Crisis in the Red Zone

by Richard Preston

  Pardis Sabeti was furious about the decision. She didn’t speak publicly about her feelings, but at the Broad Institute her colleagues heard her cursing profusely, in a loud voice, as she moved around the offices near the Ebola War Room. Humarr Khan had been a member of her team and a dear friend, and he had been denied a drug that could have saved his life.

  Dan Bausch was quoted in the Times article as saying he disagreed with the decision by Doctors Without Borders, and said he thought that Khan should have been asked for his own opinion. “Dr. Khan was the perfect patient, I think, to understand the complexities of that gray area,” he said. He also said it was a close call and that he respected the decision of the doctors on the ground. None of the scientists, doctors, officials, or camp managers knew that Khan had been reading up on the experimental anti-Ebola drugs and vaccines, was familiar with the data on them, and considered ZMapp to be his first choice for treatment. It is being reported here for the first time.

  The Kailahun camp managers have been reluctant to discuss publicly the reasons for their decision not to offer the drug to Khan. I learned from three different physicians with Doctors Without Borders that members of the Kailahun team had been deeply traumatized, and wouldn’t even talk about their experiences privately with other members of Doctors Without Borders. Eventually Anja Wolz, who had been the clinical manager of the Kailahun Ebola Treatment Center, agreed to speak with me; I reached her on the phone while she was at the Brussels center of Doctors Without Borders.

  “It has been quite difficult for me to think about it,” she said. “Our fear was that if we gave the medication to Dr. Khan we wouldn’t know the outcome. ZMapp had never been tested in a human, and it meant we would use Dr. Khan as a guinea pig.” She had talked with Gary Kobinger, asking him for his thoughts about the drug. Since he had helped develop the drug, he couldn’t advise Anja Wolz to give it to Khan. “Gary said, ‘It’s for you in the field to decide. You can decide what is best for you and your team.’ ” Kobinger had offered to relieve her of the ethical responsibility for the decision. “If you want, we can decide for you,” Kobinger said to Wolz, meaning that an international panel of experts would weigh in with a recommendation. Wolz told Kobinger that she would assume moral responsibility for the choice.

  Her father called her constantly, trying to encourage her. She said to him, “Papf, people are dying and we can’t do anything about it.” It was impossible to explain to anyone what it felt like to work in an Ebola treatment center, when there were no treatments, when children and teenagers were dying, alone, without any family around them. She had to consider the danger of violence if Khan died; there was violence happening already in areas not far from the camp; the lives of all the patients and staff were in her hands. She had once given up cigarettes but now she was smoking them constantly. She kept hearing promises that the SOS medevac jet would soon take Khan to Switzerland, where he could be given ZMapp without endangering lives at the camp. In the end, all the promises were worthless and SOS refused to take Khan on board. Not long after Khan died at the camp, Wolz learned that two Americans had apparently been saved by the same course of ZMapp that she and her team had decided not to offer to Khan. “I felt, oh, oh, have we done wrong? Now, knowing that ZMapp works, it was probably the wrong decision. It was the best I could do given the facts we had at the time, and I still stand by my position. It was something so emotional, so difficult. There were a lot of things I tried to forget for a long time.” Her voice faltered and broke, and she began to weep.

  * * *

  —

  Through the late summer of 2014, Pardis Sabeti and her group continued to read the genomes of the Ebola swarm, and would publish the data in real time on the website of the National Center for Biotechnology Information, so that scientists anywhere in the world could see the results immediately. Then, in late August, Sabeti’s group published a paper in Science detailing their results. They had sequenced the RNA code of the Ebolas in the blood of seventy-eight people who lived in and around Kenema during three weeks in May and June, just as the virus was starting chains of infection in Sierra Leone. The team had run vast amounts of Ebola code through the machines and had come up with around two hundred thousand individual snapshots of the virus in the blood of those seventy-eight people, and they had watched the virus change as it entered the human species.

