Yes, very intriguing also, she agreed. “It pops up and kills a bunch of people, and before you can get there and figure anything out, it’s gone.”
It disappears back into the Congo forest, I said.
“It disappears,” she agreed. “Yeah. Where did it come from and where did it go?” But that was out of her area.
12
THINK OF A BSL-4 laboratory—not necessarily AA-5 at USAMRIID but any among a handful around the world in which this virus is studied. Think of the proximity, the orderliness, and the certitude. Ebola virus is in these mice, replicating, flooding their bloodstreams. Ebola virus is in that tube, frozen solid. Ebola virus is in the Petri dish, forming plaques among human cells. Ebola virus is in the syringe; beware its needle. Now think of a forest in northeastern Gabon, just west of the upper Ivindo River. Ebola virus is everywhere and nowhere. Ebola virus is present but unaccounted for. Ebola virus is near, probably, but no one can tell you which insect or mammal or bird or plant is its secret repository. Ebola virus is not in your habitat. You are in its.
That’s how Mike Fay and I felt as we hiked through the Minkébé forest in July 2000. Six days after my helicopter fly-in we left the inselbergs area, trudging southwest on Fay’s compass line through a jungle of great trees, thorny vines interwoven into torturous thickets, small streams and ponds, low ridges between the stream drainages, mud-bordered swamps dense with thorny vegetation, fallen fruits as big as bocce balls, driver ants crossing our path, groups of monkeys overhead, forest elephants in abundance, leopards, almost no signs of human visitation, and roughly a trillion cheeping frogs. The reservoir host of Ebola virus was there too, presumably, but we couldn’t have recognized it as that if we’d looked it in the face. We could only take sensible precautions.
On the eleventh day of walking, one of Fay’s forest crewmen spotted a crested mona monkey on the forest floor, a youngster, alive but near death, with blood dripping from its nostrils. Possibly it had missed its grip in a high tree and suffered a fatal fall. Or … maybe it was infected with something, such as Ebola, and came down to die. Under standing instructions from Fay, the crewman didn’t touch it. Fay’s crew of hardworking Bantus and Pygmies always hungered after wild meat for the evening pot, but he forbade hunting on conservation grounds—and during this stretch through Minkébé he had commanded his cook even more sternly: Do not feed us anything found dead on the ground. That night we ate another brownish stew, concocted from the usual freeze-dried meats and canned sauces, served over instant mashed potatoes. The dying monkey, I fervently hoped, had been left behind.
One night later, at the campfire after dinner, Fay helped me tease some direct testimony from Sophiano Etouck, the shier of the two survivors from Mayibout 2. I had heard the whole story—including the part about Sophiano’s personal losses—from the voluble Thony M’Both, but Sophiano himself, burly, diffident, had never spoken up. Now finally he did. The sentences were diced cruelly by his stutter, which sometimes brought him to what seemed an impassable halt; but Sophiano pushed on, and between blockages his words came quickly.
He had been traveling to one of the gold camps. Farther upriver. And stopped in Mayibout 2 to stay with family. That night one of his nieces said she was feeling bad. Malaria, everyone thought. A routine thing. The next morning, it got worse. Then other people too. They vomited, they had diarrhea. Started dying. I lost six, Sophiano said. Thony had gotten the number right but was a little confused about the identities. An uncle, a brother, a widowed sister-in-law. Her three daughters. The men in white suits, they came to take charge. One of them, a Zairian, had seen the disease before. At Kikwit. Twenty doctors had died there at Kikwit, the Zairian told us. They told us, this thing is very infectious. If a fly lands on you after having touched one of the corpses, they said, you will die. But I held one of my nieces in my arms. She had a tube in her wrist, an IV drip. It got clogged, backed up. Her hand swelled. And then with a pop her blood sprayed all over my chest, Sophiano said. But I didn’t get sick. You’ve got to take the remedy, the doctors told me. You’ve got to stay here twenty-one days under quarantine. I thought, the hell with that. I didn’t take the remedy. After my family people had been buried, I left Mayibout 2. I went to Libreville and stayed with another sister, hiding, Sophiano confessed. Because I was afraid the doctors would hassle me, he said.
