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Story Publication logo June 30, 2015

Sierra Leone: Ebola Survivors May Be the Key to Treatment—For Almost Any Disease

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The current Ebola outbreak has been seen through the lens of terror and failure, but the untold...


LINA MOSES SENSED the ghost of Ebola as soon as her Land Cruiser entered the gate at Kenema Government Hospital. More than a hundred people had died in the treatment center here, an epicenter of the epidemic in Sierra Leone. A doctor who had treated them was buried on a hill overlooking the compound. When Ebola erupted in Kenema in May 2014, Moses was working here as an epidemiologist. She had never seen an Ebola patient. She could have fled home to New Orleans. Instead she stayed, fighting the outbreak and watching patients and friends die one by one.

Eventually Moses returned to the US. But now, two months later, she and one of the people she'd worked with, a physician named John Schieffelin, were back. Moses' driver eased the Land Cruiser up to her old lab, a single-story building tucked in the corner of the hospital compound. Workers appeared and started to help unload supplies. Moses, meanwhile, stepped out into the searing midday heat and stretched her legs. She saw six people sitting on the concrete steps of an office across from her lab. Some had been nurses and researchers at Kenema; a couple were part of a newly formed survivors' union. That's how they'd heard about Moses' mission.

All six had been infected with Ebola and survived. Hypothetically, that made them immune to the disease. That's why Moses had returned—to harness that immunity to try to ensure Ebola never killed anyone again.

After getting set up, Moses beckoned the survivors into the lab. A technician slid needles into their veins. The survivors' blood flowed dark red into purple-topped tubes. Moses watched in silence. Once that fluid had been a mortal danger; now it was a valuable commodity.

When the blood collection was over, Schieffelin passed a survivor outside who didn't recognize his doctor. Schieffelin covered most of his face with his hand, imitating the mask he'd worn in the wards. "Do you remember me now?" he asked, smiling behind his palm.

Later, Moses' boss, a virologist named Robert Garry, separated the cells they needed from the blood, washed them, and added a pink buffering liquid to each tube. Garry printed the date—January 12—and an ID number on each tube, then put the tubes into a Mr. Frosty-brand insulated container. Mr. Frosty, in turn, went into a portable freezer. Tucked safely inside, the samples chilled over the next four hours; it was crucial that they cooled slowly, so ice crystals wouldn't destroy the cells.

Finally, at 11 that night, Moses and Garry donned purple disposable gloves, popped open the lid on Mr. Frosty, and loaded the little labeled tubes into metal cases cooled with liquid nitrogen. She handled each tube for no more than a few seconds. Even the tiny bit of heat from her fingers could warm the cells inside enough to kill them and destroy the knowledge they contained. She shut the case, ready for a journey to the United States.

Past Ebola outbreaks killed as many as 90 percent of the people who got the disease. This most recent one did not—as many as 60 percent of infected people survived. Nobody is sure why. It might have had something to do with the particular strain of the germ; for example few people bled from their eyeballs this time. Or maybe it had to do with the better standard of care many of the infected received. Regardless, thousands of people got sick but didn't die. By definition their immune systems now make antibodies to the virus, proteins that can fight Ebola and win. Those antibodies are, essentially, the ideal medicine. Or rather they would be, if someone could unpack the biochemical manufacturing process that creates them.

Those cells Moses had collected contained the key, the blueprint for making that hypothetical drug. Scientists at Tulane University in New Orleans were waiting to try to do just that. And if they succeed? They might unlock not only a new treatment for Ebola but also a way to make new treatments for any virus, a broad-spectrum method for making drugs against diseases both common and rare, from influenza to Lassa fever. It would be a potent treatment option where today next to none exist.

Moses had tried this once before. In November she had collected another set of samples, but paperwork delays grounded the shipment in Sierra Leone. The cells thawed and died.

Now she was back at Kenema, back at the hospital where she had seen so many people die, to try again. Packed in liquid nitrogen, the blood would last 14 days—and it had to get safely back to the US. Moses had to get it onto a flight out of the airport near Freetown, the capital, by the day after tomorrow. But first Moses would have to get the samples through a countryside ripped apart by a biological apocalypse. The clock was ticking.

