In October, scientists set out to do something unprecedented – conduct a drugs trial during an epidemic to find a treatment for a lethal disease. Could they make history and change the way we deal with outbreaks?

The border crossing did not look encouraging. Dense tropical forest spilled over the banks of the rushing Mano river, which divides Guinea from Liberia. Three scientists from Oxford University – Jake Dunning, 38, Peter Horby, 47, and Laura Merson, 37 – stood on the bank and watched as the boatman used a plastic canister to bail out brown water from the bottom of the canoe. They then climbed in with their bags – they had no time to lose.

It was 20 October 2014 and the travellers carried passports with visas for the three countries worst afflicted by the Ebola epidemic: Liberia, Guinea and Sierra Leone. They also carried mission papers, which gave them government approval to cross border posts that had been closed in an attempt to stop the spread of the disease.

Once they reached the far bank and stepped out onto Liberian soil, a military border guard came out of his concrete bunker to inspect their documents. He was under instruction to take the temperature of every traveller, to check for the fever that is the first symptom of the Ebola virus. The guard had a log book but no thermometer, so he looked each of the travellers in the face, then wrote down his own estimates. Horby, a professor who specialises in tropical disease outbreaks, thought it wiser to say nothing. “I didn’t fancy telling a military guard at a remote border crossing that he was doing the wrong thing,” he told me by Skype from Sierra Leone a few weeks later.

The little band of scientists had flown to Guinea on 16 October to do something that had never been successfully done before – set up a trial of experimental drugs against an infectious disease in the middle of an epidemic. Because the Ebola virus does not exist at low levels in any population, unless you run a properly conducted trial while the storm is raging, you will never have drugs that are proven to be effective. The Oxford team’s trial would not only aim to find a drug that worked against Ebola but also to establish a blueprint for the way drug trials would be run during outbreaks in the future. This did not just apply to fighting Ebola: if the scientists were successful, their trial would develop protocols for testing drugs for any epidemic, be it Sars or flu.

Safe and effective drugs for Ebola were desperately needed. By mid-October, there had been nearly 10,000 reported cases of Ebola and nearly 5,000 people had died, according to the World Health Organisation (WHO) – although many epidemiologists believed the real death toll was two or three times higher. The epidemic was constantly shifting shape: as the numbers dropped in one area, the rate of infection flared up somewhere else. When a person got infected, fever, muscle pain and headaches progressed quickly to vomiting, diarrhoea and then internal and external bleeding. Within six to 16 days up to 70% of those with the Ebola virus were dead.

The Oxford scientists had 15 days to visit eight potential sites, spread across three countries paralysed by economic collapse, and where travel was limited by curfews and quarantine laws. They were looking for a treatment centre that fitted the exacting criteria for their trial. Horby described finding the right site as “like aligning the stars”. They needed well-designed buildings, internet connectivity, reliable power and plug sockets. They needed to be sure the drugs could be kept securely on site. “You’ve got a long list [of possible sites], but when you look at who fits all the criteria, you rapidly cross them off,” said Horby. “Finding one that’s easily accessible, got good infrastructure, international and local staff who are enthusiastic, good data management, good pharmacy, access to a good lab that’s willing to process research samples – and it’s got patients. There were hardly any that met all those criteria.”

The scientists had to move fast, but finding the right trial site was only part of the critical enterprise they were engaged in. In normal circumstances, getting a new drug from the lab to the pharmacy is an extremely slow process. Drugs need to be tested systematically on animals and humans before initial large-scale trials can begin.

But the Oxford team did not have time to go through this process. Getting disparate groups of scientists, doctors, drug-makers, ethicists and regulators in several countries to agree and sign off a fast-tracked trial presented massive challenges. The US Food and Drug Administration (FDA) had to grant the drug an export licence. Oxford University and the Liberian government’s drug regulatory authority had to give their approval. Their expert panels had to review all the evidence on the action and effects of the drug. Separate ethics advisory boards had to hold inquiries to decide whether the trial could meet the same high standards that are required in everyday settings in the west, including obtaining informed consent from very sick patients in rural African settings. The World Health Organisation also had to give an opinion.

