Spillover: Animal Infections and the Next Human Pandemic

by David Quammen

Most DNA viruses embody the opposite extremes. Their mutation rates are low and their population sizes can be relatively small. Their strategies of self-perpetuation “tend to go for this persistence route,” Eddie said. Persistence and stealth. They lurk, they wait. They hide from the immune system rather than trying to outrun it. They go dormant and linger within certain cells, replicating little or not at all, sometimes for many years.

What do you do if you’re a virus that’s stuck, with no long-term security, no time to waste, nothing to lose, and a high capacity for adapting to new circumstances? By now we had worked our way around to the point that interested me most. “They jump species a lot,” Eddie said.

So there’s a certain diversity of origins. But 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.

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.

Another perceived starting point was 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 Africa 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.

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. 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.

So: It was infinitesimal, contagious, blood-borne. “AIDS could not be caused by a conventional bacterium, a fungus, or protozoan,” Montagnier wrote, “since these kinds of germs are blocked by the filters through which the blood products necessary to the survival of hemophiliacs are passed. That left only a smaller organism: the agent responsible for AIDS thus could only be a virus.”

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.

Our estimation of divergence times, with an evolutionary timescale spanning several decades, together with the extensive genetic distance between DRC60 and ZR59 indicate that these viruses evolved from a common ancestor circulating in the African population near the beginning of the twentieth century. To me he said: “This wasn’t a new virus in humans.” Worobey’s work directly refuted the OPV hypothesis. If HIV-1 existed in humans as early as 1908, then obviously it hadn’t been introduced via vaccine trials beginning in 1958.

The work appeared in Nature, highlighted by a commentary calling it “the most persuasive evidence yet that HIV-1 came to humans from the chimpanzee, Pan troglodytes.” In fact, Gao and his colleagues did more than trace HIV-1 to the chimp; their analysis of viral strains linked it to individuals of a particular subspecies known as the central chimpanzee (Pan troglodytes troglodytes), whose SIV had spilled over to become HIV-1 group M. That chimpanzee lives only in western Central Africa, north of the Congo River and west of the Oubangui. So the Gao study effectively identified both the reservoir and also the geographical area from which AIDS must have arisen. It was a huge discovery, as reflected in the headline of Nature’s commentary: FROM PAN TO PANDEMIC.

Hahn’s lab had located the geographical origin of the pandemic.

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?

“The likeliest route of chimpanzee-to-human transmission would have been through exposure to infected blood and body fluids during the butchery of bushmeat.” A man kills a chimpanzee and dresses it out, hacks it up, in the course of which he suffers blood-to-blood contact through a cut on his hand. SIVcpz passes across the species boundary, from chimp to human, and taking hold in the new host becomes HIV-1.

One man in southeastern Cameroon is infected. “If the spillover occurred there,” I asked Hahn, “how was it that the epidemic began in Kinshasa?” “Well, there are lots of rivers going down from that region to Kinshasa,” she said. “And the speculation, the hypothesis, is that is how the virus traveled—in people, not in apes. It wasn’t the apes that got into the canoe for a little visit of Kinshasa. It was the people who carried the virus down, most likely.” Sure, she acknowledged, there was a slim chance that someone might have brought a live chimp, captive, infected, all the way down from the Cameroonian wedge—“but I think it is highly unlikely.” More likely the virus traveled in humans. Sexual contacts in the villages kept the chain of infection alive, though barely, by this line of speculation, and the disease didn’t explode as a notable outbreak—not for a long while.

When someone died of immune deficiency, the death may have seemed unremarkable amid all other sources of mortality. Life was hard, life was perilous, life expectancy was short even apart from the new disease, and many of those earliest HIV-positive people may have succumbed to other causes before their immune systems failed. There was no epidemic. But the chain of infection sustained itself. R0 remained greater than 1.0. The virus seems to have traveled just as people traveled in those days: mainly by river. It made its way out of southeastern Cameroon along the headwaters of the Sangha, then down the Sangha to the Congo, then down the Congo to Brazzaville and Léopoldville, the two colonial towns on either side of what then was still known as the Stanley Pool. “Once it got into an urban population,” Hahn said, “it had an opportunity to spread.” But still it moved slowly, like a locomotive just leaving the station. Léopoldville contained fewer than ten thousand people in 1908, and Brazzaville was even smaller. Sexual mores and the fluidity of interactions were unlike what prevailed in the boondocks, but not yet so unlike as they would become. R0 for the virus must have continued to hover around 1.0. Time passed and more people drifted into the towns, drawn by the prospect of working for wages or selling their goods. Habits and opportunities changed. Women came as well as men, though not so many of them, and among those who did, more than a few entered the sex trade.

