Most of this, thank goodness, was for Jim Desmond’s benefit, not mine. Arif and Pitu and Gofur were seasoned pros; they didn’t need another briefing. Desmond was the real trainee, and I was along to watch. I didn’t intend to let anyone hand me a Nipah-dripping bat if I could reasonably avoid it.
Just outside the compound wall, in another empty building, Epstein had established his field lab. There, in the early wee hours, he and his crew readied their equipment for later tasks: anaesthetizing captured bats, taking blood samples and urine swabs from each animal, centrifuging the blood tubes to allow aliquoting off the serum, and freezing all the samples in a liquid-nitrogen shipper tank. This room had a concrete floor, barred windows, a wooden table now covered with plastic sheeting, and a sterilizing footbath at the door, through which we would come and go in our rubber boots. Epstein issued respirator masks, safety goggles, and medical gloves (not latex, not rubber, but the latest material of choice: nitrile) to everyone, and we suited up. He and Desmond both donned old coveralls. Arif had a nice new Tyvek one-piece suit, like gleaming white footie pajamas. Get something else when you can, Epstein told him gently; these bats are visual, remember, not echolocators, and they can see you. Desmond tried on his respirator, and after a moment Epstein asked, “Can you breathe?”
“Yeah.”
“That’s good. You’re not allowed to pass out. That’s rule number five.” I tried to remember the other four.
Just before pulling his own mask into place, Epstein noted cheerily: “With new and emerging viruses, it’s all about prevention. Once you have the virus, there’s not much you can do.” He handed me a small packaged wipe, like the alcohol-laced face fresheners you get on an airplane, except instead of alcohol this thing contained benzalkonium chloride. Ooo, thanks. It was now 2:40 a.m., time to go to the roof.
“All right,” he said. “Are we ready?”
74
There was no moon. We marched out through the darkness like Ghostbusters and took turns climbing the long bamboo ladder. The roof of the warehouse was a little spooky in itself, an expanse of tarpaper with a few patches and cracks, old and neglected, not guaranteed to support a person’s weight. Wearing safety glasses that quickly became fogged with vapor leaking up from my respirator, I could scarcely see where I was walking. Worse still, I could scarcely see where the building ended and open space began. About all I could see was Arif, moving around in his Tyvek, pale and diaphanous as Casper the Friendly Ghost. Okay, him we won’t bust. But don’t get distracted, and watch where you step. Rule number six, I realized, is Don’t fall off the roof.
The bats were all out for their nightly feeding. We would lurk here to catch them as they returned, sometime before daylight. Gofur and Pitu had already hoisted the net into place, an invisible wall of delicate mesh in the blackness somewhere above us, big as the screen for a drive-in movie. We hunkered down to wait. The night grew chilly—the first time in my limited Bangladesh experience I’d had occasion to get cold. I lay on my back upon the tarpaper, bundled as best I could be in a light jacket, and went to sleep. The first bat hit the net at 4:22 a.m.
Headlamps came alight, people jumped up, Gofur lowered the net on its pulleys while Epstein and Pitu converged on the animal and I staggered forward after them, safely blinded behind my safety glasses. Pitu untangled the bat and Epstein accepted it, using just the technique he had described: grabbing its head firmly, taking its legs and arms into his finger gaps—binga, binga, binga, binga—and then jouncing the bat into its bag. Close the bag’s neck, tie firmly with a piece of twine. Captured bats, like captured snakes, evidently relax better if you confine them in soft cloth. Reraise the net and repeat. I was impressed by the proficiency of Epstein’s team.
Between the first bat and daylight, before call to prayer even sounded from the local mosques, they bagged five more. Six bats for a night’s work was below par for Epstein—he liked to average about ten—but it was a good start for a new location. Adjustments to the net placement, to the height of the masts, would improve the yield here in coming days. For now, enough. As dawn filtered in, we climbed down the ladder and repaired to the laboratory room. Here again, everybody had an assigned role. Mine was to stay the hell out of the way, and occasionally to assist with a swab.
Three hours later, blood samples drawn, swab samples taken, tubes in the freezer tank, it was time to release the bats. Each of them first received a drink of fruit juice to help restore bodily fluids lost in the blood draw. Then we all walked back to the grassy courtyard, beneath the karoi trees, where a small crowd of men, women, and children from the neighborhood had gathered. (The walls of the old depot compound were permeable to locals when something interesting was afoot.) Epstein, again now wearing welder’s gloves, released the first five bats one by one from their bags, holding each animal high so it wouldn’t crawl up his face, letting it free its legs and its wings, then relaxing his grip gently just as the wing beats began to find purchase on air, and watching—all of us watching—the animal catch itself short of the ground, rise slowly, circle languidly, and fly away. Eventually, after a circuit or two of the compound, a few minutes of befuddled relief, it would find its way back to the communal roost, sadder but wiser and no great harm done.
