Spillover: Animal Infections and the Next Human Pandemic

by David Quammen

Several factors contributed to limiting the scope and the impact of the outbreak, of which humanity’s good luck was only one. Another was the speed and excellence of the laboratory diagnostics—finding the virus and identifying it—performed by Malik Peiris, Guan Yi, their partners in Hong Kong, and their colleagues and competitors in the United States, China, and Europe. Still another was the brisk efficiency with which cases were isolated, contacts were traced, and quarantine measures were instituted in southern China (after some early confusion and denial), Hong Kong, Singapore, Hanoi, and Toronto; and the rigor of infection-control efforts within hospitals, such as those overseen by Brenda Ang at Tan Tock Seng.

One further factor, possibly the most crucial, was inherent to the way SARS-CoV affects the human body: Symptoms tend to appear in a person before, rather than after, that person becomes highly infectious.

With influenza and many other diseases the order is reversed, high infectivity preceding symptoms by a matter of days. A perverse pattern: the danger, then the warning.

Everything nowadays moves around the planet faster, including viruses. If SARS had conformed to the perverse pattern of presymptomatic infectivity, its 2003 emergence wouldn’t be a case history in good luck and effective outbreak response. It would be a much darker story.

The much darker story remains to be told, probably not about this virus but about another. When the Next Big One comes, we can guess, it will likely conform to the same perverse pattern, high infectivity preceding notable symptoms. That will help it to move through cities and airports like an angel of death.

wow this aged like milk

maybe they remembered the news stories about SARS. I didn’t intrude on them with questions. I wouldn’t have noticed them at all, except they were both wearing surgical masks. Yes, I thought, if only it were that simple.

Eight decades ago he sensed that viruses, only lately discovered, might be among the most nefarious of zoonoses.

The difficulty of cultivating viruses in vitro made them obscure to early researchers, elusive in the laboratory, but it was also a clue to their essence. A virus won’t grow in a medium of chemical nutrients because it can only replicate inside a living cell.

Viruses face four basic challenges: how to get from one host to another, how to penetrate a cell within that host, how to commandeer the cell’s equipment and resources for producing multiple copies of itself, and how to get back out—out of the cell, out of the host, on to the next. A virus’s structure and genetic capabilities are shaped parsimoniously to those tasks.

The capsid serves two purposes: It protects the viral innards when they need protection and it helps the virus lever its way into cells.

The individual viral unit, one particle, standing intact outside a cell, is called a virion.

Viruses, from the beginning of virology, have been defined in the negative (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.

Variation is the raw material upon which natural selection operates.

“Infection” need not always entail any significant damage; the word merely means an established presence of some microbe.

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.

Herpes B is a very rare infection in humans but a nasty one, with a case fatality rate of almost 70 percent among those few dozen people infected during the twentieth century (before recent breakthroughs in antiviral pharmaceutics) and almost 50 percent even since then.

When it doesn’t kill, it often leaves survivors with neurological damage. It’s an occupational hazard of scientists and technicians who work with laboratory macaques. Among the macaques themselves it’s common, but merely an annoyance.

Not so with herpes B in people. In the decades since Brebner’s death, forty-two other human cases have been diagnosed, all involving scientists or laboratory technicians or other animal-handlers who had contact with macaques in captivity.

In the 1980s came a small second uptick in herpes B incidents, correlated with another increase in the use of macaques, this time for research on AIDS.

Meanwhile, cultures taken from swabbing her eyes were quietly retrieved from the commercial laboratories to which they had been sent for analysis—um, never mind, we’ll just take those back. Her cultures had belatedly been deemed too dangerous for ordinary lab workers to handle.

The probability of cross-species transmission might be low—very low, under normal circumstances—but the consequences were high.

This decision was driven by the fact that Britain’s Advisory Committee on Dangerous Pathogens had lately reclassified herpes B into biohazard level 4, placing it in the elite company of Ebola, Marburg, and the virus that causes Crimean-Congo hemorrhagic fever.

A more sensitive question, raised by primatologists who considered such cullings grotesque and unnecessary, was whether herpes B does or doesn’t belong in level 4. Some arguments suggest that it doesn’t.

