Spillover

by David Quammen

  The English accident occurred at Britain’s Microbiological Research Establishment, a discreetly expert institution within a high-security government compound known as Porton Down, not far from Stonehenge in the rolling green countryside southwest of London. Think of Los Alamos, but tucked into the boonies of pastoral England instead of the mountains of New Mexico, and with bacteria and viruses in place of uranium and plutonium as the strategic materials of interest. In its early years, beginning in 1916, Porton Down was an experiment station for the development of chemical weapons such as mustard gas; during World War II, its scientists worked also on biological weapons derived from anthrax and botulin bacteria. But eventually, at Porton Down as at USAMRIID, with changing political circumstances and government scruples, the emphasis shifted to defense—that is, research on countermeasures against biological and chemical weapons. That work involved high-containment facilities and techniques for studying dangerous new viruses, and therefore qualified Porton Down to offer assistance in 1976, when WHO assembled a field team to investigate a mysterious disease outbreak in southwestern Sudan. Deep-frozen blood samples from desperately ill Sudanese patients arrived for analysis—at about the same time, during that fretful autumn, as blood samples from Yambuku went to the CDC. The field people were asking the laboratory people to help answer a question: What is this thing? It hadn’t yet been given a name.

  One of the lab people at Porton Down was Geoffrey S. Platt. On November 5, 1976, in the course of an experiment, Platt filled a syringe with homogenized liver from a guinea pig that had been infected with the Sudanese virus. Presumably he intended to inject that fluid into another test animal. Something went amiss, and instead he jabbed himself in the thumb.

  Platt didn’t know exactly what pathogen he had just exposed himself to, but he knew it wasn’t good. The fatality rate from this unidentified virus, as he must have been aware, was upwards of 50 percent. Immediately he peeled off his medical glove, plunged his thumb into a hypochlorite solution (bleach, which kills virus) and tried to squeeze out a drop or two of blood. None came. He couldn’t even see a puncture. That was a good sign if it meant there was no puncture, a bad sign if it meant a little hole sealed tight. The tininess of Platt’s wound, in light of subsequent events, testifies that even a minuscule dose of an ebolavirus is enough to cause infection, at least if that dose gets directly into a person’s bloodstream. Not every pathogen is so potent. Some require a more sizable foothold. Ebolaviruses have force but not reach. You can’t catch one by breathing shared air, but if a smidgen of the virus gets through a break in your skin (and there are always tiny breaks), God help you. In the terms used by the scientists: It’s not very contagious but it’s highly infectious. Six days after the needle prick, Geoffrey Platt got sick.

  At the start he merely felt nauseous and exhausted, with abdominal pain. Given the circumstances, though, his malaise was taken very seriously. He was admitted to a special unit for infectious diseases at a hospital near London and, within that unit, put into a plastic-walled isolator tent under negative air pressure. The historical records don’t mention it but you can be sure his nurses and doctors wore masks. He was given injections of interferon, to help stimulate his immune system, and blood serum (flown up from Africa) that had been drawn from a recovered Ebola patient to supply some borrowed antibodies. On the fourth day, Platt’s temperature spiked and he vomited. This suggested the virus was thriving. For the next three days, his crisis period, he suffered more vomiting, plus diarrhea, and a spreading rash; his urine output was low; and a fungal growth in his throat hinted at immune failure. All these were gloomy signs. Meanwhile he was given more serum. Maybe it helped.

  By the eighth day, Platt’s vomiting and diarrhea had ended. Two days later, the rash began to fade and the fungus was under control. He had been lucky, perhaps genetically, as well as privileged to receive optimal medical care. The virus disappeared from his blood, from his urine, and from his feces (though it lingered awhile in his semen; apparently he promised doctors that he wouldn’t make that a risk issue for anyone else). He was taken out of the isolator. Eventually he went home. He had lost weight, and during the long, slow convalescence much of his hair fell out. But like the Swiss woman, he survived.

  The Russian researcher, in 1996, wasn’t so lucky. Her name, as given in one Russian news account (but unspoken in the western medical literature), was Nadezhda Alekseevna Makovetskaya. Employed at a virological institute under the Ministry of Defense, she had been working on an experimental therapy against Ebola virus disease, derived from the blood serum of horses. Horses aren’t susceptible to Ebola—not like they are to Hendra—which is why they are used to make antibodies. Testing the efficacy of this treatment required exposing additional horses. “It is difficult to describe working with a horse infected with Ebola,” according to the dry, cautious statement from Russia’s chief biowarfare man at the time, a lieutenant general named Valentin Yevstigneyev, in the Ministry of Defense. No doubt he was right about that. A horse can be nervous and jumpy, even if it’s not suffering convulsions. Who would want to get close with a needle? “Under normal conditions this animal is difficult to manage and we had to work in special protective gear,” said General Yevstigneyev. What he meant by “we” might be broadly interpreted. He was a high officer and military bureaucrat, not likely pulling the latex mitts onto his own hands. “One false step, one torn glove and the consequences would be grave.” Makovetskaya had evidently taken that false step. Or maybe it wasn’t her mistake so much as the twitch of a sensitive gelding. “She tore her protective gloves but concealed it from the leadership,” by General Yevstigneyev’s unsympathetic account, “since it happened just before the New Year holidays.” Was he implying that she hadn’t wanted to miss seasonal festivities while sitting in quarantine? He didn’t mention a needlestick, or a scratch, or an open cut beneath the torn glove, though some such misfortune must have been involved. “As a result, by the time she turned to a doctor for help it was too late.” The details of Makovetskaya’s symptoms and death remain secret.