Before releasing the last bat, Epstein gave a brief talk to the assembled citizens, translated by Arif, congratulating them on their good fortune as a village at harboring so many wonderful bats, which are helpful to fruit trees and other plants, and assuring them that he and his colleagues had taken great care not to harm the animals while studying their health. Then he let the final bat drop. It climbed through the air, from knee level, and flew away.
Later he said to me: “Any one of those six bats could have been infected. That’s what it looks like. They look totally healthy. There’s no way to distinguish Nipah virus. That’s why we take all these precautions.” He dipped his boots again in the sterile footbath, as we left the lab, and washed up at the village pump. A little girl brought soap.
75
“The key is connectivity,” Epstein told me, during a quiet chat the following afternoon. “The key is to understand how animals and people are interconnected.” We were back at the hotel, showered and fed, after another full night of trapping, another fifteen bats sampled and released. You can’t look at a new bug or a reservoir host, he said, as though they exist in a vacuum. It’s a matter of contact with humans, interaction, opportunity. “Therein lies the risk of spillover.”
Repeatedly over the next half hour he returned to the word “opportunity.” It kept knocking. “A lot of these viruses, a lot of these pathogens that come out of wildlife into domestic animals or people, have existed in wild animals for a very long time,” he said. They don’t necessarily cause any disease. They have coevolved with their natural hosts over millions of years. They have reached some sort of accommodation, replicating slowly but steadily, passing unobtrusively through the host population, enjoying long-term security—and eschewing short-term success in the form of maximal replication within each host individual. It’s a strategy that works. 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. “It increases the opportunity for these pathogens to jump from their natural host into a new host,” he said. The new host might be any animal (the horse in Australia, the palm civet in China) but often it’s humans, because we are present so intrusively and abundantly. We offer a wealth of opportunity.
“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. It finds itself well enough suited to get a foothold;
it makes itself still better suited by adapting. It evolves, it flourishes, it continues. The history of HIV is the story a leaping virus that might have come to a dead end but didn’t.
Yes, HIV is a vivid example, I agreed. But is there any particular reason why other RNA viruses shouldn’t have the same potential? For instance, Nipah?
“No reason at all. There’s no reason at all,” Epstein said. “A lot of what determines whether a pathogen becomes successful in a new host, I think, is odds. Chance, to a large degree.” With their high rates of mutation, their high rates of replication, RNA viruses are very adaptable, he reminded me, and every spillover presents a new opportunity to adapt and take hold. We’ll probably never know how often that occurs—how many animal viruses spill into people inconspicuously. 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.” Their mutations are random but frequent, combining nucleotides in myriad new ways. “And, sooner or later, one of these viruses has the right combination to adapt to its new host.”
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” 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. It happens within a population of some organism, as the population responds to its environment over time. 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. To believe otherwise is to embrace a teleological fallacy that carries emotive appeal (“the revenge of the rain forest”) but misleads. This is what Jon Epstein was getting at. Don’t imagine that these viruses have a deliberate strategy, he said. Don’t think that they bear some malign onus against humans. “It’s all about opportunity.” They don’t come after us. In one way or another, we go to them.
But what is it about bats? I asked. Why do so many of these zoonotic viruses—or what seems like so many—spill over onto humans from the chiropteran order of mammals? Or is that the wrong question?
“It is the right question,” he said. “But I don’t think there’s a good answer for it yet.”
76
There may not be a good answer, but efforts have been made. I’ve put the same question—why bats?—to emerging-disease experts around the world. One of them was Charles H. Calisher, an eminent virologist recently retired as professor of microbiology at Colorado State University.
Calisher came out of the Georgetown School of Medicine with a PhD in microbiology in 1964. He made his bones doing classic lab-table virology, which meant growing live viruses, passaging them experimentally through mice and cell cultures, looking at them in electron micrographs, figuring out where to place them on the viral family tree—the kind of work that Karl Johnson had done on Machupo, and that traced back before Johnson to Frank Fenner and Macfarlane Burnet and others still earlier. Calisher’s career included a long stretch at the CDC as well as academic appointments, during which he had focused on arthropod-borne viruses (aka arboviruses, such as West Nile, dengue, and La Crosse virus, all carried by mosquitoes) and rodent-borne viruses (notably the hantaviruses). As a scientist who studied viruses in their vectors and in their reservoirs for more than four decades, but with no particular attention to chiropterans, he too eventually found himself wanting to know: Why are so many of these new things emerging from bats?