TWO DAYS LATER, Moses woke at 7 am, drank a glass of water for breakfast, and headed back to the lab. Today was transit day, and she still needed to print shipping labels and get money to pay for her driver and gas. Simbirie Jalloh, the logistics specialist at Kenema, had arranged for someone to deliver the money to Moses. That person was nowhere to be found. Jalloh was away at an Ebola task force meeting, and the only working printer was in Jalloh's office. Which was locked.

Moses paced around her transportation, a Toyota Prado SUV, as the town woke up. Car horns chattered on the road outside the hospital's front gate. Women with babies lashed to their backs hurried down gravel-strewn paths to appointments alongside hawkers selling cell phone chargers and sweet cakes from plastic tubs. Moses had hoped to be on the road by now; she had to arrive in Freetown by 11:30 am to get her samples onto a ferry across Tagrin Bay to the international airport in Lungi. From there they'd catch a flight to Brussels that night, and then another to Chicago and then finally New Orleans. Freetown and Lungi are only about 200 miles northwest of Kenema, but that still meant a four-hour drive on a good day. The epidemic was still raging through Sierra Leone, so there were Ebola checkpoints along the way, where officials tested everyone for fever.

The morning dragged on; Ensah, the facilities guy, arrived at 8 and let Moses into Jalloh's office. Moses sweated as she printed the shipping labels—it was already 80 degrees—and affixed them to the two bullet-shaped dry shippers with packing tape. But she still didn't have the money.

By 8:30, Moses was panicking. Her driver, John Sesay, was sitting on a bench under a palm tree. He calls her Dr. Moses—though she's a doctor of nothing practical—and she calls him Dr. Sesay, a doctor of driving. But Moses was in no mood for jokes. "I can't wait for the money," she snapped. "John, let's go."

Sesay jumped up, surprised: He usually got paid first thing in the morning. But he could tell Moses was on edge and didn't ask any questions. "Yes, Dr. Moses," he said. Moses loaded the shippers, each 25 pounds of coolant and metal about the size of a party keg, into the rear of the SUV.

Geared up, the Toyota pulled out of the hospital gates with 30 blood samples—from the six who'd been waiting for Moses in the Kenema courtyard and 24 more—all frozen in liquid nitrogen. Moses dialed a friend in Bo, the next town along the road, and asked for $400, borrowed from money Moses herself had lent to pay for kids' school fees.

Forty minutes later, Sesay pulled into a gas station just outside Bo, where Moses' friend was waiting with a bag of cash. But the pumps were out of diesel. So, too, were the next two stations they passed. They saw a man on the roadside selling fuel from water bottles, and Moses thought about it. The whole town might be out. But it would take forever to fill the tank from the little 1.5-liter containers. With an eighth of a tank left, they decided to check one more station, a run-down shop in the center of town.

They were in luck—the attendant gassed up the Toyota, Moses paid him, and they were on their way at last. It was almost 10 am. They had an hour and a half to go 150 miles.

BEFORE EBOLA STRUCK, Moses had been in Sierra Leone for five years, finishing her dissertation for Tulane and working with a consortium of researchers and institutions studying viral hemorrhagic fevers. At Kenema, Moses led a team of people doing surveillance on the prevalence and spread of Lassa, a fatal disease that's common in Sierra Leone but that most people in the West have never heard of.

In late March 2014, Moses' network started getting reports that a different viral hemorrhagic fever had crossed from Guinea into Sierra Leone: Ebola. She sent a couple of surveillance officers to check out the reports at a place called Buedu, but they came back having found no sign of the disease. Moses and a Kenema doctor, Sheik Humarr Khan, were trying to figure out what the field team had missed when they realized that there were probably a lot of villages with similar names. Khan pulled out a map and almost immediately they spotted a village called Boidu, 30 miles northwest of where they'd sent their surveillance guys. It was on the border between Sierra Leone and Guinea. "Lina, I think you should go there," Khan said.