  Another Russian woman stuck herself with Ebola in May 2004, and about this case slightly more is known. Antonina Presnyakova was a forty-six-year-old technician working at a high-security viral research center called Vektor (which sounds like something from Ian Fleming) in southwestern Siberia. Presnyakova’s syringe carried blood from a guinea pig infected with Ebola virus. The needle went through two layers of gloves into her left palm. She immediately entered an isolation clinic, developed symptoms within a few days, and died at the end of two weeks.

  These three cases reflect the inherent perils of doing laboratory research on such a lethal, infectious virus. They also suggest the context of concerns that surrounded America’s closest approach to a home-grown case of Ebola. This one occurred also in 2004, just months before the death of Antonina Presnyakova.

  18

  Kelly L. Warfield grew up in a suburb of Frederick, Maryland, not many miles from Fort Detrick, the US Army base devoted to medical research and biodefense within which sits USAMRIID. She was a local girl, bright and curious, whose mother owned a convenience store just outside the Fort Detrick gate. Helping her mom since she was a middle-schooler, Kelly first saw and spoke with scientists from the disease-research institute when they stopped into the store to buy Diet Coke, quarts of milk, Nicorette gum, Tylenol . . . whatever it is that top-level, Army-affiliated virologists buy. Unlike your average young convenience-store clerk, Kelly herself had a strong early aptitude for science. During high-school summers she worked in a government institute of standards and measures. After her freshman year of college and each summer until graduation, she served as a laboratory assistant at the National Cancer Institute, which had a branch on the grounds of Fort Detrick. She finished a bachelor’s degree in molecular biology and considered her options for grad school. Around the same time she read The Hot Zone, which had recently been published.

  “I’m a Hot Zone kid,” Warfield told me much
later. She couldn’t vouch for the book’s scientific accuracy, she added, but its effect on her then was galvanic. She was inspired by one of the main characters, Nancy Jaax, an Army major and veterinary pathologist at USAMRIID, who had been part of the response team at the infected monkey house in Reston. Warfield herself hoped to return to Fort Detrick after graduate school and join USAMRIID as a scientist—if possible, to work on Ebola virus.

  She looked for a doctoral program that would teach her virology and found a good one at Baylor College of Medicine, in Houston. An entire department at Baylor was devoted to viral research, with two dozen virologists, some of whom were quite eminent, though none dealt with such high-hazard pathogens as Ebola. Warfield found a place in the lab of a mentor there and began studying a group of gastrointestinal viruses, the rotaviruses, which cause diarrhea in humans. Her dissertation project looked at immune response against rotavirus infection in mice. That was intricate and significant work (rotaviruses kill a half million children around the world every year), though not especially dramatic. She got experience in using lab animals (especially mice) as models for human immune response to viral infections, and she learned a bit about making vaccines. In particular, she gained expertise in a line of vaccine development using viruslike particles (VLPs), rather than the more conventional approach, which uses live virus attenuated by laboratory-induced evolution. VLPs are essentially the outer shells of viruses, capable of inducing antibody production (immune readiness) but empty of functional innards, and therefore incapable of replicating or causing disease. VLPs seem to hold high promise for vaccines against viruses, such as Ebola, that might be too dangerous for live-virus vaccination.

  It took some time for Kelly to achieve her dream, but not much, and she wasted none. With the doctorate finished, twenty-six-year-old Dr. Warfield began work at USAMRIID in June 2002, just days after her graduation in Houston. The Army’s institute had hired her, in part, for her VLP skills. Immediately she enrolled in the Special Immunizations Program, a punishing series of shots and more shots required before a new person can be cleared to enter the BSL-3 labs. (BSL-3 comprises the laboratory suites in which researchers generally work on dangerous but curable diseases, many caused by bacteria, such as anthrax and plague. BSL-4 is reserved for work on pathogens such as Ebola, Marburg, Nipah, Machupo, and Hendra, for which there are neither vaccines nor treatments.) They vaccinated her against a whole list of unsavory things that she might or might not ever face in the lab—against Rift Valley fever, against Venezuelan equine encephalitis, against smallpox, and against anthrax—all within a year.

  Some of these vaccines can make a person feel pretty sick. Anthrax, for Warfield, was a particular disfavorite. “Ooof, terrible!” she recalled, during our long conversation at her current home, in a new suburb outside of Frederick. “That’s a terrible vaccine.” After all these challenges to her immune system, and possibly as a result, she suffered an attack of rheumatoid arthritis, which runs in her family. Rheumatoid arthritis is an immune dysfunction, and the medicine used to control it can potentially suppress normal immune responses. “So I wasn’t allowed to get any vaccines anymore.” Nonetheless, she was cleared to enter the BSL-3 suites, and then soon the BSL-4s. She began working with live Ebola virus.

  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 suddenly 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 his 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 blu
e-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.