Spillover: the powerful, prescient book that predicted the Covid-19 coronavirus pandemic.

by David Quammen

At the Chatou market in Guangzhou, for instance, he had seen storks, seagulls, herons, cranes, deer, alligators, crocodiles, wild pigs, raccoon dogs, flying squirrels, many snakes and turtles, many frogs, as well as domestic dogs and cats, all on sale as food. There were no civets, not when he saw the place; they had already been demonized and purged. The list he recited was just a selection, from memory and from his own discreet inspections, of what food markets were offering then. You could also buy leopard cat, Chinese muntjac, Siberian weasel, Eurasian badger, Chinese bamboo rat, butterfly lizard, and Chinese toad, plus a long list of other reptiles, amphibians, and mammals, including two kinds of fruit bat. Quite an epicure’s menu. And of course birds: cattle egrets, spoonbills, cormorants, magpies, a vast selection of ducks and geese and pheasants and doves, plovers, crakes, rails, moorhens, coots, sandpipers, jays, several flavors of crow. One fellow, a Chinese colleague of Aleksei’s, told me that the bird-and-bat trade was covered by an adage: “People in south China will eat everything that flies in the sky, except an airplane.” He was a northerner himself.

I don't even know most of these animals!

SARS in 2003 was an outbreak, not a global pandemic. Eight thousand cases are relatively few, for such an explosive infection; 774 people died, not 7 million. Several factors contributed to limiting the scope and the impact of the outbreak, of which humanity’s good luck was only one. Another was the speed and excellence of the laboratory diagnostics—finding the virus and identifying it—performed by Malik Peiris, Guan Yi, their partners in Hong Kong, and their colleagues and competitors in the United States, China, and Europe. Still another was the brisk efficiency with which cases were isolated, contacts were traced, and quarantine measures were instituted in southern China (after some early confusion and denial), Hong Kong, Singapore, Hanoi, and Toronto; and the rigor of infection-control efforts within hospitals, such as those overseen by Brenda Ang at Tan Tock Seng. If the virus had arrived in a different sort of big city—more loosely governed, full of poor people, lacking first-rate medical institutions—it might have escaped containment and burned through a much larger segment of humanity. One further factor, possibly the most crucial, was inherent to the way SARS-CoV affects the human body: Symptoms tend to appear in a person before, rather than after, that person becomes highly infectious. The headache, the fever, and the chills—maybe even the cough—precede the major discharge of virus toward other people. Even among some of the superspreaders, in 2003, this seems to...

Why SARS didn't become a pandemic

Lyme disease, psittacosis, Q fever: These three differ wildly in their particulars but share two traits in common. They are all zoonotic and they are all bacterial. They stand as reminders that not every bad, stubborn, new bug is a virus.

Over those twenty years, mammal by mammal, tick by tick, Ostfeld and his team collected an enormous body of information, and the work continues. They use Sherman live traps (from the H. B. Sherman company, of Tallahassee, a venerable supplier) baited with oats and set out on the forest floor. They release most of the captured animals alive, after a brief examination to check body condition and remove ticks. Small mammal biologists like him, for whom trap-and-release protocols are the daily routine of data gathering, tend to become highly adept—gentle but efficient—at handling live rodents. Ostfeld’s group has found that, in about one minute of close scrutiny, they can detect 90 percent of the ticks on a mouse. (They measured their own field-exam thoroughness by taking some mice into captivity after the one-minute checkover, holding them captive, and waiting for all ticks to fall off into a pan of water beneath the cage. Then they sorted the ticks from the mouse shit and other detritus—“a messy and challenging task,”44 Ostfeld testified—and counted this fuller total for comparison with what had been seen in the field.) For chipmunks, the method of quick visual inspection worked almost as well. On other small mammals, including squirrels and shrews, the tick burdens were higher and harder to count, but Ostfeld’s group could still make well-informed estimates. Larval ticks are minuscule and even a tiny masked shrew, weighing only five grams (about the same as two dimes), carr...

Tick census!