This was our last evening in the forest before a resupply rendezvous four or five miles onward, at a point where Fay’s preplotted line of march crossed a road. That road led eastward to Makokou. Some of Fay’s crew would leave him there. They were exhausted, spent, fed up. Others would stay with him because, though also exhausted, they needed the work badly, or because it was better than gold mining, or because those reasons supplemented another: the sheer fascination of being involved with an enterprise so sublimely crazed and challenging. Another half year of hard walking across forests and swamps lay between them and Fay’s end point, the Atlantic Ocean.
Sophiano would stay. He had been through worse.
13
THE IDENTITY OF Ebola’s reservoir host (or hosts) remains unknown, as of this writing, although suspects have been implicated. Several different groups of researchers have explored the question. The most authoritative, most advantageously placed, and most persistent of them is the team led by Eric M. Leroy, of CIRMF, in Franceville, Gabon. As mentioned earlier, Leroy was one of the visiting doctors dressed in mystifying white suits who took part in the response effort at Mayibout 2. Although he and his colleagues may not have saved many (or any, as remembered by Thony M’Both) of the Mayibout patients from death, that outbreak was transformative for Leroy himself. He trained as an immunologist as well as a veterinarian and a virologist, and until 1996 he studied the effects of another kind of virus on the immune systems of mandrills. Mandrills are large, baboonlike monkeys with red noses, puffy blue facial ridges, and contorted expressions, all of which give them the look of angry, dark clowns. Leroy was also curious about the immune physiology of bats. Then came Mayibout 2 and Ebola.
“It is a little bit like a fate,” Leroy told me when I visited him in Franceville.
Back at CIRMF after Mayibout 2, he explored Ebola further in his lab. He and a colleague, like him an immunologist, investigated some molecular signals in blood specimens taken during the outbreak. They found evidence suggesting that the medical outcome for an individual patient—to survive and recover, or to die—might be related not to the size of the infectious dose of Ebola virus but to whether the patient’s blood cells produced antibodies promptly in response to infection. If they didn’t, why not? Was it because the virus itself somehow quickly decommissioned their immune systems, interrupting the normal sequence of molecular interactions involved in antibody production? Does the virus kill people (as is now widely supposed) by creating immune dysfunction before overwhelming them with viral replication, which then inflicts further devastating effects? Leroy and his immunologist colleague, with a group of additional coauthors, published this study in 1999, after which he became interested in other dimensions of Ebola: its ecology and its evolutionary history.
The ecology of Ebola virus encompasses the reservoir question: Where does it hide between outbreaks? Another ecological matter is spillover: By what route, and under what circumstances, does the virus pass from its reservoir into other animals, such as apes and humans? To ask those questions is one thing; to get data that might help answer them is more tricky. How does a scientist study the ecology of such an elusive pathogen? Leroy and his team went into the forest, near locations where Ebola-infected gorilla or chimp carcasses had recently been found, and began trapping animals wholesale. They were groping. Ebola might abide in one of these creatures—but which one?
In the course of several expeditions between 2001 and 2003, into Ebola-stricken areas of Gabon and the Republic of the Congo, Leroy’s group caught, killed, dissected, and took samples of blood and internal organs from more than a thousand animals. Their harvest included 222 birds of v
arious species, 129 small terrestrial mammals (shrews and rodents), and 679 bats. Back at the lab in Franceville, they tested the samples for traces of Ebola using two different methods. One method was designed to detect Ebola-specific antibodies, which would be present in animals that had responded to infection. The other method used PCR (as it had been used on Kelly Warfield) to screen for fragments of Ebola’s genetic material. Having looked so concertedly at the bat fauna, which accounted for two-thirds of his total collections, Leroy found something: evidence of Ebola virus infection in bats of three species.
These three were all fruit bats, relatively big and ponderous. One of them, the hammer-headed bat (Hypsignathus monstrosus), is the largest bat in Africa, as big as a crow. People hunt it for food. But in this case the evidence linking bats and virus, though significant, wasn’t definitive. Sixteen bats (including four hammer-headed) had antibodies. Thirteen bats (again including some hammer-headed) had bits of the genome of Ebola virus, detectable by PCR. That amounted to twenty-nine individuals, representing a small fraction of the entire sample. And the results among even those twenty-nine seemed ambiguous, in that no individual bat tested positive by both methods. The sixteen bats with antibodies contained no Ebola RNA, and vice versa. Furthermore, Leroy and his team did not find live Ebola virus in a single bat—nor in any of the other animals they opened.