As the chainsaws and machetes of humanity’s advance guard have driven them out of their native forest habitats—in India, Southeast Asia, Indonesia, and the Philippines—they have been only more willing to take their chances scavenging, stealing, and panhandling at the edges of civilization.

Lisa Jones-Engel, chief genius of the whole project but prohibited from entering this shrine because of her gender, would be waiting in a courtyard nearby, along with several female assistants, to begin drawing blood.

One, two, three: trap, tranquilize, draw. What could be simpler? Lots of things, let me tell you, could be simpler.

In both cases, the virus is often lethal to humans but not nearly so consequential as it would be if not constrained by the limits of its transmissibility. It has no preternatural powers. It finds humans a dead-end host. People are ignorant about its actual properties and inclined to imagine an unreal breadth of risk. Among differences between the two, there’s this: Ebola is infamous and herpes B is largely unknown. It’s unknown, that is, unless you work in a monkey lab or run a safari park.

However dangerous herpes B might be when infecting a person, the chances of monkey-human transmission seem to be extremely small.

Evidently the virus is not easily transmitted, and evidently it’s not causing subtle, asymptomatic infections among people in close contact with monkeys.

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.

The Next Big One, as I mentioned at the start of this book, is a subject that disease scientists around the world often address. They think about it, they talk about it, and they’re quite accustomed to being asked about it. As they do their work or discuss pandemics of the past, the Next Big One (NBO) is at the back of their minds.

Moral: If you’re a thriving population, living at high density but exposed to new bugs, it’s just a matter of time until the NBO arrives. Note that most of these big ones but not all of them (plague the exception) were viral. Now that modern antibiotics are widely available, vastly reducing the lethal menace of bacteria, we can guess confidently that the Next Big One will be a virus too.

To understand why some outbreaks of viral disease go big, others go really big, and still others sputter intermittently or pass away without causing devastation, consider two aspects of a virus in action: transmissibility and virulence.

Transmissibility and virulence: the yin and yang of viral ecology.

Pathogenicity is the capacity of a microbe to cause disease. Virulence is the measurable degree of such disease, especially as gauged against other strains of similar pathogen.

Even a human in the last throes of rabies infection could potentially transmit the virus with a bite. No such case has ever been confirmed, according to WHO, but precautions are sometimes taken.

They detected a wide diversity of strains and, for purposes of analysis, they grouped those strains into five distinct grades of Australian myxoma, on a descending scale of lethality. Grade I was the original strain, with its case fatality rate of nearly 100 percent; grade II killed upward of 95 percent; grade III, the intermediate among all five, still killed between 70 and 95 percent of infected rabbits. Grade IV was milder, and grade V milder still (though far from harmless), killing less than 50 percent of the rabbits it infected.

After a decade, Fenner and his partners discovered, grade III myxoma had come to predominate. It was still causing upward of 70 percent mortality among the rabbits, and it constituted more than half of all the samples collected. The most lethal strain (grade I) had nearly disappeared, and the most benign strain (grade V) was still rare. The situation seemed to have stabilized.

Don’t burn your bridges until after you’ve crossed them.

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.

It depends on the specifics of the linkage between transmission and virulence, they explained. It depends on ecology and evolution.

Two reasons for that, he explained. It’s not just the high mutation rates but also the fact that their population sizes are huge. “Those two things put together mean you’ll produce more adaptive change.”

The downside for DNA viruses, Eddie said, is that they can’t adapt so readily to a new species of host.

RNA viruses are limited to small genomes because their mutation rates are so high, and their mutation rates are so high because they’re limited to small genomes. In fact, there’s a fancy name for that bind: Eigen’s paradox.

His paradox describes a size limit for such self-replicating molecules, beyond which their mutation rate gives them too many errors and they cease to replicate.

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.

All this confirmed pigs as an amplifier host of the same Nipah virus that was killing humans. But it said nothing about where Nipah might ultimately reside.

the virus seemed to be extraordinarily contagious, at least among swine, even when it wasn’t extraordinarily virulent.

So pigs were far more hospitable and tolerant amplifiers than the poor horses, in Australia, who came down with Hendra.