Like an insect, the blacklegged tick undergoes metamorphosis, passing through two immature stages (larva and nymph) on the way to adulthood. At each of those stages, it needs a single blood meal from a vertebrate host to nourish its transmogrification; an adult tick needs another blood meal to supply energy and protein for reproduction. In most cases the vertebrate host is a mammal, though it might also be a lizard, or a ground-nesting bird such as the veery, exposing itself to larval ticks on the forest floor. The blacklegged tick is such a generalist, in fact, that its menu of known hosts includes more than a hundred North American vertebrates, ranging from robins to cows, from squirrels to dogs, from skinks to skunks, from possums to people. “These ticks are unbelievably catholic in their tastes,” Ostfeld told me. An adult female tick spends her winter with a bellyful of blood and then in spring lays her eggs, which hatch into larvae by midsummer. Whether as immatures or as adults, ticks can’t travel very quickly or very far. They don’t fly. They’re not so acrobatic as fleas or springtails. They lumber around like tiny tortoises. But they seem to be “exquisitely sensitive” to chemical and physical signals,45 according to Ostfeld, and thereby “able to orient toward safe locations for overwintering and toward hosts emitting carbon dioxide and infrared radiation.” They smell out their food. They may not be agile, but they’re opportunistic, alert, and ready. The complete li...

The terrific ticks

White-tailed deer seem to play a much different role. They are important mainly to adult ticks—not just for their blood, but also for providing a venue where male blacklegged ticks can meet females. A whitetail in the woods of Connecticut, during November, is like a teeming singles’ bar in lower Manhattan on Friday night, crowded with lubricious seekers. One poor doe might be carrying a thousand mature blacklegged ticks. Mating occurs, somewhat gracelessly, when a male tick, prowling across the skin of the deer, encounters a preoccupied female—she is tapped in, drinking, immobile. Don’t look for romance in arachnoid sex. Once the female has had her drink, and the male has had his congress, they drop off the deer, making way for others. Given such turnover, during a four-week season of tick procreation, a single whitetail can supply blood for the production of 2 million fertilized tick eggs. If half of those hatch, it’s a million larvae from one deer.

Mating of ticks

Borrelia burgdorferi infection doesn’t pass vertically between blacklegged ticks. In plainer language: It is not inherited. Of those million baby ticks, all derived from the female ticks that fed on a single deer, none will be carrying B. burgdorferi when they hatch—not even if every mother tick was infected and the deer was too. The youngsters will come into the world clean and healthy. Each generation of ticks must be infected anew. Generally what seems to happen is that a larval tick acquires the spirochete by taking its blood meal from an infected host—a mouse, a shrew, a whatever. It molts to become a nymph and then, if it gets its next meal from an uninfected host, the nymph passes the infection to that animal, by drooling spirochetes into the wound along with its anticoagulant saliva. “If mammals didn’t make ticks sick,” Ostfeld said, “ticks wouldn’t make mammals sick later on.” Such reciprocal infectivity helps keep the prevalence of B. burgdorferi high in both tick populations and hosts.

Lyme bacteria is non-inheritable

“reservoir competence.”47 This is the measure of likelihood that a given host animal, if it’s already infected, will transmit the infection to a feeding tick. Reservoir competence varies from species to species, most likely depending on differences in the strength of immune response against the pathogen. If the immune response is weak and the blood teems with spirochetes, that species will serve as a highly “competent” reservoir of B. burgdorferi, transmitting infection to most ticks that bite it. If the immune response is strong and effective, damping down the level of blood-borne spirochetes, that species will be a relatively less competent reservoir.

Say you’re a parent with young children, living here in your Millbrook dream house on three acres of beautiful lawn and shrubbery—what do you want for protection against Lyme disease? There might be a whole range of desperate options. Pesticide spraying by the county? Deer eradication by the state? Thousands of mousetraps (not Shermans but the lethal kind), deployed in the forest and baited with cheese, snapping away like brushfire? Do you pave your yard and ring it with an oil-filled moat? Do you put flea-and-tick collars on your kids’ ankles before they go out to play? No, none of those. “I would feel a lot more comfortable,” Ostfeld answered, “if I knew that the landscape would support healthy populations of owls, foxes, hawks, weasels, squirrels of various kinds—the components of the community that could regulate mouse populations.” In other words, biological diversity. This was his offhand way of expressing the most notable conclusion that has emerged from twenty years of research: Risk of Lyme disease seems to go up as the roster of native animals, in a given area, goes down. Why? Probably because of the differences in reservoir competence between mice and shrews (both with high competence) and almost all other vertebrate hosts (low competence) that may share habitat with them. The effect of the most competent reservoirs is diluted by the presence, when there is such presence, of less-competent alternatives. In forest patches containing a full cast of ecological play...

