Spillover

by David Quammen

  The Slammer at USAMRIID is a medical containment suite, designed for care of a person infected with any dangerous pathogen and—equally—for protecting against the spread of that infection to others. It consists of two hospital-style rooms set behind more pressure-sealed doors and another chemical shower. Earlier on the day of our conversation, having gotten me clearance for a tour of USAMRIID, Warfield had shown me through the Slammer, explaining its features with a trace of mordant pride. On the outside, a wide main door is labeled: CONTAINMENT ROOM. AUTHORIZED PERSONNEL ONLY. That’s door number 537 within USAMRIID’s labyrinthine corridors. It’s the door through which a new patient enters the suite and, if things go well, through which the same patient eventually walks out. If things don’t go well, the patient exits under other circumstances, not walking and not via door 537. All other human traffic—the flow of medical caregivers and faithful, intrepid friends—must pass through a smaller door into a change room, where piles of scrub suits sit folded and ready on shelves, and then through a pressurized steel door into an airlock shower. On the other side of the shower stall is another steel door. The two pressurized steel doors are never both open at once. So long as the patient shows no signs of infection, approved visitors are admitted to the Slammer wearing scrubs, gowns, masks, and gloves. If the patient proves to be infected, the suite becomes an active BSL-4 zone, in which doctors and nursing staff (no visitors now) must wear full blue suits. In that situation, the medical people shower thoroughly on the way out, leaving their scrub clothing behind in a bag to be autoclaved.

  Warfield led me. We could pass through the shower stall in street clothes because the containment suite was unoccupied. When she slammed the first steel door behind us, triggering pressurization, I heard a voosh and felt the change in my ears. She said: “There’s why it’s called the Slammer.”

  She had entered the suite around noon on February 12, 2004, the day following her accident, after having drawn up a will and an advance directive (stipulating end-of-life medical decisions) with help from an Army lawyer. Her husband was in Texas for advanced military training and she had apprised him of the situation by phone. In fact, she had stayed on the phone with him much of the previous night, helped through the hours of terror and dread by his long-distance support. At some point she told him: “If I get sick, please please give me a lot of morphine. I’ve seen this disease”—she had watched it kill monkeys in the lab, though never a human—“and I know it hurts.” On the first weekend, he managed to fly up from Texas and they spent Valentine’s Day in the suite holding hands through his latex gloves. There was no kissing through his mask.

  The incubation period for Ebola virus disease, as I’ve mentioned, is reckoned to be at least two days; it can be longer than three weeks. Individual case histories differ, of course, but at that time twenty-one days seemed to be the outer limit. Expert opinion held that, if an exposed person hasn’t shown the disease within that length of time, she wouldn’t. Kelly Warfield was therefore sentenced to twenty-one days in the Slammer. “It was like prison,” she told me. Then she amended her statement: “It’s like prison and you’re gonna die.”

  Another difference from prison is that there were more blood tests. Each morning her friend Diane Negley, who happened to be a certified phlebotomist and who knew enough about Ebola to be cognizant of the risk to herself, tapped a vein and took away some of Warfield’s blood. In exchange, she brought a donut and a latte. Negley’s morning visit was the highlight of Warfield’s day. During the first week or so, Negley took fifty milliliters of blood daily, a sizable volume (more than three tablespoons) that allowed for multiple tests plus a bit extra to put in frozen storage. One test, using the PCR (polymerase chain reaction) technique that’s familiar to all molecular biologists, looked for sections of Ebola RNA (the virus’s genetic molecule, equivalent to human DNA) in her blood. That test, which can ring a loud alarm but is sometimes unreliable, delivering a false positive, was routinely performed twice on each sample. Another test screened for interferon, the presence of which might signal a viral infection of any sort. Still another test targeted changes in blood coagulation, for an early alert in case of disseminated intravascular coagulation, the catastrophic clotting phenomenon that makes blood ooze out where it shouldn’t. Warfield encouraged the medical people to take all the blood they desired. She recalled telling them: “If I die, I want you to learn everything you can about me”—everything they could about Ebola virus disease, she meant. “Store every sample. Analyze everything you can. Please please take something away from this if I die. I want you to learn.” She told her family the same: If the worst happens, let them autopsy me. Let them salvage all possible information.

  If she did die, Warfield knew, her body wouldn’t come out of the Slammer through door 537. After autopsy, it would come through the autoclave chute, a sterilizing cooker, which would leave nothing her loved ones would want to see in an open coffin.

  All her test results during the first week were normal and reassuring—with a single exception. The second PCR test from one day’s sample came back positive. It said she had Ebola virus in her blood.

  It was wrong. The provisional result gave Warfield a fright but that mistake was soon corrected by further testing. Woops, no, sorry. Never mind.