The scientists’ route, which had been planned by Médecins Sans Frontières (MSF), would take them to each of the tented treatment centres staffed by MSF’s volunteer doctors and nurses, who had been running Ebola units in west Africa almost unaided since March and were the acknowledged experts in the disease.

The first stop was Donka, a collection of tents in the grounds of the national teaching hospital in Conakry, Guinea’s capital city. It had been set up to deal with the overflow of patients from the hospital’s isolation ward when the Ebola outbreak was confirmed there in March. When Horby’s team arrived on 16 October, MSF was dealing with a dramatic increase in Ebola cases. On October 6, Donka had admitted 22 patients in a single day, bringing the numbers in the 60-bed centre to 62 and forcing MSF to draw up plans to enlarge it so that they would not have to turn sick people away. Donka certainly had enough patients for a trial, but the site was ramshackle, the tented wards with timber frames had been constructed around some of the hospital’s derelict buildings.

Facebook Twitter Pinterest Health workers burning used protection gear at the Médecins Sans Frontières Ebola centre in Conakry, Guinea. Photograph: Cellou Binani/AFP/Getty Images

The three scientists, who worked at Oxford University’s Centre for Tropical Medicine and Global Health, had not encountered Ebola before. In August, Horby had returned to Oxford from Vietnam, assuming that other scientists would be urgently planning Ebola drug trials. He found he was wrong. “By September it became clear that people actually weren’t doing it. And somebody had to,” he said. “I knew we had to get into the field as soon as possible because I know from my experience that as soon as you walk in the door of a treatment unit, you understand so much more.”

MSF supplied them with personal protective equipment (PPE) – the yellow full-body suits, goggles, masks and long green gloves they needed to enter the high-risk red zone of the treatment units – and trained them to put on and later remove their suits safely while every inch was sprayed with chlorine solution.

For the scientists, the worst thing was not the fear of infection but the dehumanising effect of the suits, which made it hard to connect with scared and sick patients in the closed wards. “Most people would say initially it is a bit scary putting on PPE and going into the hot zone,” said Horby. “But how frightening it must be for the patient, especially the children, being very sick, with little family support and a bunch of foreigners in scary suits. It must be terrifying.”

Donka had patients and a good lab, but plans to dismantle the dilapidated centre and move it to a less hazardous site could have disrupted the trial. So the team moved on, flying the width of Guinea to Kissidugu town, where they and a handful of MSF staff were met by two large four-wheel drives and a pickup truck.

The convoy headed for Guéckédou, the city in the “hot triangle” where Liberia, Guinea and Sierra Leone meet. It was in this area that the virus came out of the jungle in December 2013, probably carried by a fruit bat, to infect a two year-old boy in the remote village of Meliandou.

On the journey from Kissidugu’s airstrip, the fan belt of the four-wheel drive carrying the scientists broke. In temperatures of more than 30C, the vehicle could go no further without a cooling system. As MSF’s staff radioed base to dispatch another vehicle, Merson got out and sat down cross-legged on the empty dirt road with her laptop. She was soon immersed in the detail of writing protocols for their Ebola trial.

Her colleague Jake Dunning, whose Twitter handle is @OutbreakJake, picked up the satellite phone and wandered away from the group to check in with the health and safety team at Oxford, as they had promised to do every day. He called Dr Gail Carson, an infectious diseases consultant. Excited to be using a satellite phone in the middle of the African bush, Dunning, who would lead the trial once it began, left a message. “Hi Gail – it’s Jake,” he said. Replaying it in Oxford, that was all Carson heard. The signal was poor and the rest was just garble. She tried to call him, but Dunning had switched the phone off. “All hell was let loose,” said Horby. “Jake scared the living daylights out of everybody.” Another vehicle arrived within a couple of hours, and they reached Guéckédou to find a torrent of panicked emails.