Charlie Calisher is a smallish man with a dangerous twinkle, famed throughout the profession for his depth of knowledge, his caustic humor, his disdain for pomposity, his brusque manner, and (if you happen to get past those crusts) his big, affable heart. He insisted on buying me lunch, at a favorite Vietnamese restaurant in Fort Collins, before we got down to serious talk. He wore a fisherman’s sweater, chinos, and hiking boots. After the meal I followed his red pickup truck back to a CSU laboratory compound, where he still had a few projects going. He pulled a flat-sided flask from an incubator, put it under a microscope, focused, and said, Look here: La Crosse virus. I saw monkey cells, in a culture medium the color of cherry Kool-Aid, under attack by something so tiny it could only be discerned by the damage it did. People around the world—doctors, veterinarians—send him tissue samples, Calisher explained, asking him to grow a virus from the stuff and identify it. Okay. That sort of thing has been his life’s work, especially with regard to hantaviruses in rodents. And then came this little excursion into bats.
We repaired to his office, now almost empty as he eased into retirement, except for a desk, two chairs, a computer, and some boxes. He tilted back in his chair, set his boots on the desk, and began to talk: arboviruses, the CDC, hantaviruses in rodents, La Crosse virus, mosquitoes, and a congenial group called the Rocky Mountain Virology Club. He ranged widely but, knowing my interest, circled back to a consequential chat he’d had with a colleague about six years earlier, soon after news broke that SARS, the new killer coronavirus, had been traced to a Chinese bat. The colleague was Kathryn V. Holmes, an expert on coronaviruses and their molecular structure, at the University of Colorado Health Sciences Center near Denver, just down the highway from Fort Collins. Charlie told me the story in his own vivid way, complete with dialogue:
“We oughta write a review paper about bats and their viruses,” he said to Kay Holmes. “This bat coronavirus is really interesting.”
She seemed intrigued but a little dubious. “What would we include?”
“Well, this and that, something else,” Charlie said vaguely. The idea was still taking shape. “Maybe immunology.”
“What do we know about immunology?”
Charlie: “I don’t know shit about immunology. Let’s ask Tony.”
Tony Schountz, another professional friend, is an immunologist at the University of Northern Colorado, in Greeley, who does research on responses to hantaviruses in humans and mice. At that time Schountz, like Calisher, had never studied chiropterans. But he is a burly young guy, a former athlete, who had played college baseball as a catcher.
“Tony, what do you know about bats?”
Schountz thought Charlie meant Louisville Sluggers. “They’re made of ash.”
“Hello, Tony? I’m talkin’ about bats.” Wing-flapping gesture. As distinct from: DiMaggio gesture.
“Oh. Uh, nothing.”
“You ever read anything about the immunology of bats?”
“No.”
“Have you ever seen any papers on the immunology of bats?”
“No.”
Neither had Charlie—nothing beyond the level of finding antibodies that confirmed infection. Nobody seemed to have addressed the deeper question of how chiropteran immune systems respond. “So I said to Kay, ‘Let’s write a review paper,’ ” Charlie told me. “Tony said, ‘Are you crazy? We don’t know anything!’ ”
“Well, she doesn’t know anything, you don’t know anything, and I don’t know anything. This is great. We don’t have any biases.”
“Biases?” said Schountz. “We don’t h
ave any information!”
“I said, ‘Tony, that shouldn’t hold us back.’ ”
Thus the workings of science. But Calisher and his two pals didn’t plan to flaunt their ignorance. If we don’t know anything in this or that area, he proposed, we’ll just get somebody who does. They enlisted James E. Childs, an epidemiologist and rabies expert at the Yale School of Medicine (and an old friend of Charlie’s from CDC days), and Hume Field, who by now was turning up everywhere. This five-member team, with their patchwork of expertise and their sublime lack of biases, then wrote a long, wide-ranging paper. Several journal editors voiced interest but wanted the manuscript cut; Charlie refused. It appeared finally, intact, in a more expansive journal, under the title “Bats: Important Reservoir Hosts of Emerging Viruses.” It was a review, as Charlie had envisioned, meaning that the five authors made no claim of presenting original research; they simply summarized what had previously been done, gathered disparate results together (including unpublished data contributed by others), and sought to highlight some broader patterns. That much, it turned out, was a timely service. The paper offered a rich compendium of facts and ideas—and where facts were scarce, directive questions. Other disease scientists noticed. “All of a sudden,” Charlie told me, “the phone’s ringing off the hook.” They met hundreds of requests for reprints, maybe thousands, sending their “Bats: Important Reservoir Hosts” to colleagues worldwide in the form of a PDF. Everybody wanted to know—everybody in that professional universe anyway—about these new viruses and their chiropteran hideouts. Yes, what is the deal with bats?
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