  Another kerfuffle arose when USAMRIID’s leadership realized that Warfield suffered rheumatoid arthritis, the medications for which might have suppressed her immune system. “That became this huge controversy,” she told me. Certain honchos of the institute’s top leadership acted surprised and angry, although the condition was clearly on file in her medical records. “They had all these teleconferences with all these experts. Everybody wanted to know why someone that was immunocompromised was working in the BSL-4 suites.” There was in fact no evidence that her immune system wasn’t working fine. The commander of USAMRIID never made a personal visit to see her in the Slammer, not even through the glass, but he sent her an email announcing that he was suspending her access to BSL-4 labs and impounding her badge. It was a “slap in the face,” added onto her other miseries and worries, Warfield said.

  After more than two weeks of vampiric blood draws and reassuring tests, Warfield began feeling guardedly confident she wouldn’t die of Ebola. She was weak and weary, her veins were weary too, so she asked that the blood sampling be reduced to a daily minimum. She got another unsettling jolt one evening as she undressed, discovering red spots on her arm and wondering whether they might herald the start of Ebola’s characteristic rash. She had seen similar spots on lab-infected monkeys. That night she lay awake, obsessing about the spots, but they turned out to be nothing. She had Ambien to help her sleep. She had a stationary bike in case she wanted exercise. She had TV and Internet and a phone. As the weeks passed, the terrifying element of her situation faded slowly beneath the good news and the tedium.

  She stayed sane with help from her mother and a few close friends (who could visit her often), her husband (who couldn’t), her father (who remained off the visitor list so he could look after her son, in case everyone else got infected and quarantined and then died), and a certain amount of nervous laughter. Her son, whose name is Christian, was just three at the time and barred by age regulations from entering USAMRIID. Warfield judged he was too young, in any case, to be burdened with knowing exactly what was going on; she and her husband explained to Christian simply that mom would be absent for three weeks doing “special work.” She was given a video linkup, a sort of Slammer Cam, through which she could see and talk with her loved ones on the outside. Hi, it’s me, Kelly, live from Ebolaville, how was your day? Diane Negley, besides supplying the morning donut and coffee, heroically smuggled in one beer every Friday night. Food was a problem at first, there being no cafeteria at USAMRIID, until the Army realized it had funds that could be spent on supplying a patient in the Slammer with carryout. After that, Warfield had her choice each evening among Frederick’s best: Chinese, Mexican, pizza. And she could share with her visiting
friends, such as Negley, who would sit in the blind spot beneath the security camera, flip up her face shield, and eat. These high-carb consolations led Warfield and her pals to invent a game: “Ebola Makes You . . .” and then fill in the blank. Ebola makes you fat. Ebola makes you silly. Ebola makes you diabetic from too much chocolate ice cream. Ebola makes you appreciate little joys and smiles in the moment.

  On the morning of March 3, 2004, door 537 opened and Kelly Warfield walked out of the Slammer. Her mother and (by special exemption) Christian were in the waiting room down the corridor. She took her son home. That afternoon she returned to USAMRIID, where her friends and colleagues threw her a coming-out party with food, testimonials, and balloons. Several months later, after a period of suspended access, a battery of tests on her immune system, a somewhat humiliating regimen of retraining and supervision, and a bit of persistent struggle, she regained her clearance for the BSL-4 suites. She could return to tickling the tail of the dragon that might have killed her.

  Did you ever consider not going back to Ebola? I asked.

  “No,” she said.

  Why do you love this work so much?

  “I don’t know,” she said, and began to ruminate. “I mean, why Ebola? It only kills maybe a couple hundred people a year.” That is, it hasn’t been a disease of massive global significance and, notwithstanding the lurid scenarios that some people evoke, it’s unlikely ever to become one. But she could cite its attractions in scientific terms. She took deep interest, for instance, in the fact that such a simple organism can be so potently lethal. It contains only a tiny genome, enough to construct just ten proteins, which account for the entire structure, function, and self-replicating capacity of the thing. (A herpesvirus, by contrast, carries about ten times more genetic complexity.) Despite the minuscule genome, Ebola virus is ferocious. It can kill a person in seven days. “How can something that is so small and so simple just be so darn dangerous?” Warfield posed the question and I waited. “That’s just really fascinating to me.”

  Her son Christian, grown to a handsome first-grader, at this point arrived home from school. Kelly Warfield had given me most of her day and now there was time for just one more question. Although she is a molecular biologist, not an ecologist, I mentioned those two unsolved mysteries of Ebola’s life in the wild: the reservoir host and the spillover mechanism.

  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.

  19

  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 for 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.

  20

  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 studied the effects of another kind of virus (SIV, of which much more below) 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.