Ambiguous or not, these results seemed dramatic when they appeared in a paper by Leroy and his colleagues in late 2005. It was a brief communication, barely more than a page, but published by Nature, one of the world’s most august scientific journals. The headline ran: FRUIT BATS AS RESERVOIRS OF EBOLA VIRUS. The text itself, more carefully tentative, said that bats of three species “may be acting as a reservoir” of the virus. Some experts reacted as though the question were now virtually settled, others reserved judgment. “The only thing missing to be sure that bats are the reservoir,” Leroy told me, during our conversation ten months later, “is virus isolation. Live virus from bats.” That was 2006. It still hasn’t happened, so far as the world knows, though not for lack of effort on his part. “We continue to catch bats—to try to isolate the virus from their organs,” he said.
But the reservoir question, Leroy emphasized, was only one aspect of Ebola that engaged him. Using the methods of molecular genetics, he was also studying its phylogeny—the ancestry and evolutionary history of the whole filovirus lineage, including Marburg virus and the various ebolaviruses. He wanted to learn too about the natural cycle of the virus, how it replicates within its reservoir (or reservoirs) and maintains itself in those populations. Finally, knowing something about the natural cycle would help in discovering how the virus is transmitted to humans: the spillover moment. Does that transmission somehow occur directly (for instance, by people eating bats), or through an intermediate host? “We don’t know if there’s direct transmission from bats to humans,” he said. “We only know there is direct transmission from dead great apes to humans.” Understanding the dynamics of transmission—including seasonal factors, the geographical pattern of outbreaks, and the circumstances that bring reservoir animals or their droppings into contact with apes or humans—might give public health authorities a chance to predict and even prevent some outbreaks. But there exists a grim circularity: Gathering more data requires more outbreaks.
Ebola is difficult to study, Leroy explained, because of the character of the virus. It strikes rarely, it progresses quickly through the course of infection, it kills or it doesn’t kill within just a few days, it affects only dozens or hundreds of people in each outbreak, and those people generally live in remote areas (again, he was right on both points until 2014), far from research hospitals and medical institutes—far even from his institute, CIRMF. (It takes about two days to travel, by road and river, from Franceville to Mayibout 2.) Then the outbreak exhausts itself locally, coming to a dead end, or is successfully stanched by intervention. The virus disappears like a band of jungle guerrillas. “There is nothing to do,” Leroy said, expressing the momentary perplexity of an otherwise patient man. He meant, nothing to do except keep trying, keep working, keep sampling from the forest, keep responding to outbreaks as they occur. No one can predict when and where Ebola virus will next spill. “The virus seems to decide for itself.”
14
THE GEOGRAPHICAL PATTERN of Ebola outbreaks among humans is controversial. Everyone knows what that pattern looks like but experts dispute what it means. The dispute involves Ebola virus in particular, the one among those five ebolaviruses that has emerged most frequently, in multiple locations across Africa, and therefore cries most loudly for explanation. From its first known appearance to the present, from Yambuku (1976) to Tandala (1977) to the upper Ivindo River gold camps (1994) to Kikwit (1995) to Mayibout 2 (1996) to Booué (later 1996) to the northern border region between Gabon and the Republic of the Congo (2001–2002) to the Mbomo area (2002–2003) to its recurrence at Mbomo (2005), and then to its two appearances near the Kasai River in what’s now the Democratic Republic of the Congo (2007–2009), and most recently to Guinea, Sierra Leone, Liberia, and Nigeria (2013–2014), Ebola virus has seemingly hopscotched its way around Central and West Africa. What’s going on? Is that pattern random or does it have causes? If it has causes, what are they?