How to contain Lyme disease

The mouse is a good colonizer, a good survivor, a fecund breeder, an opportunist; it is there to stay. Restrained by few predators and few competitors, its population fluctuates around a relatively high average level and, in summers following a big acorn crop, goes much higher still. A plague of mice will infest the little woodland, like rats on the road out of Hamelin. There will also be plenty of ticks. The ticks drink heartily of mouse blood and have a high rate of survival, because white-footed mice (unlike possums, catbirds, or even chipmunks) are not very good at grooming themselves clear of larvae. And because the mouse is such a competent reservoir of Borrelia burgdorferi—so efficient at harboring and transmitting it—most ticks carry the infection. In a larger area of forest, with a more richly diverse community of animals and plants, the dynamics are different. Facing a dozen or more kinds of predators and competitors, the white-footed mouse is less numerous; the other mammals are less competent as hosts for the spirochete and less tolerant of thirsty tick larvae; the net effect is fewer infected ticks.

Small ecosystem = less ecological diversity = MORE dangerous

Why so elusive? Because viruses are vanishingly minuscule, simple but ingenious, anomalous, economical, and in some cases fiendishly subtle. Expert opinion even divides on the conundrum of whether viruses are alive. If they aren’t, then at the very least they’re mechanistic shortcuts on the principle of life itself. They parasitize. They compete. They attack, they evade. They struggle. They obey the same basic imperatives as all living creatures—to survive, to multiply, to perpetuate their lineage—and they do it using intricate strategies shaped by Darwinian natural selection. They evolve. The viruses on Earth today are well fit for what they do because only the fittest have survived.

I love viruses!

Whatever the shape, the interior volume is minuscule. The genomes packed within such small containers are correspondingly limited, ranging from 2,000 nucleotides up to about 1.2 million. The genome of a mouse, by contrast, is about 3 billion nucleotides. It takes three nucleotide bases to specify an amino acid and on average about 250 amino acids to make a protein (though some proteins are much larger). Making proteins is what genes do; everything else in a cell or a virus results from secondary reactions. So a genome of just two thousand code letters, or even thirteen thousand (as for the influenzas) or thirty thousand (the SARS virus), is a very sketchy set of engineering specs. Even with such a small genome, though, coding for just eight or ten proteins, a virus can be wily and effective.

Viruses pack a punch, given their tininess

Viruses face four basic challenges: how to get from one host to another, how to penetrate a cell within that host, how to commandeer the cell’s equipment and resources for producing multiple copies of itself, and how to get back out—out of the cell, out of the host, on to the next. A virus’s structure and genetic capabilities are shaped parsimoniously to those tasks.

Virology 101 from here on...

it generally repairs mistakes in the placement of bases as it replicates itself. This repair work is performed by DNA polymerase, the enzyme that helps catalyze construction of new DNA from single strands. If an adenine is mistakenly set in place to become linked with a guanine (not its correct partner), the polymerase recognizes that mistake, backtracks by one pair, fixes the mismatch, and then moves on. So the rate of mutation in most DNA viruses is relatively low. RNA viruses, coded by a single-strand molecule with no such corrective arrangement, no such buddy-buddy system, no such proofreading polymerase, sustain rates of mutation that may be thousands of times higher.

RNA viruses mutate far more than DNA viruses

not every virus is “a piece of bad news wrapped up in a protein”—or at least, it’s not bad news for every host infected. Sometimes the news is merely neutral. Sometimes it’s even good; certain viruses perform salubrious services for their hosts. “Infection” need not always entail any significant damage; the word merely means an established presence of some microbe. A virus doesn’t necessarily achieve anything by making its host sick. Its self-interest requires just replication and transmission. The virus enters cells, yes, and subverts their physiological machinery to make copies of itself, yes, and often destroys those cells as it exits, yes; but maybe not so many cells as to cause real harm. It may inhabit a host rather quietly, benignly, replicating at modest levels and getting transmitted from one individual to another without producing any symptoms. The relationship between a virus and its reservoir host, for instance, tends to involve such a truce, sometimes reached after long association and many generations of mutual evolutionary adjustment, the virus becoming less virulent, the host becoming more tolerant. That’s in part what defines a reservoir: no symptoms. Not every virus-host relationship evolves toward such amicable relations. It’s a special form of ecological equilibrium.

Beyond the obvious point that it might cause an unknown disease, Engel and Jones-Engel have another reason for studying this virus. “It’s a marker,” Gregory told me. “We caught a marker for transmission,” Lisa echoed. What they meant is that the presence of SFV within a human population marks opportunities having occurred for cross-species infection of all kinds. If simian foamy has made the leap from a half-tame macaque to a person—to several people, maybe to thousands of people passing through sites such as Sangeh—then so could other viruses, their presence still undetected, their effects still unknown. “And why is that important?” I asked. “Because we’re looking for the Next Big One,” she said.

A benign virus might provide information for other sinister ones

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.

We're sitting ducks

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.

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.

