In labs around the world, researchers are furiously working on ways to tackle the COVID-19 pandemic. Therapies to treat the symptoms, antivirals to combat the novel coronavirus itself, and ultimately vaccines to defend the public from the fast-spreading bug.
Some labs have been preparing for years. At the world’s most secure facilities—Level 4 laboratories like the Canadian lab in Winnipeg—pandemic preparedness has long been a key part of their work.
There’s reason to be optimistic. The Winnipeg lab has been on the cutting edge of infectious disease before. At that lab a decade ago, one brilliant researcher came up with a new strategy to fight the Ebola virus. It was a medical breakthrough that, based on some cases, brought infected patients back from death’s door. It is research that, today, could unlock the secret to beating COVID-19—and other viruses including HIV.
Canada was in a unique position to stop what was, at that point, one of the worst epidemics in modern times—before bureaucracy and government stinginess got in the way. Back then, plans were drawn up and budgets written to treat 5,000 patients in Ebola-stricken West Africa, and that was just the beginning. With some luck, Canada could help save tens of thousands more. And it could have the knock-on effect of breathing life into its biotechnology sector to help prepare for the next epidemic.
But the plans fell apart.
As shown in hundreds of pages of government documents obtained through Freedom of Information requests, the machinery of government crushed those well-intentioned plans. Interviews with those involved explain how bureaucratic infighting, tight budgets, and a partnership with a private tobacco company all contributed to Canada’s inability to get this life-saving treatment to those who needed it.
The genius researcher who pioneered the treatment would go on to focus on other things, including strains of coronaviruses. Last year, she was led out of the lab, escorted by the federal police as part of a secretive investigation about which the government remains mum. She is now the unfortunate target of international conspiracy theories.
As the world puts its shoulder to the wheel in search of a cure for COVID-19, the story of how Canada failed to fight Ebola serves as a cautionary tale as to what can go wrong.
Around 2008 at the National Microbiology Laboratory in Winnipeg, Xiangguo Qiu was nearing a breakthrough. Like many Chinese scientists looking to further their work, Qiu—who was from Tianjin, China— had moved to Canada in 1996. She joined the Winnipeg lab in 2003, just a few years after it opened. Working in the special pathogens unit, Qiu’s job was to identify emergent viruses that could lead to epidemics, even pandemics. In the mid-2000s, Qiu turned to the Ebola virus, even though it hadn’t been seen on a large scale since its discovery in 1976.
Qiu spent years designing a cure for a virus that, by and large, hadn’t been seen in humans in decades. She began investigating a therapy, whereby she would flood the patient’s system with antibodies. Even if it sounds simple, that solution was not intuitive. Antibodies are Y-shaped proteins that are produced naturally by the body—they work by latching on to invading viruses and bacteria, flagging them for the white blood cells to attack. But what makes Ebola so deadly is its ability to kill those white blood cells, kneecapping the immune system’s response. Other researchers were far from convinced: If the white blood cells couldn’t respond effectively, what good were the antibodies?
“The conclusion was mainly that antibodies would never work against Ebola,” said Gary Kobinger, one of Canada’s most celebrated infectious disease experts who served as the chief of special pathogens for the lab until 2015. In an interview with Foreign Policy, he recalled that Qiu “kept pushing.”
Around that time, Canada’s then-Conservative Party government reduced the lab’s core funding by about a third.
“I had to stop a lot of projects and put them on ice because we just didn’t have money,” Kobinger said.
In the post-9/11 world, governments around the world had found themselves woefully unprepared for the possibility of an easy-to-carry-out chemical or biological attack. Labs worldwide were researching how to prevent outbreaks and stop the spread of deadly viruses.
In America, defense dollars flowed fast. The Biomedical Advanced Research and Development Authority was set up to help fund the research and development of countermeasures to viruses and pathogens that could be used in bioterrorism. At the end of the R&D process, there was the promise that the Pentagon might buy huge quantities of the treatment or vaccine for its national stockpile. It meant that labs could pioneer cures that might not have any short-term commercial application, but thanks to their clear nexus to national security, could still come out with a profit.
In Canada, researchers weren’t quite as lucky. Ottawa is significantly less liberal with its research funding than Washington, and there is not the same promise of government contracts for innovative firms. Especially at that time, under a tight-fisted conservative government, there was a tremendous push to develop medical advances that could be commercialized and offloaded from the government quickly. Qiu learned that well.
“I sat down with Qiu and said, ‘Listen, I might be the only one, but I believe in your antibodies,’ ” Kobinger told Foreign Policy. So the lab trials continued.
Qiu was right. Her research showed that if enough of these antibodies were introduced, they would glob on to and weigh down the virus, even blocking it from entering healthy cells. That gave the white blood cells a fighting chance to take down the invaders. It’s like an exploding dye pack in a bag of stolen money—not only does it identify a bank robber, but it may actually slow their getaway.
Economic necessity became the mother of new invention at the lab. While there was a long list of different antibodies that could be used as a therapy, Kobinger pushed Qiu to identify only the three most effective ones for future research. They called the result ZMAb—short for the three EBOV-GP-specific monoclonal antibodies—and they patented the treatment in 2009, uploading the details of the cure on publicly available American and Canadian patent databases.
In clinical trials on various animals, ZMAb showed remarkable promise. In one study, published in the journal Nature, the lab announced that taking the three antibodies would lead to “complete survival when administered at 24 hours post-infection” and would still be effective at fighting the virus as late as five days after symptoms began. But, as there had been no major outbreaks of Ebola in years — to that point, there had been only small outbreaks in West Africa, killing about 300 people a year — clinical trials in humans weren’t an option.
ZMAb would sit on a shelf. Just in case.
