Ebola: The Natural and Human History of a Deadly Virus

by David Quammen

  Much of her effort went into the VLP research, though she also helped on other projects within her boss’s lab. One involved testing a form of laboratory-created antibodies that might serve as a treatment against Ebola virus disease. These antibodies, developed by a private company in collaboration with USAMRIID, were designed to thwart the virus by tangling with a cellular protein involved in viral replication, not with the virus itself. It was a clever idea. Warfield again used mice as her test animals; she now had years of experience at handling and injecting them. For the experiment she infected fifty or sixty mice with Ebola virus and then, during the following days, gave them the experimental antibody treatment. Would they live, would they die? The mice were kept in clear plastic cages, like tall-sided pans, ten mice to a pan. Methodical procedures and constant attention are crucial to BSL-4 work, as Warfield well knew. Her methodical procedures for this experiment included filling a syringe full of antibody solution, enough for ten doses, and then injecting the ten mice from each pan with the same syringe, the same needle. It wasn’t as though cross-infection was a concern, since they had already been dosed with the same batch of Ebola. Dosing multiple mice with a single syringe saved time, and time in a BSL-4 lab adds up toward stress and increased risk, because the physical circumstances are so difficult.

  Picture those circumstances for Kelly Warfield. Customarily she worked in the BSL-4 suite known as AA-5, off a cinderblock corridor in the most secure wing of USAMRIID, behind three pressure-sealed doors and a Plexiglas window. She wore a blue vinyl protective suit (she and her colleagues simply called them “blue suits,” not spacesuits or hazmats) with a fully enclosed hood, a clear face shield, and a ventilation hookup. Attached to her hookup was a yellow hose, coiling down from the ceiling to bring filtered air. She wore rubber boots and two pairs of gloves—latex gloves beneath heavier canners gloves, sealed to her suit at the wrists with electrical tape. Even with canners gloves over latex, her hands were the most vulnerable part of her body; they couldn’t be protected with vinyl because they had to be delicately dexterous. Her workbench was a stainless steel cart, like a hospital cart, easy to clean, easy to move. If you didn’t love the work, you wouldn’t put yourself in this place.

  She was alone in AA-5, under exactly those circumstances, at five thirty on the evening of February 11, 2004. She had come late to the day’s tasks for the Ebola experiment because earlier hours had been filled with other demands. One pan of mice sat on her cart, along with a plastic beaker, a clipboard, and not much else in the way of materials and tools. It was the last pan of mice for the day. She filled a syringe and carefully injected nine mice, one after another—gripping each animal by the skin behind its neck, turning it belly up, inserting the needle into its abdomen deftly, quickly, adding no more discomfort than necessary to the life of each doomed and Ebola-ridden mouse. After each injection, she placed that mouse in the beaker, to keep the finished group apart from the others. One mouse to go. Maybe she was a little tired. Accidents happen. It was this very last mouse that caused the trouble. Just after being injected, it kicked away the needle, deflecting the point into the base of Kelly Warfield’s left thumb.

  The wound, if there was a wound, seemed to be only a very light graze. “At first, I didn’t think that the needle went through the gloves,” she told me. “It didn’t hurt. Nothing hurt.” Remaining calm by an act of discipline, she set the mouse back in its pan, put the syringe away, and then squeezed her hand. She could see blood emerging under the layers of glove. “So I knew I had stuck myself.”

  We were seated at her dinette table, on a mild September afternoon, as she talked me through the events of that February day. The house, which she shared with her Army-physician husband and her young son, was light and cheery with a lived-in feel; there were pieces of kid art on the refrigerator, a few toys lying around, a large green backyard, two half-poodle dogs, and a sign on the kitchen wall commanding: DO NOT ENTER WITHOUT WEARING VENTILATED SUIT. Today she was dressed in a red jacket and pearl earrings, not in blue vinyl.

  She recalled her mind racing forward, from an immediate “Oh my God, I’ve done it” reaction to a sober consideration of just what she had done. She had not injected herself with live Ebola virus—or at least, not much. The syringe didn’t carry Ebola virus; it carried antibodies, which would be harmless to anyone. But the needle had gone into ten Ebola-infected mice before going into her. If its point had picked up any particles of Ebola and brought them along, then she might have received a tiny dose. And she knew that a tiny dose could be enough. Quickly she unhooked her yellow hose and exited the BSL-4 suite, by way of the first of the pressurized doors, into an airlock space equipped with a chemical shower. There she showered out, dosing her blue-suit exterior with a virus-killing solution.

  Then she pushed through the second door, to a locker-room area known as the Gray Side. She shed the boots, peeled off the blue suit and the gloves as fast as she could, leaving her clad only in medical scrubs. She used a wall phone to call two close friends, one of whom was Diane Negley, the BSL-4 suite supervisor. It was now suppertime or later, and Negley didn’t answer at home, so Warfield left a chilling, desperate message on Negley’s machine, the gist of which was: I’ve had an accident, stuck myself, please come back to work. The other friend, a co-worker named Lisa Hensley, who hadn’t yet left the building, answered her call and said: “Start scrubbing. I’m on my way down.” Warfield began scrubbing her hands with Betadine, rinsing with water and saline solution, scrubbing again. In her fervor she splashed water all over the floor. Hensley arrived quickly, joined her in the Gray Side, and started making calls to alert other people, including those in the Medical Division who handled accidents, while Warfield continued the Betadine scrub. After five or ten minutes, feeling she had done what she could on the wound site, Warfield stripped out of her medical scrubs, took a soap-and-water shower, and dressed. Hensley did likewise. But when they tried to exit the Gray Side, that pressure-sealed door wouldn’t open. Its electronic lock didn’t respond to their badges. Warfield, full of adrenaline, scared, with no luxury of being patient, busted open the door on manual override and alarms started ringing in other parts of the building.

  Word had spread fast through the institute and, by now, a small crowd had gathered in the corridor. Warfield passed amid their stares and their questions, headed for the Medical Division. There she was ushered into a small room, questioned about her accident by the doctor on duty, a civilian woman, and given a “physical exam,” through the whole course of which the doctor never touched her. “It was like she was afraid that I already had Ebola,” Warfield recalled. The incubation period for Ebola virus is measured in days, not hours or minutes. It takes at least two days and usually more than a week for the virus to establish itself, replicate abundantly, and make a person symptomatic or infectious. But the civilian doctor didn’t seem to know that, or to care. “She acted like I was a leper already.” That doctor went off to confer with others, after which the head of the Medical Division took Warfield into his office, sat her down, and gently told her the recommended next step. They wanted to put her in the Slammer.

  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 caregiv
ers 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 st
ruggle, 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 hadn’t been a disease of massive global significance, not at the time of this conversation, in 2008 (although, amid the frightful events of 2014, it has certainly captured global attention, while increasing its death toll and breadth of impact alarmingly). Apart from the numbers, 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.