The other being, virulence

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 virus need not be benign to be successful

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,13 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.14 “We put a chain on him and locked him up.”

Rabies is fucked uup!

Frank Fenner guessed astutely that it was the dynamic between virulence and transmission. His tests of one grade versus another, using captive rabbits and captive mosquitoes, revealed that the efficiency of transmission correlated with the amount of virus available on a rabbit’s skin. More lesions, or lesions that lasted longer, meant more available virus. More virus smeared on mosquito mouthparts, more chance of transmission to the next rabbit. But “available virus” assumed that the rabbit was still alive, still pumping warm blood, and therefore still of interest to the vector. Dead, cold rabbits don’t attract mosquitoes. Between the two extreme outcomes of infection—healed rabbits and dead rabbits—Fenner found a point of balance. “Laboratory experiments showed that all field strains17 produced lesions that provided sufficient virus for transmission to occur,” he wrote. But the strains of very high virulence (grades I and II) killed rabbits “so quickly that infectious lesions were only available for a few days.” The milder strains (grades IV and V) produced lesions that tended to heal quickly, he added—and then the payoff, “whereas strains of grade III virulence were highly infectious for the lifetime of the rabbits that died and for a much longer period in those that survived.” Grade III, at that point, was still killing around 67 percent of the rabbits it touched. Myxoma virus, thirty years after its introduction, had found this level of virulence—being pretty damn leth...

Australian rabbit virus story: Virus lethality and evolutionary success

R0 = βN/(α + b + v) In English: The evolutionary success of a bug is directly related to its rate of transmission through the host population and inversely but intricately related to its lethality, the rate of recovery from it, and the normal death rate from all other causes. (The clunky imprecision of that sentence is why ecologists prefer math.)

Viral success, expressed mathematically

why are RNA genomes so small? Because their self-replication is so fraught with inaccuracies that, given more information to replicate, they would accumulate more errors and cease to function at all. It’s sort of a chicken-and-egg problem, he said. RNA viruses are limited to small genomes because their mutation rates are so high, and their mutation rates are so high because they’re limited to small genomes. In fact, there’s a fancy name for that bind: Eigen’s paradox. Manfred Eigen is a German chemist, a Nobel winner, who has studied the chemical reactions that yield self-organization of longer molecules, a process that might lead to life. His paradox describes a size limit for such self-replicating molecules, beyond which their mutation rate gives them too many errors and they cease to replicate. They die out. RNA viruses, thus constrained, compensate for their error-prone replication by producing huge populations and achieving transmission early and often. They can’t break through Eigen’s paradox, it seems, but they can scoot around it, making a virtue of their instability. Their copying errors deliver beaucoup variation, and beaucoup variation allows them to evolve fast.

a large fraction of all the scary new viruses I’ve mentioned so far, as well as others I haven’t mentioned, come jumping at us from bats. Hendra: from bats. Marburg: from bats. SARS-CoV: from bats. Rabies, when it jumps into people, comes usually from domestic dogs—because mad dogs get more opportunities than mad wildlife to sink their teeth into humans—but bats are among its chief reservoirs. Duvenhage, a rabies cousin, jumps to humans from bats. Kyasanur Forest virus is vectored by ticks, which carry it to people from several kinds of wildlife, including bats. Ebola, very possibly: from bats. Menangle: from bats. Tioman: from bats. Melaka: from bats. Australian bat lyssavirus, it may not surprise you to learn, has its reservoir in Australian bats. And though the list already is long, a little bit menacing, and in need of calm explanation, it wouldn’t be complete without adding Nipah, one of the more dramatic RNA viruses to emerge within recent decades, which leaps into pigs and via them into humans: from bats.

Bats are something to be reckoned with

The Malaysian government in the meantime had ordered a mass culling—that is, the extermination of every pig, infected or uninfected, on every farm that the outbreak had touched. Some of those piggeries had been abandoned by their operators, panicky and bewildered, even before the discovery of the new virus. People in certain areas even fled their homes; Sungai Nipah became a ghost town. By the end of the outbreak, at least 283 humans had been infected and 109 had died, for a case fatality rate of almost 40 percent. Nobody wanted to eat pork, or to handle it, or to buy it. Pigs were left starving in their pens. Some broke out to roam the roadways like feral dogs, foraging for food. Malaysia at that time contained 2.35 million pigs, half of them from Nipah-affected farms, so this could have become an almost medieval problem, like a scene from the Black Death: herds of infected pigs stampeding ravenously through empty villages. A phalanx of cullers, including soldiers from the army as well as police and veterinary officers, moved into the countryside wearing protective suits, gloves, masks, and goggles. Their assigned task was to shoot, bury, or otherwise dispose of more than a million animals, and to do it quickly, without splashing virus everywhere. Despite all precautions, at least half a dozen soldiers did get infected. Hume Field noted: “There’s no easy way to kill a million pigs.”

