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

by David Quammen

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.

“We know that walking into a small woodlot,”48 he wrote, “is riskier than walking into a nearby large, extensive forest. We know that hiking in the oak woods two summers after a big acorn year is much riskier than hiking in those same woods after an acorn failure. We know that forests that house many kinds of mammals and birds are safer than those that support fewer kinds. We know that the more opossums and squirrels there are in the woods, the lower the risk of Lyme disease, and we suspect that the same is true of owls, hawks, and weasels.” As for white-tailed deer: They’re involved, yes, but far from paramount, so don’t believe everything you’ve heard.

ONE OF THE signal lessons of Lyme disease, as Rick Ostfeld and his colleagues have shown, is that a zoonosis may spill over more readily within a disrupted, fragmented ecosystem than within an intact, diverse ecosystem.

Fundamentl!

Both the round bodies of B. burgdorferi and the small form of C. burnetii merely illustrate that, even in the age of antibiotics, bacteria can be sneaky and tough. These microbes remind us that you don’t have to be a virus to cause severe, intractable, mystifying outbreaks of zoonotic disease in the twenty-first century. Although it helps.

Ivanofsky’s report, that “the sap of leaves infected with tobacco mosaic disease1 retains its infectious properties even after filtration,” constituted the first operational definition of viruses: infectious but “filterable,” meaning so small they would pass through where bacteria wouldn’t.

piece of bad news wrapped up in a protein.”

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,9 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 tolerance10 between invader and invaded.” Macfarlane Burnet agreed: In

general terms, where two organisms have developed11 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 th...

“A disease organism that kills its host quickly12 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.”

“Coevolution of Hosts and Parasites,” appeared in 1982. It began by dismissing those “unsupported statements” in medical and ecological textbooks19 “to the effect that ‘successful’ parasite species evolve to be harmless to their hosts.” Bosh and nonsense, said Anderson and May. In reality the virulence of a parasite “is usually coupled with the transmission rate and with the time taken to recover by those hosts for whom the infection is not lethal.” Transmission rate and recovery rate were two variables that Anderson and May included in their model. They noted three others: virulence (defined as deaths caused by the infectious agent), deaths from all other causes, and the ever-changing population size of the host. The best measure of evolutionary success, they figured, was the basic reproductive rate of the infection—that cardinal parameter, R0. So they had five crucial variables and they wanted to understand the net effect. They wanted to trace the dynamics. This led them to a simple equation. There will be no math questions in the quiz at the end of this book, but I thought you might like to cast your eyes upon it. Ready? Don’t flinch, don’t worry, don’t blink: 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 match showed that their model, though still crude and approximate, might help predict and explain the course of other disease outbreaks. “Our major conclusion,” wrote Anderson and May,20 “is that a ‘well-balanced’ host-parasite association is not necessarily one in which the parasite does little harm to its host.” Their italics: not necessarily. On the contrary, it depends. It depends on the specifics of the linkage between transmission and virulence, they explained. It depends on ecology and evolution.

To say Eddie Holmes wrote the book on this subject wouldn’t be metaphorical. It’s titled The Evolution and Emergence of RNA Viruses, published by Oxford in 2009, and that’s what had brought me to his door. Now he was summarizing some of the highlights.

Some of the dogs tested positive for antibodies, probably because they had been living closely with sick pigs or eating dead ones. The dogs didn’t seem to be spreading the virus much, neither from one canine to another nor to humans (though some evidence suggests that dog-to-human transmission did happen occasionally).

“Sometimes nothing happens,” Epstein said. A leap is made but the microbe remains benign in its new host, as it was in the old one. (Simian foamy virus?) In other cases, the result is very severe disease for a limited number of people, after which the pathogen comes to a dead end. (Hendra, Ebola.) In still other cases, the pathogen achieves great and far-reaching success in its new host.

“A lot of what determines whether a pathogen becomes successful in a new host, I think, is odds. Chance, to a large degree.”

Many of those viruses cause no disease, or they cause a new disease that—in some parts of the world, because health care is marginal—gets mistaken for an old disease. “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.”

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”6 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.

Among the most important things to remember about evolution—and about its primary mechanism, natural selection, as limned by Darwin and his successors—is that it doesn’t have purposes. It only has results.

“It’s all about opportunity.” They don’t come after us. In one way or another, we go to them.

HUMAN-TO-HUMAN transmission is the crux. That capacity is what separates a bizarre, awful, localized, intermittent, and mysterious disease (such as Ebola) from a global pandemic. Remember the simple equation offered by Roy Anderson and Robert May for the dynamics of an unfolding epidemic? R0 = βN/(α + b + v) In that formulation, β represents the transmission rate. β is the letter beta, in case you’re not a mathematician or a Greek. Here it’s a multiplier in the single expression that stands as numerator of the fraction, a strong position. What that means is, when β changes muchly, R0 changes muchly. And R0, your good memory tells you, is the measure of whether an outbreak will take off.

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.

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.

How does a pathogen acquire such an adaptation? The process of genetic variation (by mutation or other means) is random. A game of craps. But an abundance of opportunity helps to increase a virus’s likelihood of rolling its point—that is, chancing into a highly adaptive change. The more rolls before sevening out, the more opportunities to win. And there’s Jon Epstein’s word again: opportunity.

SO MUCH FOR where as well as when. AIDS began with a spillover from one chimp to one human, in southeastern Cameroon, no later than 1908 (give or take a margin of error), and grew slowly but inexorably from there. That leaves our third question: how?

So we’re unique in the history of mammals. We’re unique in the history of vertebrates. The fossil record shows that no other species of large-bodied beast—above the size of an ant, say, or of an Antarctic krill—has ever achieved anything like such abundance as the abundance of humans on Earth right now. Our total weight amounts to about 750 billion pounds. Ants of all species add up to a greater total mass, krill do too, but not many other groups of organisms. And we are just one species of mammal, not a group. We’re big: big in body size, big in numbers, and big in collective weight. We’re so big, in fact, that the eminent biologist (and ant expert) Edward O. Wilson felt compelled to do some knowledgeable noodling on the matter. Wilson came up with this: “When Homo sapiens passed the six-billion mark2 we had already exceeded by perhaps as much as 100 times the biomass of any large animal species that ever existed on the land.”