After two days on dirt roads, Moses and a team got to Boidu. When she arrived, she saw a fresh pile of red dirt behind one of the houses: a grave. Her team started to ask the locals questions. Yes, a man had been buried here; yes, his son had died too, after helping him. The villagers said they had washed the dead men carefully before burial—as was customary.

Moses and the team pressed. Who cared for the men? Who touched their bodies? The villagers started to pull back. "You could see them start to realize, 'Oh shit, we did something wrong,'" Moses says. They started to change their stories. They said that an aunt had carried the sick son to a clinic for treatment—then said she'd had nothing to do with him. Moses hoped they'd still escape the disease somehow. But if it was Ebola, it was going to spread.

A couple of months later, the lab at Kenema received a new sample to test: blood from a sick local woman. She was positive for Ebola. So were two patients who had been admitted. Khan called the staff together. "Guys, come around," he said. "Ebola is with us in this hospital at last."

After that they poured in, day after day. Lassa and Ebola have some symptoms in common, including (sometimes) Grand Guignol-like bleeding, so Moses and the Kenema team thought they were prepared. But the surge overwhelmed them. Doctors set up a makeshift tent and took over a second ward to care for the newcomers. Patients were stacked three to a bed, racked with fever and pain.

Ebola is transmitted through any bodily fluid—blood, sweat, tears, semen, mucus, vomit. Kenema hospital had protective Tyvek suits, gloves, and masks on hand, but the gear was poorly distributed, and doctors and nurses started to fall ill and die themselves.

That outcome wasn't foregone. Though their expertise hadn't yet reached Kenema, aid groups like Doctors Without Borders were learning to treat Ebola while keeping health workers safe. They were also learning to save people who were already infected.

When the virus enters the body, it induces a total overreaction in first-responder immune cells. They send a torrent of panic signals that trigger a physiological disaster: fever, pain, vomiting, diarrhea, and—if left unchecked—death. The infection moves so fast that the body's second phase of the immune response—making antibodies that attack the virus—never has a chance to kick in. So Doctors Without Borders clinics figured out that they could reduce Ebola's lethality with intense supportive care: Keep patients alive long enough—with antibiotics, acetaminophen and other pain medications, vitamins, and oral or intravenous fluids—and their bodies would have time to start fighting the disease. The protocol treats dehydration and weakness and, combined with soft drinks, food, and water, helps the majority of patients survive. "There's nothing more joyous than when someone says, 'I'm hungry, give me rice.' Then you know you're going to be OK," says physician Kirrily de Polnay, who worked with Doctors Without Borders.

In the meantime, as people get sicker the bodily fluids that carry the disease start pouring out of them in ever greater volumes. So everything about a Doctors Without Borders Ebola treatment center is designed to cut worker risk. A water system dispenses two strengths of chlorine solution through dedicated taps. Access to patients is strictly controlled; workers get to the ward through only one entrance, and they leave through a single exit where they are sprayed down with bleach. Two layers of fences separate the sick from the well by 2 meters—far enough to protect from projectile vomit. And rules govern everything: from which chlorine solution is used to wash boots (0.5 percent) or dishes (0.05 percent) to how long workers can stay inside with patients (one hour).

At the start of the outbreak, Kenema Government Hospital didn't have any of those precautions in place. They weren't ready. Patients were leaving the wards to lie on the sidewalks, trying to escape the heat and misery inside.

One day in June, Moses saw a nurse, Alex Moigboi, caring for patients in the Ebola ward. He was wearing completely inadequate gear: just a plastic apron and a pair of gloves over his scrubs.

"Alex, what are you doing in there?" Moses shouted.

"What else am I supposed to do?" Moigboi shouted back angrily. He hadn't been able to find the gear.

Moses ran to her lab to get it. She told Moigboi to call her next time before charging into the ward. It didn't do any good. Like so many of Moses' friends, Moigboi died a few weeks later. Khan, too, got infected. He died on July 29. They buried him in a grave overlooking the lab.

Moigboi's death hit Moses especially hard. He was such a sweet, selfless kid. He was one of the first nurses to become infected, because he was one of the most dedicated, dutifully caring for patients when everyone else was scared away by the impossibility of the task. "You think that the really good people are going to pull through—that there's got to be some justice," Moses says.