Taking care of Nipah

One possibility is that Field had in mind other potential zoonoses that are simmering, unrecognized, presently harmless to humans, among domesticated animals. How many such bugs may be working their way through large-scale livestock operations around the globe? How many RNA viruses may be achieving high rates of evolution (because they replicate quickly, they mutate often, their populations are big, and the herds are big too) in our factory farms? What are the odds, given such numbers, of a mutation that facilitates spillover? How many other Nipahs are slouching toward Bethlehem to be born?

Scary

Bacterial pneumonia, for instance, accounts for about ninety thousand deaths annually just among Bangladeshi children under age five. Bacterial diarrhea kills about twenty thousand newborn infants every year. Given those numbers, I asked Luby, why divert any attention at all to Nipah? To be prudent, he said. Classic case of the devils you know versus the devil you don’t know, none of which can you afford to ignore. Nipah is important because of what might happen and because we understand little about how it might happen. “This is a horrible pathogen,” he said, reminding me that the lethality among Nipah cases in Bangladesh is more than 70 percent. “Of those who survive, a third of them have marked neurological deficits. This is a bad disease.”

Why new diseases, seemingly having lesser impact, also need to be paid attention to

The tappers are known as gachis, tree people, from the Bangla word gach, meaning “tree.” Other people own the palms, and the owners typically get a half share of the product. The gachis are poor, independent operators, generally agricultural laborers who do this as a seasonal sideline. To harvest sap, a gachi climbs a tree, shaves away a large patch of bark near the top to create a V-shaped bare patch (from which sap oozes out), places a hollow bamboo tap at the base of the V, and hangs his small clay pot beneath the tap. The sap flows overnight; the pot fills. Just before dawn, the gachi climbs up again and brings down a pot of fresh sap. Maybe he gets two liters per tree. Bounty! Those two liters are worth about twenty takas (US $0.24) if he can sell them before 10 a.m. He empties the clay pot into a larger aluminum vessel, mixing the sap and the bat feces (if any) and the bat urine (if any) and the virus (if any) from one tree with the sap (and its impurities) from others. Then off he goes to sell his product. Some gachis are complacent about the risk of adulteration. One told a colleague of Luby’s: “I do not see any problem, if birds drink sap from my trees. Because birds drink a slight amount of sap. I would get God’s grace by giving bats and other animals a chance to drink sap.” He gets God’s grace and the customer gets Nipah. Other gachis do care, because clear reddish sap brings a better price than foamy, gunky sap full of drowned bees, bird feathers, and bat shit.

Transmission of Nipah

what is the deal with bats? The paper made a handful of salient points, the first of which put the rest in perspective: Bats come in many, many forms. The order Chiroptera (the “hand-wing” creatures) encompasses 1,116 species, which amounts to 25 percent of all the recognized species of mammals. To say again: One in every four species of mammal is a bat. Such diversity might suggest that bats don’t harbor more than their share of viruses; it could be, instead, that their viral burden is proportional to their share of all mammal diversity, and thus just seems surprisingly large. Maybe their virus-per-bat ratio is no higher than ratios among other mammals. Then again, maybe it is higher.

"Bats: Important Reservoir Hosts" continues throughout the chapter...

You’re in a cave in Uganda, surrounded by Marburg and rabies and black forest cobras, wading through a slurry of dead bats, getting hit in the face by live ones like Tippi Hedren in The Birds, and the walls are alive with thirsty ticks, and you can hardly breathe, and you can hardly see, and … you’ve got time to be claustrophobic? “Uganda is not famous for its mine rescue teams,” he said.

Working in one of the CDC’s BSL-4 units, Towner and his co-workers had isolated viable, replicating Marburg virus from five different bats. Furthermore, the five strains of virus were genetically diverse, suggesting an extended history of viral presence and evolution within Egyptian fruit bats. Those data, plus the fragmentary RNA, constituted strong evidence that the Egyptian fruit bat is a reservoir—if not the reservoir—of Marburg virus. Based on the isolation work, it’s definitely there in the bats. Based on the RNA fragments, it seems to infect about 5 percent of the bat population at a given time. Putting those numbers together with the overall population estimate of a hundred thousand bats at Kitaka, the team could say that about five thousand Marburg-infected bats flew out of the cave every night. An interesting thought: five thousand infected bats passing overhead. Where were they going? How far to the fruiting trees? Whose livestock or little gardens got shat upon as they went? Jon Epstein’s advice would have been apt: “Keep your mouth closed when you look up.” And the Kitaka aggregation, Towner and his coauthors added, “is only one of many such cave populations11 throughout Africa.

