Spillover: Animal Infections and the Next Human Pandemic

by David Quammen

zoonosis is an animal infection transmissible to humans.

photosynthesis. Predators are relatively big beasts that eat their prey from outside. Pathogens (disease-causing agents, such as viruses) are relatively small beasts that eat their prey from within.

When a pathogen leaps from some nonhuman animal into a person, and succeeds there in establishing itself as an infectious presence, sometimes causing illness or death, the result is a zoonosis.

Monkeypox is a disease similar to smallpox, caused by a virus closely related to variola.

A reservoir host (some scientists prefer “natural host”) is a living organism that carries the pathogen, harbors it chronically, while suffering little or no illness.

To reside undetected within a reservoir host is probably easiest wherever biological diversity is high and the ecosystem is relatively undisturbed. The converse is also true: Ecological disturbance causes diseases to emerge. Shake a tree, and things fall out.

Nearly all zoonotic diseases result from infection by one of six kinds of pathogen: viruses, bacteria, fungi, protists (a group of small, complex creatures such as amoebae, formerly but misleadingly known as protozoans), prions, and worms.

like Kurt Vonnegut’s infectious form of water, ice-nine, in his great early novel Cat’s Cradle.

Viruses have no locomotion,” according to the eminent virologist Stephen S. Morse, “yet many of them have traveled around the world.” They can’t run, they can’t walk, they can’t swim, they can’t crawl. They ride.

becomes an intermediate link between a reservoir host and some other unfortunate animal, some other sort of victim—a victim requiring higher doses or closer contact before the infection can take hold. You can understand this in terms of thresholds. The amplifier host has a relatively low threshold for becoming infected, yet it produces a vast output of virus, vast enough to overcome the higher threshold in another animal.

Make no mistake, they are connected, these disease outbreaks coming one after another. And they are not simply happening to us; they represent the unintended results of things we are doing. They reflect the convergence of two forms of crisis on our planet. The first crisis is ecological, the second is medical. As the two intersect, their joint consequences appear as a pattern of weird and terrible new diseases, emerging from unexpected sources and raising deep concern, deep foreboding, among the scientists who study them. How do such diseases leap from nonhuman animals into people, and why do they seem to be leaping more frequently in recent years?

the matter in its starkest form: Human-caused ecological pressures and disruptions are bringing animal pathogens ever more into contact with human populations, while human technology and behavior are spreading those pathogens ever more widely and quickly. There are three elements to the situation.

One: Mankind’s activities are causing the disintegration (a word chosen carefully) of natural ecosystems at a cataclysmic rate. We all know the rough outlines of that problem. By way of logging, road building, slash-and-burn agriculture, hunting and eating of wild animals (when Africans do that we call it “bushmeat” and impute a negative onus, though in America it’s merely “game”), clearing forest to create cattle pasture, mineral extraction, urban settlement, suburban sprawl, chemical pollution, nutrient runoff to the oceans, mining the oceans unsustainably for seafood, climate change, international marketing of the exported goods whose production requires any of the above, and other “civilizing” incursions upon natural landscape—by all such means, we are tearing ecosystems apart. This much isn’t new. Humans have been practicing most of those activities, using simple tools, for a very long time. But now, with 7 billion people alive and modern technology in their hands, the cumulative impacts are becoming critical. Tropical forests a...

geographical range. Ebola and Marburg and Lassa and monkeypox and the precursors

history. Most people don’t know that the real, full story of AIDS doesn’t begin among American homosexuals in 1981, or in a few big African cities during the early 1960s, but at the headwaters of a jungle river called the Sangha, in southeastern Cameroon, half a century earlier. Even fewer people have caught wind of the startling discoveries that, just within the past several years, have added detail and transformative insight to that story.

primates, have done that also. Plasmodium knowlesi

So forget about deer abundance. White-tailed deer are involved in the Lyme disease system, yes, but involved like a trace element, a catalyst. Their presence is important but their numerousness is not. The littler mammals are far more critical in determining the scale of disease risk to people. Adventitious years of big acorn crops, yielding population explosions of mice and chipmunks, are more likely to influence the number of Lyme disease cases among Connecticut children than anything that deer hunters may do. Beyond helping the blacklegged tick (infected or uninfected) to survive, white-tailed deer are almost irrelevant to Lyme disease epidemiology. They don’t magnify the prevalence of infection in the forest. They don’t pass the spirochete to humans or to newly hatched ticks. They’re dead-end hosts, Ostfeld told me.