Eventually aid groups arrived and started implementing measures they hoped would alleviate the problems. The World Health Organization built chlorinating stations throughout the Ebola unit. Doctors Without Borders helped with water and sanitation. The Red Cross helped with screening patients.

Still more nurses got sick. In the fall of 2014, Kristian Andersen, one of Moses' colleagues back in the US, was just getting off a phone call with a friend in Kenema's Ebola ward. Andersen, a geneticist at the Broad Institute in Cambridge, a research center affiliated with Harvard and MIT and part of the same consortium of virus-hunters as Tulane, had helped with the diagnostic lab at Kenema. Back in Cambridge, he was using leftover diagnostic samples to study the genetic sequences of the Ebola virus. As Andersen hung up the phone, he thought, "We've got to do something."

It dawned on him: The patients held the answer. If they survived, they carried antibodies that targeted the very viruses that had almost killed them. The samples he'd been working with didn't contain antibodies, but if he could get blood from survivors, he might be able to figure out how to make the same antibodies that their immune systems had produced. It would not be easy or fast, but he couldn't stand by while more people lost their lives—if not in this outbreak, then in the next one, or the next one after that. It was time for a new plan.

SESAY SPED OUT of Bo, trying to make up time. Half an hour later, Moses got a text from Augustine Goba, who ran the lab at Kenema. Freetown was under quarantine. "Go straight to the Lungi airport," Goba wrote. "They do not have a pass for the shipment to go out tonight." In other words, it didn't matter if they got to Freetown in time for the ferry, because the ferry wouldn't take the samples. That was actually good news. Moses preferred to stay in control of the samples for longer, and if they made for the airport directly they had more time. Sesay adjusted their course, and for the first time that day Moses relaxed, watching the villages and countryside out the window. It was mostly small fields hacked out of the tropical forest. But she couldn't see anyone out planting or harvesting. Every hour or so the car would pass another Ebola treatment center or a fenced-off cluster of tents—a quarantined holding place for patients suspected of having the disease.

At the turnoff for the airport road, Moses looked for the long trains that usually ran alongside, pulling loads of iron ore to ships in the harbor. This one sign of progress in Sierra Leone's faltering economy usually heartened her. But no trains passed. Ebola had switched the country's economy off.

At 2 pm, Sesay pulled up to the loading dock at the airport. A shipping agent—Moses only knew him as Richard—emerged from the office. His red dress shirt and crisp black pants implied his official capacity. Moses opened the Toyota's rear door and reached for the dry shippers safe inside. But Richard, aghast at the idea of a white woman performing manual labor, grabbed them. Moses reached into the Prado for the paperwork and handed off four copies of the documents affirming that her samples were free of Ebola, tested before freezing at Kenema. Now the shipping agent was responsible for getting the samples on the flight. It was supposed to depart at 7:20 pm. The next flight wouldn't leave for four days.

Moses checked in to a hotel half a mile away. It was high-end by Sierra Leone standards—the room had air-conditioning and a flatscreen TV. Exhausted but too nervous to rest, Moses sat on the double bed and opened her laptop. She clicked to a spreadsheet and started typing in data from a Lassa study, a task she could do with half her brain while the other half worried about the samples. She texted Richard: "Have the packages been cleared for shipment?" He didn't reply.

Moses had been walking down to the hotel lobby, which had Wi-Fi, to check her email. Six o'clock came and went, and she still didn't know whether the samples were on the plane. Moses tried to stay calm. Her samples had to be loaded in less than an hour or they'd miss the flight. This was where things had gone wrong the last time. Researchers halfway around the world were watching their phones for word that they'd have material to work with. The sooner they could start, the sooner they could save lives. An undotted i or uncrossed t could sink the project. Again.

Schieffelin called. Moses told him what was going on but asked him to keep it quiet. "I'm not going to tell anyone unless it looks like it's become an actual problem," Moses told Schieffelin. "I don't want anyone freaking out."

"That's probably a good idea," Schieffelin replied.

