Spillover: Animal Infections and the Next Human Pandemic

by David Quammen

RNA viruses therefore evolve quicker than perhaps any other class of organism on Earth. It’s what makes them so volatile, unpredictable, and pesky.

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.

Professor Mohammed Mustafa Feeroz, Engel and Jones-Engel’s principal Bangladeshi collaborator, would stand as defense. Four of Feeroz’s students would help. Defense was important because the uncaptured monkeys might charge, frantic to free their comrades. They could be a formidable platoon.

🙅🏻‍♀️

Some pilgrims believed that if a monkey took food from your hand, your prayers would be answered.

Have I got a bridge to sell you!

If cases do sometimes occur in Bali, they must escape medical notice, or else get taken for some other dreadful disease, such as polio, or rabies, which is a serious problem in Bali because of its prevalence among the island’s dogs.

Knocking Bali a few spots down my travel list

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.

There are few things more terrifying than the thought of airborne rabies

The first rule of a successful parasite? Myxoma’s success in Australia suggests something different from that nugget of conventional wisdom I mentioned above. It’s not Don’t kill your host. It’s Don’t burn your bridges until after you’ve crossed them.

Duvenhage, a rabies cousin, jumps to humans from bats.

Oh good rabies has cousins

Bangladesh is at special risk from infectious disease outbreaks for several reasons, most obvious of which is the density of its population. Within its fifty-seven thousand square miles of territory it contains almost 150 million people, making it the most densely populated country in the world (apart from tiny city-states such as Singapore and Malta).

The fourth member of our party was Arif Islam, also a veterinarian, one of very few in Bangladesh who works with wildlife and zoonotic diseases, and the only member of our group who spoke fluent Bangla. Arif was crucial because he could draw blood from a bat’s brachial artery, negotiate with local officials, and order curried fish for us in a local restaurant.

“A lot of these viruses, a lot of these pathogens that come out of wildlife into domestic animals or people, have existed in wild animals for a very long time,” he said. They don’t necessarily cause any disease. They have coevolved with their natural hosts over millions of years. They have reached some sort of accommodation, replicating slowly but steadily, passing unobtrusively through the host population, enjoying long-term security—and eschewing short-term success in the form of maximal replication within each host individual. It’s a strategy that works. But when we humans disturb the accommodation—when we encroach upon the host populations, hunting them for meat, dragging or pushing them out of their ecosystems, disrupting or destroying those ecosystems—our action increases the level of risk. “It increases the opportunity for these pathogens to jump from their natural host into a new host,” he said. The new host might be any animal (the horse in Australia, the palm civet in China) but often it’s humans, because we are present so intrusively and abundantly. We offer a wealth of opportunity.

“The point being,” he said, “that the more opportunity viruses have to jump hosts, the more opportunity they have to mutate when they encounter new immune systems.” Their mutations are random but frequent, combining nucleotides in myriad new ways. “And, sooner or later, one of these viruses has the right combination to adapt to its new host.” This point about opportunity is a crucial idea, more subtle than it might seem. I had heard it from a few other disease scientists. It’s crucial because it captures the randomness of the whole situation, without which we might romanticize the phenomena of emerging diseases, deluding ourselves that these new viruses attack humans with some sort of purposefulness. (Loose talk about “the revenge of the rain forest” is one form of such romanticizing. That’s a nice metaphor, granted, but shouldn’t be taken too seriously.) Epstein was talking, in an understated way, about the two distinct but interconnected dimensions of zoonotic transfer: ecology and evolution. Habitat disturbance, bushmeat hunting, the exposure of humans to unfamiliar viruses that lurk in animal hosts—that’s ecology. Those things happen between humans and other kinds of organism, and are viewed in the moment. Rates of replication and mutation of an RNA virus, differential success for different strains of the virus, adaptation of the virus to a new host—that’s evolution. It happens within a population of some organism, as the population responds to its environment over tim...

cc: all the people going on this year about covid-19 being nature’s revenge on us

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.

Social intimacy helps too, and many kinds of bat seem to love crowding, at least when they hibernate or roost. Mexican free-tailed bats in Carlsbad Caverns, for instance, snuggle together at about three hundred individuals per square foot. Not even lab mice in an overloaded cage would tolerate that. If a virus can be passed by direct contact, bodily fluids, or tiny droplets sprayed through the air, crowding improves its chances. Under conditions like those in Carlsbad, Calisher’s group noted, even rabies has been known to achieve airborne transmission.