Two schools of thought have arisen. I think of them as the wave school and the particle school—my little parody of the classic wave-or-particle conundrum about the nature of light. Back in the seventeenth century, as your keen memory for high-school physics will tell you, Christiaan Huygens proposed that light consists of waves, whereas Isaac Newton argued that light is particulate. They each had some experimental grounds for believing as they did. It took quantum mechanics, more than two centuries later, to explain that wave-versus-particle is not a resolvable dichotomy but an ineffable duality, or at least an artifact of the limitations of different modes of observing.
The particle view of Ebola sees it as a relatively old and ubiquitous virus in Central African forests, and each human outbreak as an independent event, primarily explicable by an immediate cause. For instance: Somebody scavenges an infected chimpanzee carcass; the carcass is infected because the chimp itself scavenged a piece of fruit previously gnawed by a reservoir host. The subsequent outbreak among humans results from a local, accidental event, each outbreak therefore representing a particle, discrete from others. Eric Leroy is the leading proponent of this view. “I think the virus is present all the time, within reservoir species,” he told me. “And sometimes there is transmission from reservoir species to other species.”
The wave view suggests that Ebola has not been present throughout Central Africa for a long time—that, on the contrary, it’s a rather new virus, descended from some viral ancestor, perhaps in the Yambuku area, and come lately to other sites where it has emerged. The local outbreaks are not independent events, but connected as part of a wave phenomenon. The virus has been expanding its range within recent decades, infecting new populations of reservoir in new places. Each outbreak, by this view, represents a local event primarily explicable by a larger cause—the arrival of the wave. The main proponent of the wave idea is Peter D. Walsh, an American ecologist who has worked often in Central Africa and specializes in mathematical theory about ecological facts.
“I think it’s spreading from host to host in a reservoir host,” Walsh said, when I asked him to explain where the virus was traveling and how. This was another conversation in Libreville, a teeming Gabonese city with pockets of quietude, through which all Ebola researchers eventually pass. “Probably a reservoir host that’s got large population sizes and doesn’t move very much. At least, it doesn’t transmit the virus very far.” Walsh didn’t claim to know the identity of that reservoir, but it had to be some animal that’s abundant and relatively sedentary. A rodent? A small bird? A nonmigrating bat?
The evidence on each side of this dichotomy is varied and intriguing, though inconclusive. One form of that evidence is the genetic differenc
es among strains of Ebola virus as they have been found, or left traces of themselves, in human victims, gorillas, and other animals sampled at different times and places. Ebola virus in general seems to mutate at a rate comparable to other RNA viruses (which means relatively quickly), and the amount of variation detectable between one strain of Ebola virus and another can be a very important clue about their origins in space and time. Peter Walsh, working with two coauthors on a paper published in 2005, combined such genetic data with geographical analysis to suggest that all known variants of Ebola virus descended from an ancestor closely resembling the Yambuku virus of 1976.
Walsh’s collaborators were Leslie Real, a highly respected disease ecologist and theoretician at Emory University, and a bright younger colleague named Roman Biek. Together they presented maps, graphs, and family trees illustrating strong correlations among three kinds of distance: distance in miles from Yambuku, distance in time from that 1976 event, and distance in genetic differences from the Yambuku-like common ancestor. “Taken together, our results clearly point to the conclusion that [Ebola virus] has gradually spread across central Africa from an origin near Yambuku in the mid-1970s,” they wrote.19 Their headline, stating the thesis plainly, was WAVE-LIKE SPREAD OF EBOLA ZAIRE. It may or may not be a new pathogen—at least, new in these places. (Other evidence, published more recently, suggests that filoviruses may be millions of years old.) But maybe something happened, and happened rather recently, to reshape the virus and unleash it upon humans and apes. “Under this scenario, the distinct phylogenetic tree structure, the strong correlation between outbreak date and distance from Yambuku, and the correlation between genetic and geographic distances can be interpreted as the outcome of a consistently moving wave of [Ebola virus] infection.” One consequence of the moving wave, they argued, is massive mortality among the apes. Some regional populations have been virtually exterminated—such as the gorillas of the Minkébé forest, of the Lossi Gorilla Sanctuary, of the area around Moba Bai—because Ebola hit them like a tsunami.
Ebola: The Natural and Human History of a Deadly Virus Page 8