WHILE MOST PATIENTS in the recent Ebola epidemic had at best 60–40 odds of surviving, one group had much better chances: people evacuated to Western nations. "Supportive care" means something very different at a university teaching hospital in the US than it does in Kenema. The evacuated Westerners had ventilators, dialysis, and more comfortable digs.

Most of them also received at least one experimental treatment. Many such unproven drugs exist for Ebola. Clinical use didn't help validate them because different patients with different symptoms got them at different stages of the disease, often in combination with other therapies both proven and unproven.

One popular approach, though, has been the use of serum—fluid derived from the blood of Ebola survivors, which contains antibodies against the disease. Antibodies are big Y-shaped proteins that kill invaders like bacteria and viruses. Any animal with bones has an immune system that makes them, and they're essentially programmable; the immune system reads the proteins in the shells of germs and builds antibodies specific to them. Once your body knows how to make antibodies specific to a disease, it never forgets, which is why if you had chicken pox as a kid, for example, you don't get it again.

So physicians use survivor serum in the hope that amid the trillions of antibodies an adult human can make, the ones that fight a specific disease will be in the mix. It's not a new idea. The doctors who fought a 1995 Ebola outbreak in the Democratic Republic of the Congo tried survivor serum in eight patients. But the stuff is difficult to gather and distribute, and no formal trial has ever proved its benefit.

Over the years, researchers have begun making antibodies in labs. They infect mice or rabbits with the pathogen in question, then stick the cells from the animals' spleen—the spleen being a font of antibody generation—to blank, modifiable antibodies derived from a particular kind of tumor cell. From there, scientists find and purify the antibodies they need, using various screening techniques until they have a batch that fights exactly the disease they want. Drugs based on these so-called monoclonal antibodies have become a lifesaving mainstay of modern medicine, fighting illnesses as disparate as cancer, arthritis, and lupus. But it takes a long time to make them, partly because of the years it takes to find and reverse-engineer the best antibodies in lab animals and cells.

Still, this idea is the principle behind an antibody cocktail called ZMapp, which seven Ebola patients received in 2014. To make it, scientists infect mice with an Ebola virus from a previous outbreak and then collect the mice's antibodies, choose the ones that seem to work best, and purify copies to give to humans.

Back at Tulane, an immunologist named James Robinson was already planning to try to make a better ZMapp—from humans instead of mice. First he'd have to copy DNA from survivors' B cells, the white blood cells that make antibodies. Then he'd insert that DNA into human embryonic kidney cells in the lab. That would turn those kidney cells into "clones" of the B cells—some of which would make antibodies to Ebola.

Once he knew which cells, Robinson could sequence their DNA and find the specific genetic instructions for making the right antibodies. Then a colleague could copy those genes into yet another round of cells, these derived from mouse-myeloma cells—a type of mouse cancer that turns out to be particularly well-suited to pumping out antibodies. Those would make the actual medicine.

If it works, the resulting drugs will be tailor-made to combat the same virus that is causing this Ebola outbreak, which means it might work better than ZMapp. But the entire process could take months or years. And making antibodies isn't easy; that's why the miniscule supply of ZMapp ran out early in the epidemic.

In fact, antibodies are among the most expensive medicines in the world, costing as much as $500,000 per year for one person's course of treatment. That's a prohibitive price tag—especially for diseases like Ebola, which mostly kill people in poor countries. Rich people don't typically get Ebola, so drug companies will never be able to charge enough to recoup the astronomical cost of developing medicines for it.

Andersen planned to tackle this bigger problem at the Broad Institute. He had an idea for a shortcut: Instead of copying antibody-coding DNA into other cells, he'd sequence it and pick out the stretches that seemed most likely—according to a computer model—to make antibodies specifically tuned against Ebola. In theory, that would save months of work. You wouldn't need all those rounds of clones. You'd just find the Ebola antibody genes, put them into new cells, and start churning out a drug.

Andersen wasn't the first person to think of this angle, but no one has ever been able to pull it off. A human has hundreds of millions of antibody-making cells. Years ago, researchers could only sequence a few hundred of those cells at a time. Decoding the complete set would have taken way too long and been cost-prohibitive.

