertical, or just getting itself passed along in the saliva of a biting mammal, like rabies—the common truth is that this factor doesn’t exist independently. It functions as half of that ecological yin-yang.
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And the other half, virulence, is more complicated. In fact, virulence is such an iridescent, relativistic concept that some experts refuse to use the word. They prefer “pathogenicity,” which is nearly a synonym but not quite. Pathogenicity is the capacity of a microbe to cause disease. Virulence is the measurable degree of such disease, especially as gauged against other strains of similar pathogen. To say that a virus is virulent almost sounds tautological—the noun and the adjective come from a single Latin root, after all. But if “virus” hearkens back to “poisonous slime,” the point of virulence is to ask, How poisonous? The virulence of a given virus within a given host tells you something about the evolutionary history between the two.
Just what does it tell you? That’s the tricky part. Most of us have heard an old chestnut on the subject of virulence: The first rule of a successful parasite is Don’t kill your host. One medical historian has traced this idea back to Louis Pasteur, noting that the most “efficient” parasite, in Pasteur’s view, was one that “lives in harmony with its host,” and therefore latent infections should be considered “the ideal form of parasitism.” Hans Zinsser voiced the same notion in Rats, Lice and History, observing that a long period of association between one species of parasite and one species of host tends to lead, by evolutionary adaptation, to “a more perfect mutual tolerance between invader and invaded.” Macfarlane Burnet agreed:
In general terms, where two organisms have developed a host-parasite relationship, the survival of the parasite species is best served, not by destruction of the host, but by the development of a balanced condition in which sufficient of the substance of the host is consumed to allow the parasite’s growth and multiplication, but not sufficient to kill the host.
It does seem logical, at first consideration, and it’s still often taken as dogma—at least by people who don’t happen to study the evolution of parasites. But even Zinsser and Burnet, to their credit, hedged their endorsements of this idea. They must have recognized that the “rule” was just a generalization with important, revealing exceptions. Some very successful viruses do kill their hosts. Lethalities of 99 percent, and persisting at that level over time, aren’t unknown. Case in point: rabies virus. Case in point: HIV-1. What matters more than whether a virus kills its host is when.
“A disease organism that kills its host quickly creates a crisis for itself,” wrote the historian William H. McNeill, in his landmark 1976 book Plagues and Peoples, “since a new host must somehow be found often enough, and soon enough, to keep its own chain of generations going.” McNeill was right, and the key word in that statement is “quickly.” Timing is all. A disease organism that kills its host slowly but inexorably faces no such crisis.
Where’s the balance point in that dynamic interplay between transmission and virulence? It differs from case to case. A virus can succeed nicely in the long term, despite killing every individual infected, if it manages to get itself passed onward to new individuals before the death of the old. Rabies does that by traveling to the brain of an infected animal—commonly a dog, a fox, a skunk, or some other mammalian carnivore, with flesh-biting habits and sharp teeth—and triggering aggressive changes of behavior. Those changes induce the mad animal to go on a biting spree. In the meantime, the virus has traveled to the salivary glands as well as the brain, and therefore achieves transmission into the bitten victims, even though the original host eventually dies or is killed with an old rifle by Atticus Finch.
Rabies also occurs sometimes in cattle and horses, but you seldom hear about that, probably because herbivores are less likely to pass the infection along with a furious bite. A poor rabid cow may let out a piteous bellow and bump into a wall, but it can’t easily skulk down a village lane, snarling and nipping at bystanders. Reports occasionally filter out of eastern Africa about rabies outbreaks in camels, which are especially worrisome to pastoralists who tend them because of the dromedary’s notorious tendency to bite. One recent dispatch from the northeastern Uganda borderlands told of a rabies-infected camel that ran mad and “started jumping up and down, biting other animals, before it died.” Another, from Sudan, mentioned that rabid camels get excitable, sometimes attacking inanimate objects or biting their own legs—which can’t do the camels much harm, not at that stage, but does reflect the strategy of the virus. Even a human in the last throes of rabies infection could potentially transmit the virus with a bite. No such case has ever been confirmed, according to WHO, but precautions are sometimes taken. There was a farmer in Cambodia, several years ago, who broke with the disease after being bitten by a rabid canine. In his late stages, the man hallucinated, he convulsed, and worse. “He barked like a dog,” his wife recalled later. “We put a chain on him and locked him up.”
HIV-1, like rabies, seems almost invariably to kill its host. It did, anyway, during the gruesome decades before combined antiretroviral therapy became available, and possibly does (time will tell) even now. Death rates have slowed among some categories of HIV-positive people (mainly those wit
h access to the expensive drug cocktails), though this doesn’t mean that the virus itself has mellowed. The HIVs by their nature are very slow-acting creatures, which is why they are lumped within the genus Lentivirus (from the Latin lentus, meaning “slow”) along with such other laggardly agents as visna virus, feline immunodeficiency virus, and equine infectious anemia virus. HIV-1 may circulate within a person’s bloodstream for ten years or more, replicating gradually, evading the body’s defenses, fluctuating in abundance, doing its damage bit by bit to the cells that mediate immune functions, before full-blown AIDS arrives with its fatal results. During that period, the virus has ample time and opportunity to get from one person to another; in the early stage of infection (when viremia goes high, before falling back down), its chances of onward transmission are especially good. More on this below, when we come to the subject of how the HIVs originally spilled over. The point here is that evolution may coax the human immunodeficiency viruses toward various changes, various adaptations, various new proclivities, but a reduction in lethality will not necessarily be one of them.
The most famous instance of a virus becoming less virulent is the case of myxoma virus among Australian rabbits. This one is literally a textbook example. Myxomatosis isn’t a zoonotic disease but it played a small, important role in helping scientists understand how virulence can be adjusted by evolution.
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The story began in the mid-nineteenth century, when a misguided white landholder named Thomas Austin had the bright idea of introducing wild European rabbits to the Australian landscape. Austin was an “ardent acclimatizer,” meaning a willful introducer of nonnative animals and plants, who had also given Australia the gift of sparrows. In 1859, a shipment of twenty-four rabbits from England reached him by boat. He wasn’t the first to bring rabbits to Australia, but he was the first to seek out wild rabbits, in preference to docile, hutch-bred representatives of the species (Oryctolagus cuniculus), which had long been domesticated. He released them on his property in Victoria, the southernmost state of Australia’s mainland. Liberated from the problems of home, still capable of life in the wild, and having a naturally high reproductive rate (they were rabbits, after all), Austin’s imports and their offspring multiplied crazily. If he had brought them over for the joy of shooting them, or hunting them with dogs, he got more than his wish. Within just six years, twenty thousand rabbits had been killed on his estate, and others had gone hopping away in all directions.
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