  Sabeti’s group also found that the virus had started in exactly one person. As it spread from this first person to the next, and to the next, the swarm mutated steadily, its code shifting as it explored the human species. As the virus jumped from person to person, about half the time it had a mutation in it. Most of the mutations didn’t change the proteins in the virus, but every now and then one did, and the virus became slightly different. By the time the virus reached Sierra Leone and got into the bodies of the women who had attended the funeral of Menindor, the faith healer, the virus had already mutated into two genetically distinct swarms. Both lineages of the virus moved out of the funeral of Menindor and across Sierra Leone. But only one of the two strains at Menindor’s funeral ended up infecting most of the victims in West Africa. This was the Makona strain, the hot Makona, the dominating mutant.

  By September, Pardis Sabeti could see the Makona strain in operation, but she didn’t yet know whether there was anything truly different about it. Was there something unusual about the Makona strain? Was it more deadly in humans, or more infective, or both? Why was the Makona strain sweeping through West Africa when the other strains were fading away? She still didn’t have an answer to that last question—she still didn’t have visibility into the character of the Makona strain. She could read all the letters of code in the strain, but she couldn’t yet understand the meaning of those letters.

  Some of Ebola’s mutations had made the virus less visible in tests. “It shows that you can analyze Ebola in real time,” Sabeti said to me, in mid-September. “This virus is not a single entity. Now we have an entry into what the virus is doing, and now we can recognize what we are battling at every point in time.” The Science paper included five authors who died of Ebola, including Humarr Khan, Ebola ward supervisor Auntie Mbalu Fonnie, and senior nurses Alex Moigboi and Alice Kovoma. Many other members of the Kenema team were co-authors of the Science paper, including Michael Gbakie and Lansana Kanneh, who had risked and nearly lost their lives exploring the Makona Triangle for people infected with Ebola. “There are lifetimes in that paper,” Sabeti said.

  CURED

  ATLANTA, GEORGIA

  First two weeks of August, 2014

  Kent Brantly made it alive to Emory University Hospital, but he was still very sick. His illness seemed comparable to what Hensley had said happens to monkeys—“They may look better but then seem to slip a bit.” The drug had hammered down the virus in his body but certainly hadn’t eliminated it. Brantly was given two more doses of ZMapp—this was Course No. 3, flown in from Kentucky. He continued to improve; he was also getting world-class medical care by his team. Brantly’s wife, Amber, had arrived, and they were able to talk with each other through a glass window; he had to remain inside the biocontainment unit.

  Nancy Writebol had received her first dose of ZMapp at ELWA Hospital. Afterward she remained in bed in her house, being cared for by Samaritan’s Purse doctors and staff. She stayed alive. A few days later, Samaritan’s Purse doctors administered a second dose of ZMapp to her. At this point all three doses of Course No. 2—the course that might have been given to Humarr Khan—had been used up. Nancy Writebol was still at ELWA Hospital and needed a third dose.

  After the Phoenix Air jet had carried Kent Brantly to Atlanta, it turned around and flew back to Liberia, where it picked up Nancy Writebol and carried her to Atlanta as well. She, too, was placed in the biocontainment ICU at Emory and was tended by the Emory team. There, she received her third dose of ZMapp—this was the last of the three doses of Course No. 3.

  Nancy Writeb
ol had a rough time as she fought Ebola in the Emory unit. Her recovery went slowly, but on August 19 she was discharged from the hospital and went home with her husband, David. She requested privacy and didn’t want media attention. She later said that she couldn’t remember much about her illness. Ebola can cause amnesia, and many Ebola survivors remember little or nothing of their time spent in the embrace of the virus.

  Kent Brantly made steady improvement. But as long as the virus was in his bloodstream it was present in the United States. There was always a danger, no matter how small, that the virus could escape from Brantly’s body. For that reason, the Centers for Disease Control monitored his blood tests. On August 20, Brantly was declared free of the virus, and he walked out of the biocontainment unit at Emory, and he and his wife wrapped their arms around each other for the first time in months. The next day he was discharged from the hospital. He was thin, but he was on his feet and smiling. He walked through two rows of medical staff giving him applause, and he went home to Fort Worth. Kent Brantly and Nancy Writebol credit their survival to outstanding care by their doctors, to ZMapp, and to the power of God.

  * * *

  —

  After Kent Brantly and Nancy Writebol each got a course of ZMapp, there were four remaining courses in the world. A seventy-two-year-old Spanish priest named Miguel Pajares caught the virus in Liberia. He was airlifted to Madrid, where he was given one dose of ZMapp from Geneva Course No. 1, but he died soon afterward.