Marburg is found in bats

she began talking about susceptible individuals, infected individuals, and recovered individuals in a given bat population. If the population is isolated and insufficiently large, then the virus will move through it, infecting the susceptibles and leaving them recovered (and immune to reinfection), until there are virtually no susceptibles left. Then it will die out, just as measles dies out in an isolated human village. Eventually the virus will return, brought back to that population by a wayward, infected bat. This represents the same blinking-Christmas-light pattern that I invoked with regard to Marburg. The ecologists call it a metapopulation: a population of populations. The virus avoids extinction by infecting one relatively isolated population of bats after another. It dies out here, it arrives and infects there; it may not be permanently present in any one population but it’s always somewhere. The lights blink off/on in their turns, never all lit, never all dark. If the bat populations are separated by distances great enough that those distances are seldom crossed, then the rate of reinfection is slow. The lights blink off and on languidly. Now imagine one such bat population within the metapopulation. It has progressed through the SIR sequence, every individual infected, every one recovered, and the virus is gone. But not gone forever. As years pass, as the birth of new bats and the death of old ones raise back the proportion of susceptibles, the population regai...

Metapopulations and the Christmas light analogy of pathogenic propagation

Nipah was passing horizontally through the community, like a rumor, not just down from the sky, like a divine curse or a dollop of bat poop. And its seeming ubiquity was confirmed by one other finding of the combined response team. This bit of data was especially spooky. The investigators took swabs from the wall of a hospital room in which one of the patients had been treated, five weeks earlier, and from the soiled frame of a bed in which that patient had lain. None of those surfaces had been cleaned in the meantime; bleach and labor were in short supply. Some swabs, both from the wall and the bed frame, tested positive for Nipah RNA. I’ll repeat that: Fragments (at least) of Nipah virus, left from what the patient had spewed out, were still present after five weeks, invisibly decorating the room. To the sanitarian, such spewing represents contamination. To the virus: opportunity.

Viruses are a hardy breed

Gaëtan Dugas, the young Canadian flight attendant who became notorious as “Patient Zero.” You’ve heard of him, probably, if you’ve heard much of anything about the dawning of AIDS. Dugas has been written about as the man who “carried the virus out of Africa3 and introduced it into the Western gay community.” He wasn’t. But he seems to have played an oversized and culpably heedless role as a transmitter during the 1970s and early 1980s. As a flight steward, with almost cost-free privileges of personal travel, he flew often between major cities in North America, joining in sybaritic play where he landed, notching up conquests, living the high life of a sexually voracious gay man at the height of the bathhouse era. He was handsome, sandy-haired, vain but charming, even “gorgeous” in some eyes.4 According to Randy Shilts, author of And the Band Played On (which includes much heroic research and a fair bit of presumptuous reimagining), Dugas himself reckoned that in the decade since becoming actively gay he had had at least twenty-five hundred sexual partners. Dugas paid a price for his appetite and his daring. He developed Kaposi’s sarcoma, underwent chemotherapy for that, suffered from Pneumocystis pneumonia and other AIDS-related infections, and died of kidney failure at age thirty-one. During the brief stretch of years between his Kaposi’s diagnosis and his final invalidism, Gaëtan Dugas didn’t slow down. But he seems to have tipped, in his lonely despair, from hedonism to ...

Satan says calm down

Retroviruses are fiendish beasts, even more devious and persistent than the average virus. They take their name from the capacity to move backward (retro) against the usual expectations of how a creature translates its genes into working proteins. Instead of using RNA as a template for translating DNA into proteins, the retrovirus converts its RNA into DNA within a host cell; its viral DNA then penetrates the cell nucleus and gets itself integrated into the genome of the host cell, thereby guaranteeing replication of the virus whenever the host cell reproduces itself.

The sooty mangabey (Cercocebus atys) is a smoky-gray creature with a dark face and hands, white eyebrows, and flaring white muttonchops, not nearly so decorative as many monkeys on the continent but arresting in its way, like an elderly chimney sweep of dapper tonsorial habits.