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.

it may cause. Useful as they are to a virus, though, the spikes also represent points of vulnerability. They are the primary targets of immune response by an infected host. Antibodies, produced by white blood cells, are molecules that glom onto the spikes and prevent a virion from grabbing a cell.

(not captured by a filter, not cultivable in chemical nutrients, not quite alive), and the most fundamental negative axiom is that a virion is not a cell. It doesn’t function the way a cell functions; it doesn’t share the same capacities or frailties. That’s reflected in the fact that viruses are impervious to antibiotics—chemicals valued for their ability to kill bacteria (which are cells) or at least impede their growth. Penicillin works by preventing bacteria from building their cell walls. So do its synthetic alternatives, such as amoxicillin. Tetracycline works by interfering with the internal metabolic processes by which bacteria manufacture new proteins for cell growth and replication. Viruses, lacking cell walls, lacking internal metabolic processes, are oblivious to the effects of such killer drugs. Inside the viral capsid is usually nothing

That’s in part what defines a reservoir: no symptoms. Not every virus-host relationship evolves toward such amicable relations.

scratching or biting or drool or needlestick accident or splashed urine—herpes B didn’t make the monkey-human leap. Why not? Apparently this virus isn’t ready. Another way of saying that: Ecology has provided opportunities, but evolution hasn’t yet seized them. Maybe it never will. 61

and about its primary mechanism,

“Bats: Important Reservoir Hosts”

that their viral burden is proportional

Hilary Koprowski—a lesser-known competitor in the same vaccine-development race that engaged Salk and Sabin—arranged for his candidate vaccine to be widely administered in areas of the eastern Belgian

“The origin of the AIDS virus is of no importance to science today.” He quoted another expert, William Haseltine of Harvard, as saying: “It’s distracting, it’s nonproductive, it’s confusing to the public, and I think it’s grossly misleading in terms of getting to the solution of the problem.”

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. This happened to hundreds of paid plasma donors in Mexico during the mid-1980s. It happened to a quarter million luckless donors in China. Jacques Pepin thinks it happened in Haiti too. He found reports of a plasmapheresis center in Port-au-Prince, a private business known as Hemo Caribbean, that operated profitably during 1971 and 1972. It was owned by an American investor, a man named Joseph B. Gorinstein, based in Miami, with links to the Haitian Minister of the Interior. Donors received $3 per liter. Their vitals were checked before they could sell plasma, but of course nobody screened them for HIV—which didn’t yet exist as an acronym, or an infamous global scourge, only as a quiet little virus that lived in blood. According to an article that ran in The New York Times on January 28, 1972, Hemo Caribbean was then exporting between five and six thousand liters of frozen blood plasma to the United States each month. The wholesale customers were American compani...

was molecular phylogenetics at work. In this case, the tree represented the diversified lineage of HIV-1 group M subtype B. Its major limbs represented the virus as known from Haiti. One of those limbs encompassed a branch from which grew too many small twigs to portray. So in the figure as eventually published, that branch and its twigs were blurred—depicted simply as a solid cone of brown, like a sepia shadow, within which appeared a list of names. The names told where subtype B had gone, after passing through Haiti: the United States, Canada, Argentina, Colombia, Brazil, Ecuador, the Netherlands, France, the United Kingdom, Germany, Estonia, South Korea, Japan, Thailand, and Australia. It had

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.

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. Okay so far? Having absorbed this simple paragraph,