Spillover: Animal Infections and the Next Human Pandemic

by David Quammen

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.

They had built their work on the same sort of conceptual schema used by disease theorists for sixty years, the SIR model, representing a flow of individuals, during the course of an outbreak, through those three classes I mentioned earlier: from susceptible (S) to infected (I) to recovered (R).

Almost all earlier disease theorists, such as Ronald Ross in 1916, Kermack and McKendrick in 1927, and George MacDonald in 1956, had treated population size as a constant.

Let’s treat population size as a dynamic variable, they proposed. Let’s get beyond assuming any artificial, inherent stability and recognize that a disease outbreak itself may affect population size—by killing a large fraction of the populace, say, or by lowering the birth rate, or by increasing societal stresses (such as overcrowding in hospitals) that might raise the rate of death from other causes.

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.

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.

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?

The larger meaning of Nipah, in accord with Hume Field’s “intriguing thought,” is that tomorrow’s pandemic zoonosis may be no more than “a blip on the productivity output” of some livestock industry today.

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.

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.

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.

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 time.

One in every four species of mammal is a bat.

When a bat lineage split into two new species, their passenger viruses may have split with them, yielding more kinds of virus as well as more kinds of bat.

The abundance, survival, and range of a virus all depend upon other organisms and what those do. That’s viral ecology. In the case of Hendra, to take another instance, the changing ecology of the virus may partly account for its emergence as a cause of human disease.

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.

No one, as of this writing, has isolated any live ebolavirus from a bat—and virus isolation is still the gold standard for identifying a reservoir.

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.

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.

Their ecstatic practices offended the conventionally pious believers around them, and so when the leader died of a brief, mysterious illness, and then his family and followers started dying too, neighbors attributed the deaths to asmani bala: a curse from above.

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.

Another perceived starting point was Gaëtan Dugas, the young Canadian flight attendant who became notorious as “Patient Zero.”

Dugas himself was infected by some other human, presumably during a sexual encounter—and not in Africa, not in Haiti, somewhere closer to home. That was possible because, as evidence now shows, HIV-1 had already arrived in North America when Gaëtan Dugas was a virginal adolescent.

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.

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.

Unlike the Asian macaques, the African green monkeys “must have evolved mechanisms that kept a potentially lethal pathogen from causing disease,” Essex and Kanki wrote.

“A plausible interpretation of these data,” Hirsch and her coauthors added, to make the point plainly, “is that in the past 30–40 years SIV from a West African sooty mangabey (or closely related species) successfully infected a human and evolved as HIV-2.” It was official: HIV-2 is a zoonosis.

HIV-2 is both less transmissible and less virulent than HIV-1.

People infected with HIV-2 tend to carry lower levels of virus in their blood, to infect fewer of their sexual contacts, and to suffer less severe or longer-delayed forms of immune deficiency. Many of them don’t seem to progress to AIDS at all. And mothers who carry HIV-2 are less likely to pass it to their infants.

HIV-1 is the thing that afflicts tens of millions of people throughout the world. HIV-1 is the pandemic scourge.

Group M was the most widespread and nefarious. The letter M stood for “main,” because that group accounted for most of the HIV infections worldwide.

Group O was the second to be delineated, its initial standing for “outlier,” because it encompassed only a small number of viral isolates, mostly traceable to what seemed an outlier area relative to the hotspots of the pandemic: Gabon, Equatorial Guinea, and Cameroon, all in western Central Africa.

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

ZR59 proved that HIV-1 had been present—simmering, evolving, diversifying—in the population of Léopoldville by 1959.

HIV-1 group M might have entered the human population around 1931.

the AIDS virus has been present in humans for decades longer than anyone thought. The pandemic may have gotten its start with a spillover as early as 1908.

Smallpox vaccine administered to kids in Camden, New Jersey, at the start of the twentieth century, seems to have been contaminated with tetanus bacillus, resulting in the death of nine vaccinated children from tetanus.

iatrogenic infection (disease caused by medical treatment)

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.

Well, one section of genome differed by 12 percent between the two versions. And how different was that, measured in time? About fifty years’ worth, Worobey figured. More precisely, he placed the most recent common ancestor of DRC60 and ZR59 in the year 1908, give or take a margin of error.

AIDS began with a spillover from one chimp to one human, in southeastern Cameroon, no later than 1908

Instead there were single women, known as ndumbas in Lingala and femmes libres in French, “free women” as distinct from wives or daughters, who would provide their clients with a suite of services, ranging from conversation to sex to washing clothes and cooking. One such ndumba might have just two or three male friends who returned on a regular basis and kept her solvent. Another variant was the ménagère, a “housekeeper” who lived with a white colonial official and did more than keep house.

The chimp virus contains genetic material from the virus of red-capped mangabeys and also genetic material from the virus of greater spot-nosed monkeys. How did it happen? By recombination—that is, genetic mixing. A chimpanzee infected with both monkey viruses must have served as the mixing bowl in which two viruses traded genes. And when did it happen? Possibly just hundreds of years ago, rather than thousands or tens of thousands.

Hahn, with a new set of concerns and methods, to which she quickly became attuned. At a scientific meeting that brought primate researchers together with virologists, she met Richard Wrangham, of Harvard, highly respected for his work on the behavioral ecology and evolution of apes.

Here’s what you have come to understand. That 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.

During the first year of independence, half the teachers sent by UNESCO to the Congo were Haitians. By 1963, according to one estimate, a thousand Haitians were employed in the country.

At least one of those returnees, probably among the earliest of them, seems to have carried HIV-1. More specifically: Someone brought back to Haiti, along with Congolese memories, a dose of HIV-1 group M subtype B.

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.

This study by Gilbert and Worobey and their colleagues delivered one other piquant finding. Their data and analysis indicated that just a single migration of the virus—one infected person or one container of plasma—accounted for bringing AIDS to America. That sorry advent occurred in 1969, give or take about three years.

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.