Loved the description

Now here’s the part that, as it percolates into your brain, should cause a shudder: Scientists think that each of those twelve groups (eight of HIV-2, four of HIV-1) reflects an independent instance of cross-species transmission. Twelve spillovers. In other words, HIV hasn’t happened to humanity just once. It has happened at least a dozen times—a dozen that we know of, and probably many more times in earlier history. Therefore it wasn’t a highly improbable event. It wasn’t a singular piece of vastly unlikely bad luck, striking humankind with devastating results—like a comet come knuckleballing across the infinitude of space to smack planet Earth and extinguish the dinosaurs. No. The arrival of HIV in human bloodstreams was, on the contrary, part of a small trend. Due to the nature of our interactions with African primates, it seems to occur pretty often.

base-by-base comparisons between DRC60 and ZR59. It also involved broader comparisons, placing those two within a family tree of known sequences of HIV-1 group M. The point of such comparisons was to see how much evolutionary divergence had occurred. How far had these strains of virus grown apart? Evolutionary divergence accumulates by mutation at the base-by-base level (other ways too, but those aren’t relevant here), and among RNA viruses such as HIV, as I’ve explained, the mutation rate is relatively fast. Equally important, the average rate of HIV-1 mutation is known—or anyway, it can be carefully estimated from the study of many strains. That rate of mutation is considered the “molecular clock” for the virus. Every virus has its own rate, and therefore its own clock measuring the ticktock of change. The amount of difference between two viral strains can therefore reveal how much time has passed since they diverged from a common ancestor. Degree of difference factored against clock equals elapsed time. This is how molecular biologists calculate an important parameter they call TMRCA: time to most recent common ancestor.

Viral dating

For use elsewhere, the urine-screening method wasn’t practical. “Because, you know, nonhabituated chimps don’t stay close enough so you can catch their pee.” You could collect their poop from the forest floor, of course, but fecal samples were useless unless preserved somehow; fresh feces contain an abundance of proteases, digestive enzymes, which would destroy the evidence of viral presence long before you got to your laboratory. These are the constraints within which a molecular biologist studying wild animals labors: the relative availability and other parameters of blood, shit, and piss.

Chasing blood, shit and piss

Just outside Mr. Munga’s office, I paused in the corridor to look at a wall poster with lurid illustrations and a warning in French: LA DIARRHEA ROUGE TUE! The red diarrhea kills. At first glance I thought that referred to Ebola, but no. “Grands Singes et VIH/ SIDA,” read the finer print. SIDA is the French acronym for AIDS, and VIH likewise is HIV. The cartoonish but unfunny drawings depicted a stark parable about the connection between simian bushmeat and la diarrhea rouge. I lingered long enough for the oddness to strike me. Throughout the rest of the world you see AIDS-education materials crying out: Practice safe sex! Wear a condom! Don’t reuse needles! Here the message was: Don’t eat apes!

The chimpanzee’s virus entered his bloodstream. He got a sizable dose. The virus, finding his blood to be not such a different environment from the blood of a chimp, took hold. Okay, I can live here. It did what a retrovirus does: penetrated cells, converted its RNA genome into double-stranded DNA, then penetrated further, into the cells’ nuclei, and inserted itself as DNA in the DNA genome of those host cells. Its primary targets were T cells of the immune system. A certain protein receptor (CD4) on the surface of those cells, in the Cut Hunter, was not very different from the equivalent receptor (another CD4) on the T cells of the butchered chimpanzee. The virus attached, entered the human cells, and made itself at home. Once integrated into the cellular genome, it was there for good. It was part of the program. It could proliferate in two ways: by cell replication (each time an infected T cell copied itself, the retroviral genome was copied also) and by activating its little subgenome to print off new virions, which then escaped from the T cell and floated off to attack other cells. The Cut Hunter was now infected, though apart from a slash on the hand he felt fine.

How SIV would have probably taken hold the first time

because of how the virus generally achieves transmission (blood-to-blood or sexually) and how it doesn’t (through the gastrointestinal tract), quite possibly none of those people received an infectious dose of virus, unless by contact of raw meat with an open cut on the hand or a sore in the mouth. A person might swallow plenty of HIV-1 particles but, if those virions are greeted by stomach acids and not blood, they would likely fail to establish themselves and replicate.

the AIDS pandemic is traceable to a single contingent event. That this event involved a bloody interaction between one chimpanzee and one human. That it occurred in southeastern Cameroon, around the year 1908, give or take. That it led to the proliferation of one strain of virus, now known as HIV-1 group M. That this virus was probably lethal in chimpanzees before the spillover occurred, and that it was certainly lethal in humans afterward. That from southeastern Cameroon it must have traveled downriver, along the Sangha and then the Congo, to Brazzaville and Léopoldville. That from those entrepôts it spread to the world.