The three were originally four. Dr Piero Olliaro, 58, a specialist in tropical diseases, visiting Oxford professor and a staff member of WHO, which was supporting the trials, flew out with them but stayed only to look at the possible Guinea sites. He flew back to Geneva after a few days to work on the trial plans. When he travelled to the USA later that month for a special session on Ebola at the American Society for Tropical Medicine conference he was unable to attend: under Louisiana’s quarantine rules, he was confined to his hotel room.

After Horby, Dunning and Merson crossed the Mano river into Liberia on 20 October, they went to the northern town of Foya. The wider district of Foya was the first in the country to report cases. In early August, when MSF’s doctors arrived, the outbreak had been out of control, with 125 patients in the unit. The local people were terrified and suspicious of the foreign health workers. Dead bodies were everywhere. Foreigners in space suits were carrying them out of their homes. It was rumoured they were selling organs and that the treatment centre was a death camp where patients were killed by chlorine sprays.

The local people were terrified and suspicious. Foreigners in space suits were carrying dead bodies out of their homes

MSF’s response to the crisis in Foya became the model of how to fight the virus. The organisation’s staff sent health promoters out with the body collectors to explain why they had to take away the bodies for burial; they invited families to a visiting area where they could talk to their sick relatives at a safe distance; they designed corridors where doctors and nurses could walk without their protective gear in view of patients, and they launched radio shows giving health advice in local languages. The success of MSF’s operation in Foya meant the Oxford team arrived to find just seven patients – too few for an effective trial.

The scientists drove on to Kailahun, a large town across the border in Sierra Leone, via a red dirt road through the jungle. Sections had been washed away by the rains which deepened the mud, and there were potholes everywhere. “Because of the time pressures, we were often on the phone, or we had our laptops out in the back of the jeep,” said Dunning. MSF had set up its first centres in Kailahun in June and within the first four weeks had 90 confirmed cases of Ebola. More than 50 people had been buried in makeshift graveyards during 12 days in July, and that was just those who had died in the clinic. But the engagement of local chiefs, and the distribution of mobile phones for calling ambulances for the sick, had improved things significantly, so the scientists moved on.

Next, they headed for Bo, in the heart of Sierra Leone, to the unit the Kailahun staff had called the Palace. It had covered walkways, a corrugated roof, concrete floors, an immaculate tiled “doffing area” (where doctors could remove their protective equipment) and a gravel helipad. But again the numbers of patients were quite low. “We were constantly chasing a moving target,” Dunning told me.

The team were travelling through west Africa at extraordinary speed, yet were constantly aware of the need to move faster and get more done. The trip was often gruelling. They started out every day at 7am, visiting a new unit, donning and doffing their PPE as they went in and out of the hot zone. Dunning found he could stay in the stiflingly hot suit for up to an hour and a half; most people managed an hour at the most. In the afternoons, they visited ministries of health, meeting regulators and working out the details of the drug trial until they fell into bed at 10 or 11pm. From time to time one of them would get a hot flush and, panicking, grab for a thermometer.

On 25 October, they sped over the jungle by helicopter, to Monrovia, the capital of Liberia. Horby felt guilty for leaving the MSF workers to make the arduous trip by road, but the scientists’ business was urgent. That same day, the WHO had announced that the number of people infected had broken the 10,000 barrier.

Facebook Twitter Pinterest A woman stands by the gate of the government hospital under the rain in Kailahun, Sierra Leone. Photograph: Carl De Souza/AFP/Getty Images

The helicopter set down on a small airfield, only a short drive from the biggest Ebola treatment unit ever built. On the main airport road out of Monrovia sat a vast white-tented complex behind metal gates and a high wall, on a site originally given to American missionaries by the government in the 1950s to run a hospital, a school and a radio station, which broadcast as ELWA – Eternal Love Winning Africa.

It was there that, on 17 August, MSF opened ELWA3, the biggest Ebola treatment centre in the world. It had 120 beds, but it was soon overrun with patients. In the weeks after it opened, MSF was forced to turn away 30 people every day, taking only the sickest and most contagious. On 2 September, staff at the centre made an unprecedented appeal for western governments to send in military biohazard experts. By October, MSF had expanded ELWA3 to 250 beds and brought in more tented wards to be able to take 400 suspected cases at a time.