Free women had their special friends, their clients, maybe several contemporaneously, but there was no dizzying permutation of multiple sexual contacts, not yet. One expert has called this “a low-risk type of prostitution,” with regard to the prospects of HIV transmission.

The tenfold population increase, along with the concomitant changes in social relations, might go a long way to explain why HIV “suddenly” took off.

In that case, the meat would have been parceled out retail and many people may have eaten bits of it, either roasted or smoked or dried. But 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.

People died of malaria. People died of tuberculosis. People died of pneumonia. People died of nameless fever. It was routine. Some of those people might have recovered, had their immune systems been capable, but no one noticed a new disease. Or if someone did notice, the report hasn’t survived. This thing remained invisible. Meanwhile the virus itself may have adapted, at least slightly, to its new host. It mutated often. Natural selection was at work. Given a marginal increase in its capacity to replicate within human cells, leading to increased levels of viremia, its efficiency of transmission may have increased too.

Very interesting literary choice to commit several chapters’ worth of space to fictional narrative

African monkeys have carried their SIV infections for a very long time—probably millions of years. That length of time would allow divergence among the viruses and mutual accommodation between each type of virus and its host.

So the very existence of SIVcpz is relatively recent. It has no ancient association with chimpanzees. And now, based on a study published in 2009, part two of the two-part hypothesis has also been cast into doubt. The virus is not so harmless in its chimpanzee host. Evidence from the chimps of Gombe—Jane Goodall’s study population, known and beloved around the world—suggests that SIVcpz causes simian AIDS.

this reflected a risk of death ten times to sixteen times higher for SIV-positive chimps than for SIV-negatives.

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. 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.

A famous French colonial doctor named Eugène Jamot, working just east of the upper Sangha River (in a portion of French Equatorial Africa then known as Oubangui-Chari) during 1917–1919, treated 5,347 trypanosomiasis cases using only six syringes. This sort of production-line delivery of injectable medicines didn’t allow time for boiling a syringe and needle between uses.

All those injections, according to Pepin, might account for boosting the incidence of HIV infection beyond a critical threshold. Once the reusable needles and syringes put the virus into enough people—say, several hundred—it wouldn’t come to a dead end, it wouldn’t burn out, and sexual transmission could do the rest.

The more virions, the more mutations; the more mutations, the more diversity.

One thing that happened was that, from a single HIV-positive person in 1966 or thereabouts, the virus spread fast through the Haitian population.

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 also bounced back to Africa. It was HIV globalized.

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. So it lurked here for more than a decade before anyone noticed.

It was no longer a chimpanzee virus. It had found a new host and adapted, succeeding brilliantly, passing far beyond the horizons of its old existence within chimpanzees. It reached hemophiliacs through the blood supply. It reached drug addicts through shared needles. It reached gay men—reached deeply and catastrophically into their circles of love and acquaintance—by sexual transmission, possibly from an initial contact between two males, an American and a Haitian.

Outbreak in the broader sense applies to any vast, sudden population increase by a single species. Such outbreaks occur among certain animals but not among others.

As of last week, I said, we’ve got 7 billion humans on this planet. It seems like an outbreak population. We live at high densities. Look at Hong Kong, look at Mumbai. We’re closely interconnected. We fly around. The 7 million people in Hong Kong are only three hours away from the 12 million people in Beijing. No other large animal has ever been as abundant. And we’ve also got our share of potentially devastating viruses. Some of those might be as nasty as NPV. So . . . what’s the prognosis? Is it valid, The Analogy? Should we expect to crash like a population of gypsy moths?

The Next Big One could very well be flu. Greg Dwyer knew this, which is why he mentioned it. I’m sure you don’t need reminding that the 1918–1919 flu killed about 50 million people; and there’s still no magical defense, no universal vaccine, no foolproof and widely available treatment, to guarantee that such death and misery don’t occur again. Even during an average year, seasonal flu causes at least 3 million cases and more than 250,000 fatalities worldwide. So influenza is hugely dangerous, at best. At worst, it would be apocalyptic.

That’s why influenza is such a protean sort of bug, always full of surprises, full of newness, full of menace: so much mutation and reassortment. The steady incidence of mutations yields incremental change in how the virus looks and behaves. Ergo you need another flu shot every autumn: This year’s version of flu is different enough from last year’s. Reassortment yields big changes.

We provide an irresistible opportunity for enterprising microbes by the ubiquity and abundance of our human bodies.

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