But the cost of sequencing genes has plummeted. And because places like the Broad Institute have so many sequencers, the process is much faster.

What Andersen has proposed doing would completely upend the economics and mechanics of the pharmaceutical development pipeline; if successful, he won't need to spend years in the lab to find antibodies against Ebola. He just needed human survivors; their bodies had already done all the work. Modern sequencing technology could find the information he needed.

Plus, if it works, Andersen's approach could become a faster, cheaper way to make new antibody medicines not just for Ebola but for any disease—bacterial, viral, anything a person's immune system might ever gin up an antibody against. If the process works for one pathogen, it should work for all of them. Antibody drugs wouldn't be haute couture anymore; they'd be ready-to-wear, cheap and widely available.

To test his hypothesis, though, Andersen needed one key ingredient: the blood of people who had survived Ebola.

BACK IN HER hotel room near the Lungi airport, Moses watched the clock on her laptop creep closer to 7:20 pm. That's when a plane would—hopefully—take off with her cargo. As the minutes ticked past, she heard nothing.

The time came and went; silence. No word on whether her shipment had made it on board.

Finally, at 7:45 pm, Moses reached Richard. Her samples were on their way.

But the next day, there was bad news: a one-day delay at the Brussels airport. Then there were more setbacks. When the dry shippers got to Chicago they spent two days making their way through customs. The packages should technically have stayed cold for another eight days after that, but they had been sitting in 80-degree heat for hours at the Lungi airport, and that had probably shaved a few days off the samples' shelf life.

Even though she knew she couldn't do anything about it, Moses would find her mind wandering back, again and again, to an image of her samples in transit somewhere, heating up degree by degree before anyone ever opened the box. She tried to put the idea out of her head.

Finally, on January 19, she got an email from Robinson, the Tulane researcher who would receive the parcel and begin disbursing its contents to the consortium: "The samples have been safely transferred to liquid-nitrogen storage tanks," he wrote. "What a relief!"

OF COURSE, THE task of developing an antibody drug against Ebola was even harder than getting blood from Sierra Leone to the US. Four months after Moses' samples reached New Orleans, Andersen stood at a whiteboard in a Tulane lecture hall, visiting his colleagues on the project. The survivors' samples were in a freezer one building away. This was the closest Andersen had ever been to them.

In fact, he hadn't even started working with them. In August, Andersen and a colleague at the Broad, a geneticist named Pardis Sabeti, had published a controversial paper that used data from Ebola gene sequences to calculate how fast the virus was evolving. Now, nine months later, Andersen was scribbling graphs on the whiteboard, defending his position in front of a room packed with many of the people working on understanding and fighting the disease—Moses, Robinson, and Garry among them.

But the debate was mostly technical. Everyone agreed that the longer the epidemic lasted, the more the Ebola virus would change. That meant stopping it soon, before it outran any new therapy, was all the more urgent. Andersen was on his way to a new job at the Scripps Research Institute in San Diego to attempt just that. He wanted to get to work.

Robinson, meanwhile, had gotten a little further. He'd been copying DNA from the survivors' samples and pasting it into cells in a lab. So far, it seemed to be working. His lab had become a mini factory full of cells churning out antibodies. The method was supposed to take longer than Andersen's, but for the moment Robinson was ahead.

Moses, watching Andersen write equations on the board, wasn't getting her hopes up too much. Even as the epidemic in West Africa had waned, it stubbornly refused to end. Some scientists had begun to wonder if Ebola would become endemic, flaring up in some spots for years. If that happened, a drug would help, but watching her colleagues bat around mutation rates reminded her that they had a long way to go.

That was just the nature of the job, though. Sometimes Moses thought that working in Sierra Leone was like spending time in a biosafety level 4 laboratory—the high-security fortified lab in which scientists handle the most deadly contagious diseases. Before you even go inside a BSL-4 lab, you have to plan even the tiniest part of your experiment: which forceps you'll use, how much distilled water you'll need. Because once you suit up and go in, you can't just pop out and grab something you forgot. You have a plan and a purpose. So you have to believe going in that you know what you're doing, that you're there for a reason. And you stay inside until you've finished the job.


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