  A British nurse named Will Pooley was working at the Kenema hospital as a volunteer. He broke with Ebola, and on August 24 he was flown to London in a plastic biohazard tent installed in the cargo hold of a Royal Air Force Boeing Globemaster transport aircraft. He was put in a biocontainment unit in a hospital in London and given the remaining two doses of Course No. 1. Pooley’s Ebola disease turned around in twenty-four hours, and he recovered fully.

  Larry Zeitlin sent Courses Nos. 4, 5, and 6 to ELWA Hospital in Monrovia, where they were administered to three African doctors who were sick with Ebola, named Abraham Borbor, Zukunis Ireland, and Aroh Cosmos Izchukwu. Dr. Borbor died but the others lived. At this point, Mapp Bio announced that all the available ZMapp in the world had been used up, all six courses of it.

  * * *

  —

  The drug very clearly rescued Kent Brantly from imminent death. He was in the Ebola crash, and yet thirty minutes after ZMapp started hitting his bloodstream he sat up in bed. Within an hour, he was walking. How can this be possible? Only a very small amount of the drug had reached his bloodstream.

  It seems that ZMapp swiftly killed every Ebola particle that was drifting in his bloodstream. It acted on Ebola the way a powerful insecticide freezes a nest of wasps. I asked Larry Zeitlin, the president of Mapp Bio, how it was possible for a very small amount of ZMapp to kill so many Ebola particles in just a few minutes.

  Zeitlin wasn’t surprised. He had seen antibodies do the same thing with sperm cells. After a bit of calculation, he said that thirty minutes after the drug began dripping into Brantly’s arm, each individual Ebola particle in Brantly’s bloodstream was surrounded with about thirty thousand individual antibodies—enough antibodies to nuke the particle and guarantee its death.

  Brantly’s blood was passing through his kidneys, and the kidneys are good at straining foreign particles out of the blood. Sixty minutes after Brantly was given ZMapp, he was in the bathroom peeing dead Ebola out of his body.

  But that wasn’t the whole story. Cells all through his body were factories squeezing out Ebola particles by the thousands. The antibodies also stuck to the Ebola hairs coming out of the cells, and killed the cells. Larry Zeitlin explained it this way: “With the caveat that we are in the area of total speculation—off the map, there be sea monsters here—there is a growing body of evidence that viral therapy with antibodies works by killing infected cells. This makes sense since you are stopping the factories from churning out virus rather than just killing whatever comes out of the factories.” Bomb the factories that make the bombs, and you stop the bombs from being made. The patients needed three doses of ZMapp because the first dose wasn’t able to kill every single infected cell. Some cells continued to pour out Ebola particles, but they got killed in the waves of ZMapp.

  By early September, with the six official courses of ZMapp having been used up, Kentucky BioProcessing went into crash production of ZMapp, but the manufacturing process was very slow and yielded only small amounts of the drug. The secret course of ZMapp, though—Course Zero—remained unused. It sat in its freezer vault somewhere in the United States.

  NATIONAL INSTITUTES OF HEALTH, BETHESDA, MARYLAND

  Mid-August 2014

  Officials at the National Institutes of Health combed through Lisa Hensley’s electronic communications. “When they start looking at somebody’s emails,” Gary Kobinger said, “it’s close to a done deal that the person’s going to be fired.” However, one fact quickly became clear. The NIH had not provided the drug to the American patients. Course No. 2 of ZMapp had been the property of the government of Canada. Gary Kobinger, a Canadian government scientist, had donated it to Samaritan’s Purse for compassionate use in an American citizen.