The Ebola outbreak in Monrovia had begun in June and the situation deteriorated quickly. In a city not long out of civil war fear and suspicion of the authorities spread as fast as the virus itself. In the first days of August, local people fought with a burial team trying to inter 22 bodies. By the end of August, corpses were being abandoned in the streets by families who did not want to be shut away in quarantine for 21 days, and then eaten by dogs.

The international response to the emergency was slow, but by the autumn, the numbers of people becoming infected in Liberia had begun to drop, and the extra capacity at ELWA3 was not being used.

When Horby, Dunning and Merson arrived at the centre on 25 October, there were 30 or 40 patients. “We could see how hard it was to manage that many patients, wearing the PPE and the heat and giving patients time – time to talk, to build that bond,” Horby told me. “We could only try to imagine what it had been like when it was full.”

In Geneva on 11 August, three days after Ebola had been officially declared a global emergency, the WHO had brought together experts for the first time to decide whether it was ethical and advisable to treat people with experimental drugs at all. Given the appalling death toll, they concluded, it was – but there was a moral responsibility to document the effects of the drugs and carry out proper clinical trials. By 5 September, the WHO had a list of the most promising drugs and vaccines. Hardly any had been tried on humans, but there had been some successful animal studies.

Over the previous few months, there had been much discussion of an experimental drug, ZMapp, which had been used to treat two American volunteers who had been infected with Ebola in Monrovia in July. Both volunteers had recovered, but without any kind of trial, nobody could be sure that ZMapp was the reason why. Their own immune systems might have fought the virus off anyway.

In late September, Horby’s team at Oxford had been among the recipients of a £3.2m grant from the Wellcome Trust to speed new drugs into trials at Ebola treatment centres. The talk was no longer of whether to trial experimental drugs in the Ebola epidemic, but which ones to choose.

The team ran through the list. Out went ZMapp, made from three monoclonal antibodies that have to be grown in genetically modified tobacco plants. When the two American volunteers were treated, there were only enough stocks in the world to treat seven people. The US government’s department of health and human services had pledged $42m (£27m) to the San Diego biotech company that made it, to speed up production and trials. But nobody knew if the drug worked and it would take months to grow enough to find out. Critically, for the Oxford researchers, the cost – rumoured to be about £65,000 for a course of treatment – was prohibitive. ZMapp would never be an option for mass use in less wealthy countries. The drug they wanted had to be easy to take, relatively cheap, easily mass-produced and with some proof of efficacy against Ebola.

One experimental drug on the list, named brincidofovir, met their requirements. They contacted a small US company called Chimerix in North Carolina to see if it was willing to supply it in sufficient quantities for the trial. “The company were amazing,” Lang told me. “We were asking an awful lot. It’s not a big company so it was quite a big ask.”

Brincidofovir was being developed to prevent and treat serious viral infections in transplant patients and others whose immune systems are damaged. But there were hopes its antiviral activity would work against Ebola too and, since it could be taken as a daily pill, it had the advantage of simplicity. The drug had been given to Thomas Duncan – a Liberian man who was turned away from a Texas hospital with Ebola and later admitted – but too late. Duncan died, however Ashoka Mukpo, a freelance cameraman for NBC News who became infected in Liberia, was also given brincidofovir and he survived.

On 20 October, Trudie Lang, 40, professor of global health research at Oxford, who was part of Horby’s team, had attended a meeting in Geneva called by the WHO to decide what Ebola drug trials would be possible and ethical. The FDA was advocating randomised controlled trials, comparing the survival rate of patients given the new drug with that of others who were not. Lang argued fiercely that the Ebola death rate was so high that to deprive any patient of a drug that might possibly work would be unethical. How would you explain to families why some patients would get a drug and others would not? “We have had health workers murdered during the Ebola outbreak. There is very fragile trust in the health systems,” she said. Instead of comparing people given the drug with others who had received no treatment, the Oxford team opted to compare death rates during the trial with those before it had begun.