The AIDS story in a nutshell

Marx’s group even argued that serial passage of HIV through people, by means of such injection campaigns, might have accelerated the evolution of the virus and its adaptation to humans as a host, just as passaging malarial parasites through 170 syphilis patients (remember the crazed Romanian researcher, Mihai Ciuca?) could increase the virulence of Plasmodium knowlesi.

Woah!

Plasma, the liquid component of blood (minus the cells), is valuable stuff for its antibodies and albumin and clotting factors. Demand for it rose sharply during the period around 1970, and to meet the demand a process called plasmapheresis was developed. Plasmapheresis entails drawing blood from a donor, separating the cells from the plasma by means of filtering or centrifuging, putting the cells back into the donor, and keeping the plasma as a harvested product. One advantage of this process is that it allows donors (who are usually in fact sellers, paid for their trouble and needing the money) to be tapped often rather than just a couple times per year. Giving up your plasma, for the good of others or for profit, doesn’t leave you anemic. You can go back and give again the following week. One disadvantage of the procedure—and it’s a huge one, but wasn’t recognized in the early days—is that a plasmapheresis machine, gargling your blood and the blood of many other donors over the course of days, can infect you with a blood-borne virus.

Plasma donation and HIV

An entomologist named Alan A. Berryman addressed it some years ago in a paper titled “The Theory and Classification of Outbreaks.” He began with basics: “From the ecological point of view an outbreak1 can be defined as an explosive increase in the abundance of a particular species that occurs over a relatively short period of time.” Then, in the same bland tone, he noted: “From this perspective, the most serious outbreak on the planet earth is that of the species Homo sapiens.” Berryman was alluding, of course, to the rate and the magnitude of human population growth, especially within the last couple centuries. He knew he was being provocative. But the numbers support him. At the time Berryman wrote, in 1987, the world’s human population stood at 5 billion. We had multiplied by a factor of about 333 since the invention of agriculture. We had increased by a factor of 14 since just after the Black Death, by a factor of 5 since the birth of Charles Darwin, and by doubling within the lifetime of Alan Berryman himself. That growth curve, on a coordinate graph, looks like the southwest face of El Capitan. Another way to comprehend it is this: From the time of our beginning as a species (about 200,000 years ago) until the year 1804, human population rose to a billion; between 1804 and 1927, it rose by another billion; we reached 3 billion in 1960; and each net addition of a billion people, since then, has taken only about thirteen years. In October 2011, we came to the 7-billion...

The human outbreak

A trillion pounds of cows, fattening in feedlots and grazing on landscapes that formerly supported wild herbivores, are just another form of human impact. They’re a proxy measure of our appetites, and we are hungry. We are prodigious, we are unprecedented. We are phenomenal. No other primate has ever weighed upon the planet to anything like this degree. In ecological terms, we are almost paradoxical: large-bodied and long-lived but grotesquely abundant. We are an outbreak.

He wore round tortoiseshell glasses and a black T-shirt printed with a grotesquely complex integral equation. Above and below the equation, the shirt asked in large letters: WHAT PART OF [this gobbledygook] DON’T YOU UNDERSTAND? The shirt was a metajoke, he explained to me. The gobbledygook was one of Maxwell’s equations; the joke part, of course, was that no average person would understand the thing at all; the meta part, I think, was that Maxwell’s equations are famous but so notoriously abstruse that even a mathematician might not recognize this one. Get it?

LMAO

The packets of virus lay besmeared on a leaf, left there after the death of a previous caterpillar victim. A healthy caterpillar comes munching along and swallows packets with the leaf tissue. Once inside the caterpillar, a packet unfolds, sinister and orderly, like a MIRV warhead releasing its little nukes over a city. The virions disperse, attacking cells in the caterpillar’s gut. Each virion goes to the cell nucleus (again, hence the name), replicates abundantly, generating new virions that exit the cell and proceed to attack others. “They go from cell to cell, and infect lots and lots of cells,” Dwyer said. Before long the caterpillar is essentially just a crawling and eating bag of virus. Still, it doesn’t act sick. It doesn’t seem to know how sick it is. “If it has eaten a big enough dose,” he said, “then it will continue to wander around on leaves and continue to feed—but after maybe ten days, maybe two weeks, sometimes even as long as three weeks, it will melt onto a leaf.” There was that word again, the same one he had used in Atlanta, exquisitely vivid: melt. Other caterpillars meanwhile are suffering the same fate. “The virus has almost completely consumed them before they really stop functioning.” Late in this process, as the virions within each caterpillar begin crowding one another, running short of food, they get themselves bundled together again within protective packets. Time to emerge. Time to move on. The caterpillar at this point is filled with virus, c...

The caterpillar melting NPV