Oh my god WHAT I don’t want to know this 😖

rabies and its close relatives (the lyssaviruses),

how did it take me this long to learn that the rabies virus family is MY NAME

Wait a minute, lemme get this straight: 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?

Yes, David!!!

It worries the flu scientists because they know that H5N1 influenza is (1) extremely virulent in people, with a high lethality though a relatively low number of cases, and yet (2) poorly transmissible, so far, from human to human. It’ll kill you if you catch it, very likely, but you’re unlikely to catch it except by butchering an infected chicken. Most of us don’t butcher our own chickens, and health officials all over the world have been working hard to assure that the chickens we handle—dead, disarticulated, wrapped in plastic or otherwise—have not been infected. But if H5N1 mutates or reassembles itself in just the right way, if it adapts for human-to-human transmission, then H5N1 could become the biggest and fastest killer disease since 1918.

Given the global scorecard of morbidity and mortality caused by old-fashioned infectious diseases—such as cholera, typhoid, TB, rotavirus diarrhea, malaria (excepting Plasmodium knowlesi), not to mention chronic illnesses such as cancer and heart disease—why divert attention to these boutique infections, these anomalies, that spill out of bats or monkeys or who knows where to claim a few dozen or a few hundred people now and then? Why? Isn’t it misguided to summon concern over a few scientifically intriguing diseases, some of them new but of relatively small impact, while boring old diseases continue to punish humanity? After my detour through the Cholera Hospital, after being pinioned by that mother’s expectant stare, I found myself asking the same thing: Why obsess about zoonoses? In the larger balance of miseries, what makes anyone think they should be taken so seriously? It’s a fair question but there are good answers. Some of those answers are intricate and speculative. Some are subjective. Others are objective and blunt. The bluntest is this: AIDS.

As the new century began, AIDS researchers pondered this roster of different viral lineages: seven groups of HIV-2 and three groups of HIV-1. The seven groups of HIV-2, distinct as they were from one another, all resembled SIVsm, the virus endemic in sooty mangabeys. (So did the later addition, group H.) The three kinds of HIV-1 all resembled SIVcpz, from chimps. (The eventual fourth kind, group P, is most closely related to SIV from gorillas.) 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.

After his undergraduate work he went to Oxford on a Rhodes scholarship, which ordinarily means two years of mildly strenuous academic work plus lots of tea, sherry, tennis on grass, and genteel anglophilia before the “scholar” returns to professional school or a career.

😂

Okay so far? You’re doing great. Take a breath. Now those bits of understanding will boost us across a deep gulf of molecular arcana to an important scientific insight. Here we go.

We hit a police checkpoint and endured a routine but annoying shakedown, which Neville handled with aplomb, making two phone calls to influential contacts, refusing to pay the expected bribe, and yet somehow recovering our passports after only an hour. This guy is good, I thought.

“A gong is sounded,” according to a Bakwele chief who informed my source, “a voice calls out from the forest, and two chimpanzees respond. The male chimpanzee comes out first and touches the boy’s head. The female chimpanzee emerges minutes after and the boy is expected to kill it.” At dawn the boy bathes, then stays awake until late afternoon, pacing and expectant, at which point the circumciser comes at him with a homemade knife. “I nursed my wound for 45 days after,” one initiate said. But now he was a man, no longer a boy. The unpublished report added: Until recently, the Bakweles have been using chimps for this ritual. They claim two chimps could be used for circumcision of as many as 36 people. They amputate the arms of the chimps. This part of the animal is eaten by elders of the village. Of late, however, due to the scarcity of chimps, Bakweles go for gorillas.

Very confused about the relationship between the circumcision and the chimps

After dinner, my compadres and I stepped back outside and admired the sky. Although this was Saturday night, the lights of Mambele Junction didn’t amount to much and despite their dim glow we could see not just the Big Dipper, Orion’s Belt, and the Southern Cross but even the Milky Way, arcing overhead like a great smear of glitter. You know you’re in the boonies when the galaxy itself is visible downtown.

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 outbreak 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.”

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 mark and flashed past like it was a “Welcome to Kansas” sign on the highway.

“With our virus, people like to say, they’ll say, ‘Oh, you study that virus that causes the insect to explode!’ Like, the virus doesn’t cause the insect to explode,” he insisted. “It causes it to melt.”