Lang had started her career with the British drug company GlaxoSmithKline but now, employed by the Centre for Tropical Medicine and Global Health, she spent her life helping scientists and doctors in the developing world set up research trials. She had been infuriated by the hype about ZMapp. “People are coming back from Africa and they are being given these mysterious experimental drugs but we’re not learning anything from this kind of compassionate use,” she told me when I met her in Oxford in December.

Lang talked fast. She seemed to do everything at maximum speed, aware of the extreme urgency of the situation. “It usually takes a year to 18 months to set up a study, and usually epidemics have come and gone in 18 months, so there are never trials within an epidemic,” said Lang. “But what we’ve been able to do with Ebola – because everybody is stepping up to the mark and being incredible – we’re doing everything in parallel. We’re still writing the protocol, we’re filling out the ethics application forms, we’re sorting out the drug supply, we’re sorting out the sites all in one line.”

While her colleagues were in Africa, Lang was hitting the phones, urging regulators and the drug company to move faster. She had drawn up a strategy. It was no more than a large sheet of white paper with felt-pen scribbles in different colours, stick men and exclamation marks, but it was all there – the endpoints the trial had to meet, how to manage consent, obtaining approval for use of the drug, the possibility of side-effects.

“So we’re working really hard thinking about all the complications of the design and the statistics and getting the drug right, all the logistics and legal stuff and the regulatory hurdles. But everything we’re trying to do is make it as simple as possible inside that treatment tent because that’s the frontline,” said Lang. “We’ve got to think how we can make it as easy as possible but we’re still tasked with asking, ‘Does the drug work, is it safe, could it do more harm?’ Our job is to try to write a protocol to answer that question and then to try to make the protocol run in such a way that we can try to answer that question accurately, ethically, safely but not overburden the staff. We’re not going to do anything to a lesser standard – that’s really important.”

By the end of their two-week race across west Africa, Horby, Dunning and Merson had decided upon their trial site. ELWA3 in the Liberian capital was big, well equipped and staffed, and if the numbers of new cases were slipping, there was still every possibility they would rise again in the densely populated city.

The team, including Lang, had already chosen the best drug to trial. So now they needed to get the necessary permissions before the epidemic shifted elsewhere. In their race against time, getting the paperwork completed seemed to take forever. Dunning and his team flew back to Monrovia in November, but were stuck working on approvals and protocols, rather than enrolling patients.

On 8 December, the day the team had hoped to start the trial, I came across Dunning and one of the clinical trial nurses on his team as they crossed the yard of the spacious villa that was MSF’s Monrovia headquarters. Instead of medical gear, the nurse was carrying a large briefcase and they were heading for the government offices. “Today we’re going to try to expedite regulatory approval for the drug,” said Dunning wrily.

Facebook Twitter Pinterest Trudie Lang’s drug trial plan. Photograph: Jake Dunning

His frustration was clear. When I visited, ELWA3 was already looking quiet. Between three and six new patients now arrived each day. The triage team – nurses dressed in “light” protective clothing – were sitting in the relative cool of the first tent, where those who feared they may have Ebola were brought when they arrived. There were three of them, chatting and passing the time.

The contracts between Oxford University, Chimerix and MSF were finally signed less than a week before Christmas and there followed a race to get the drug shipped from the US just as everything was closing down for the holidays. The plan had been to get it flown to the UK and then out through Foreign Office channels to Sierra Leone. That, they now realised, would take too long, but Lang had been briefing White House officials. Just before the holiday shutdown, she was told they could have a US military airlift. The drugs were transported by road from Chimerix in North Carolina to New Jersey and then flown direct to Monrovia, landing on a military airstrip outside the city.

On New Year’s Day, the trial officially opened, but the team of six research staff, led by Dunning, were not sure what would happen. The numbers of new patients arriving had been diminishing from day to day and they were not certain they would see any new cases at all. The doctors, nurses and hygiene staff, some of them international volunteers but the vast majority Liberians, went about their normal duties, treating the 13 patients already on the ward, who were not eligible for the trial (the protocol stipulated new patients only).