  Another fact came into play. Lisa Hensley had been on a deployment with the Department of Defense. She had been operating inside the military chain of command. The top CDC officer in Liberia, Dr. Kevin de Cock, had asked Hensley to review the best drug options for Samaritan’s Purse: She had been subordinate to him in the chain of command. The U.S. ambassador to Liberia, Deborah Malac, had authorized the helicopter flight, and a Marine Corps officer, Lt. Col. Bryan Wilson, had asked Hensley to go on the flight as a representative of the U.S. government. The U.S. Ambassador has control over military people who serve in the Embassy, and Hensley’s flight to get the ZMapp had been a diplomatic and military mission organized by the Embassy. One last thing was important. Two lives had been saved, and Hensley had made some small contribution to the effort. She hadn’t gone rogue. Or had she? In a time of crisis, in the fog of a virus war, nobody is really in control. In any event, the investigation cleared Hensley of any wrongdoing. “Lisa did the right thing,” Pardis Sabeti commented. The top management of the National Institutes of Health ultimately came to the same conclusion, and Hensley kept her job.

  CAMBRIDGE, MASSACHUSETTS

  September 22

  On a warm day in the fall, Pardis Sabeti was in the Ebola War Room at the Broad Institute, running a meeting with a group of colleagues. Glass buildings of biotech and pharma companies filled the view in the windows, with the Charles River and Beacon Hill in the background. Humarr Khan had been dead for over a month. Ebola was continuing its expansion in West Africa. Nevertheless, it had been stopped in Nigeria. “The virus hasn’t gone into exponential growth in Nigeria,” Sabeti said to the group, “so we have a little bit of a respite.”

  Sabeti was certain that Ebola was soon going to show up in the United States, carried there by air travelers. She said that hospitals and health authorities weren’t ready for the virus. Consequently, Americans were going to die of Ebola.

  * * *

  —

  A week later, at Texas Health Presbyterian Hospital in Dallas, a man named Thomas Eric Duncan showed up in the emergency room with a headache, nausea, and a fever of 100.1. He’d been living in Monrovia, Liberia, in a rented room, and had recently arrived in the United States. After hours of tests, Duncan was given a prescription for antibiotics and discharged. Two days later he showed up at the same emergency room again, this time in an ambulance. Doctors learned, then, that he’d been living in Monrovia, which made them suspect he might have Ebola. They reported his case to the CDC.

  Nurses and doctors at Texas Health Presbyterian Hospital gave care to Duncan while he was under suspicion of having Ebola. They got splashed with his body fluids, but they had not been wearing standard Tyvek biohazard suits, HEPA masks, or
shoe coverings, though they had put on cotton surgical masks, gowns, gloves, and eye protection. In other words, they treated Ebola too casually. Duncan vomited on the floor, and the staff may have tracked Ebola particles around the hospital’s corridors on their shoes. On September 29, a nurse named Nina Pham gave care to Duncan, and the medical records show no evidence that she wore any kind of protective gear. The CDC tested Duncan’s blood and confirmed that he had Ebola; he died a week later.

  Shortly after Duncan died, Nina Pham broke with Ebola. She was transferred to the biocontainment ICU at the NIH hospital in Bethesda, Maryland, for treatment, and survived. One of her principal physicians, who spent long hours at her bedside, was Anthony Fauci, the head of the National Institute of Allergy and Infectious Diseases. Another nurse from Texas Health Presbyterian Hospital, Amber Vincent, had also contracted Ebola from Thomas Eric Duncan. She traveled on a Frontier Airlines flight from Dallas to Cleveland while she was running an Ebola fever, and then returned to Dallas on another Frontier flight. Several hundred people were on those flights. Frontier Airlines deep-cleaned the planes four times and put the flight crews into isolation for twenty-one days. Nurse Vincent ended up at Emory University Hospital, and she also survived.

  On Friday, October 17, a doctor named Craig Spencer, who’d been working as a volunteer for Doctors Without Borders in an Ebola treatment unit in Guinea, landed at Kennedy International Airport in New York, having finished his tour of duty. He felt deeply exhausted but otherwise okay. The next Tuesday, he walked along the High Line—a park that follows an elevated train track in Manhattan—and drank coffee at a café. He visited a food shop and ate meatballs, he rode the subway, he went bowling. On Thursday Dr. Spencer woke up feeling strange. His respiration was fast—he was breathing rapidly—and he was warm. By evening, a blood test had confirmed he had Ebola. New York City health officials were uncertain about how to biocontain him—cocoon him so he couldn’t transmit the virus to anyone else in New York City. “It was clear they didn’t have a plan,” Spencer later said to New York magazine.