To be fair melting doesn’t sound much better

Influenza is caused by three types of viruses, of which the most worrisome and widespread is influenza A. Viruses of that type all share certain genetic traits: a single-stranded RNA genome, which is partitioned into eight segments, which serve as templates for eleven different proteins. In other words, they have eight discrete stretches of RNA coding, linked together like eight railroad cars, with eleven different deliverable cargoes. The eleven deliverables are the molecules that comprise the structure and functional machinery of the virus. They are what the genes make. Two of those molecules become spiky protuberances from the outer surface of the viral envelope: hemagglutinin and neuraminidase. Those two, recognizable by an immune system, and crucial for penetrating and exiting cells of a host, give the various subtypes of influenza A their definitive labels: H5N1, H1N1, and so on. The term “H5N1” indicates a virus featuring subtype 5 of the hemagglutinin protein combined with subtype 1 of the neuraminidase protein. Sixteen different kinds of hemagglutinin, plus nine kinds of neuraminidase, have been detected in the natural world. Hemagglutinin is the key that unlocks a cell membrane so that the virus can get in, and neuraminidase is the key for getting back out.

Laver was such an adventurous soul that, when he finished his doctoral work in London, he and his wife drove home to Australia rather than fly.

uh

Only subtypes bearing H1, H2, or H3 as their hemagglutinin cause human flu epidemics, because only those spread readily from person to person.

“As long as H5N1 is out there in the world,” Webster said, “there is the possibility of disaster. That’s really the bottom line with H5N1. So long as it’s out there in the human population, there is the theoretical possibility that it can acquire the ability to transmit human-to-human.” He paused. “And then God help us.”

“Some of these viruses,” he warned, citing coronaviruses in particular, “should be considered as serious threats to human health. These are viruses with high evolvability and proven ability to cause epidemics in animal populations.” It’s interesting in retrospect to note that he had augured the SARS epidemic six years before it occurred.

These scientists are on alert. They are our sentries. They watch the boundaries across which pathogens spill. And they are productively interconnected with one another. When the next novel virus makes its way from a chimpanzee, a bat, a mouse, a duck, or a macaque into a human, and maybe from that human into another human, and thereupon begins causing a small cluster of lethal illnesses, they will see it—we hope they will, anyway—and raise the alarm. Whatever happens after that will depend on science, politics, social mores, public opinion, public will, and other forms of human behavior. It will depend on how we citizens respond. So before we respond, either calmly or hysterically, either intelligently or doltishly, we should understand in some measure the basic outlines and dynamics of the situation. We should appreciate that these recent outbreaks of new zoonotic diseases, as well as the recurrence and spread of old ones, are part of a larger pattern, and that humanity is responsible for generating that pattern. We should recognize that they reflect things that we’re doing, not just things that are happening to us. We should understand that, although some of the human-caused factors may seem virtually inexorable, others are within our control. The experts have alerted us to these factors and it’s easy enough to make a list. We have increased our population to the level of 7 billion and beyond. We are well on our way toward 9 billion before our growth trend is likely to f...

Ecological circumstance provides opportunity for spillover. Evolution seizes opportunity, explores possibilities, and helps convert spillovers to pandemics.

That’s the salubrious thing about zoonotic diseases: They remind us, as St. Francis did, that we humans are inseparable from the natural world. In fact, there is no “natural world,” it’s a bad and artificial phrase. There is only the world. Humankind is part of that world, as are the ebolaviruses, as are the influenzas and the HIVs, as are Nipah and Hendra and SARS, as are chimpanzees and bats and palm civets and bar-headed geese, as is the next murderous virus—the one we haven’t yet detected.

“If you hold mean transmission rate constant,” he told me, “just adding heterogeneity by itself will tend to reduce the overall infection rate.” That sounds dry. What it means is that individual effort, individual discernment, individual choice can have huge effects in averting the catastrophes that might otherwise sweep through a herd. An individual gypsy moth may inherit a slightly superior ability to avoid smears of NPV as it grazes on a leaf. An individual human may choose not to drink the palm sap, not to eat the chimpanzee, not to pen the pig beneath mango trees, not to clear the horse’s windpipe with his bare hand, not to have unprotected sex with the prostitute, not to share the needle in a shooting gallery, not to cough without covering her mouth, not to board a plane while feeling ill, or not to coop his chickens along with his ducks. “Any tiny little thing that people do,” Dwyer said, if it makes them different from one another, from the idealized standard of herd behavior, “is going to reduce infection rates.”