The next day, a new patient was admitted, to the great excitement, but also the trepidation of the team, who had no idea whether anybody would agree to take part. There was a tense wait. The drugs had to be given within 24 hours of admission to the unit to comply with the trial protocol and to give the patient the best chance of recovery. But the patient had first to be tested for the virus by MSF’s medical staff, be told his result, then have counselling to cope with the traumatic diagnosis.

Eventually the trial team was given the go-ahead by the doctors. It was a big moment. Aware of the historic significance of what they were about to do, the half-dozen members of the team drew straws to decide who would approach the very first patient they hoped to enrol. It fell to Julia García Gozalbes, a young family and emergency medicine doctor from Spain, to seek his consent to take part in the trial.

Because the patient was still well enough to stand, Gozalbes was able to talk to him across the two rows of wire fences, so he could see her face as she explained what the trial was and the possibility that the drug might help but also that it might not. He agreed to give it a try. The rest of the team, clad in their protective suits, hugged her joyfully. Then she went in, with a local nurse, to get his signature.

A few more new patients arrived the next day and were enrolled in the trial, but they were hugely outnumbered by the staff. The team would need at least 100 patients to be dosed before they could see whether the drugs were making a difference. It became clear that it might be months before they got that number.

Outside the treatment tent, but in the red danger zone where staff had to wear protective gear, was a wooden post with clips attached. It was an ingenious solution to a tricky problem. The scientists needed to collect data on the patient’s state of health, the timing and dose of the drug he had taken, and its effects. But nothing could be removed from the red zone. A scanner was installed inside the red zone to send data to the researchers’ computers, but in the 30C heat and 75% humidity, the team worried that the scanner could break down. One option was to shout the results over the fences, but that could introduce mistakes. The wooden post served as a mount on to which the research notes could be clipped, facing the green zone, where a digital camera mounted on a wall could be used to photograph the notes.

Dunning’s team were able to see the first patients enrolled and dosed before they had to fly home on 17 January. Nobody was allowed to stay more than six weeks for fear of losing “that paranoid edge”, in Dunning’s words. Complacency could lead to risky behaviour. As soon as one team of six flew out to Liberia, the next team back in the UK began training.

Nobody was allowed to stay more than six weeks for fear of losing ‘that paranoid edge’

There were so few patients at ELWA3 that as the trial started, Dunning was already looking for another Liberian site. Before he had time to find one, Chimerix took matters into its own hands. After discussions with the FDA, it decided the numbers of people involved in the trial were too low to give a verdict on whether brincidofovir worked against Ebola virus or not and pulled the plug. Chimerix felt that the trial was unlikely to provide the evidence of efficacy that the drug company would need to win a marketing licence from the FDA. It would send no more of their drug to Liberia. On 3 February, the Wellcome Trust made the official announcement: the trial was over.

If Horby was disappointed, he did not show it. “This is the first time that we’ve really gone hell for leather to try to set a trial up during an acute epidemic and it’s been the mother of all epidemics really,” he told me. “So it’s certainly been a baptism of fire for everyone.”

Dunning also seemed pleased with developments over recent months. The drop in the numbers of people getting sick and dying was good news. “All of us would rather that the outbreak is over and we just accept that we tried – and actually we succeeded. We launched a trial. It’s never been done in an outbreak.” The trial at ELWA3 had set a precedent, so that when the next outbreak comes there will be a blueprint for how to conduct drugs trials.

Horby’s main regret is that the team didn’t get going faster. “Even though we tried to break every record to get the trials started, to be honest, it was still too late. We could have compressed some parts of the process, but the only way to make a bigger difference would have been to have started earlier.”

Recently, Dunning and Horby switched their attentions to Sierra Leone, where there were 76 new cases in the week ending 8 February, compared with three in Liberia. There are now some 200 drugs on the WHO list of potential treatments. The Oxford team chose TKM-Ebola, made by Tekmira, a Canadian company. Their drug gave 100% protection from Ebola virus in monkeys and had even been through safety trials in healthy human volunteers. On 15 February, Dunning flew out to Sierra Leone to run the TKM trial. The race is on again.

Follow the Long Read on Twitter: @gdnlongread