On Aug. 8, 2014, the World Health Organization declared a public health emergency in West Africa. Ebola had spread quickly through rural areas of Guinea and had reached major cities in Liberia and Sierra Leone. It was already the worst outbreak of the virus ever recorded, with nearly 1,000 deaths, and it was only beginning.
At the Public Health Agency of Canada (PHAC), officials were eager to confront the emerging outbreak.
“There is rapidly increasing high level interest in all matters pertaining to Ebola situation,” wrote Assistant Deputy Health Minister Rainer Engelhardt in an email obtained under Canada’s freedom of information laws.
In the years since Kobinger and Qiu patented their Ebola treatment a year after discovery, Canada had actually sold the licensing rights to ZMAb to Toronto biodefense company Defyrus, which wasn’t uncommon. The lab had limited capacity to bring ZMAb to market, so it made sense to open its development to the private sector. If an outbreak occurred and an emergency was declared, however, Canada always had the right to produce ZMAb on a noncommercial, or “compassionate use,” basis.
The nuts and bolts of Qiu’s innovative treatment were readily available online—the lab had published papers about ZMAb’s promise. In the early days of the 2014 outbreak, PHAC got a phone call from California-based Mapp Biopharmaceutical. The company had come up with its own antibody cocktail and wanted to collaborate. It had, in fact, already struck a sublicensing deal with Defyrus.
The Winnipeg lab saw no problem with that. In a way, both sides were on the same team. “For me, it’s not about my antibody, your antibody, I don’t care—what I want is the best treatment,” Kobinger said. It helped that Mapp Bio had significant grants from the U.S. government.
The National Microbiology Laboratory tested Mapp Bio’s treatment and found that one of its antibodies worked better than one of Qiu’s. The lab mixed the two Canadian antibodies with the one discovered in America and called the result ZMapp.
Getting private industry and government health agencies to work together should have been the hard part. But with the crisis in full flow, everyone at the table seemed keen to get started.
“PHAC came with all their big enthusiasm,” Kobinger recalled, “and said, ‘We need to make this in Canada. And we need to use this as a way to build capacity in Canada.’ ”
But Canada had little ability to mass-produce antibodies like the ones needed for ZMapp.
To make ZMapp, they would need a cell line—a culture, usually made up of Chinese hamster ovary cells, that would be used to replicate the antibodies in large quantities. Chinese hamsters have been the foundation of molecular biology for most of the past century. Researchers discovered around 1919 that they reproduce quickly; their immune system is very receptive to foreign pathogens and parasites; and they have relatively few chromosomes, making their genetics easier to understand. The only real downside is that they resist breeding in captivity. By the late 1950s, scientists discovered that an ovary cell from a female hamster could be quickly and efficiently cloned, and each could be used to replicate a chosen protein. In these rows of hamster cells, scientists had essentially created tiny biological factories. Cell lines.
The promise was endless. So much so that H.C. Hu, a Chinese researcher, smuggled out a small crate of hamsters as Mao Zedong’s forces approached Peking. He handed off the tiny rodents to Robert Briggs Watson, an American researcher studying a cure for malaria.
But even from those noble beginnings, there were fears that these cells could be used to nefarious ends. After Watson and H.C. Hu smuggled the rodents out of China to New York, they were accused by a germ warfare commission set up by the People’s Republic of China of war crimes and plotting a biological attack, resulting in H.C. Hu being sent to a “reeducation” detention camp. While the wild accusations were part of the Maoist paranoia of the 1950s in China,
In Canada, there is really only one Chinese hamster ovary cell line available, and it belongs to the National Research Council (NRC), a government agency with a mandate to “take research impacts from the lab to the marketplace.”
“So who got involved?” Kobinger said. “NRC.”
It should have been straight-forward: PHAC had the treatment, NRC had the cell line. Together, they should have been able to mass-produce the antibodies needed.
Instead, the bureaucratic wrangling began almost immediately. In late September 2014, NRC invoiced PHAC nearly $200,000 for its “services”—before any antibodies were even grown.
The NRC decided it was responsible for ZMapp and began running the show, Kobinger said. “They [NRC] were holding their cell line saying, no, you can’t have access to it.”
The NRC saw an opportunity to commercialize ZMapp. There were millions of dollars in grants available to whoever would be able to mass-produce it. That money wouldn’t come from shipping the treatment to Africa, however.
Meanwhile, the U.S. Biomedical Advanced Research and Development Authority “calls me and says, ‘Gary, I don’t understand, there’s these people at NRC who are telling us that these antibodies are theirs,” Kobinger recalled. “ ‘And we know they are developed by you. What they are telling us is that we’re going to develop these monoclonal antibodies in [Chinese hamster ovary] cells and you’re going to pay for it.’” Kobinger said he received a similar call from the Gates Foundation.
While the NRC, in emails to Foreign Policy, downplayed its involvement in the production of ZMapp, those involved say the agency was hungry to pass off this project to the better-financed Americans. But there was a big problem with that.
Mapp Bio, much like the Winnipeg lab, focused on diseases “where commercial markets are minimal,” Larry Zeitlin, president of Mapp Bio, told Foreign Policy. His company relies on grants, he explained, and U.S. agencies look for one key thing: “Innovation,” he said.
Mapp Bio wanted to do away with using Chinese hamster ovary cells to grow the antibodies. Plant cells, it hoped, would be faster and cheaper—specifically, tobacco plants.
The motivations weren’t hard to identify. So Mapp Bio partnered with Kentucky BioProcessing, which had earlier that year been acquired by Reynolds American, one of the largest cigarette companies in the world.
“At the time, we were told, or there was evidence that, tobacco plants were actually faster and more effective,” said Greg Taylor, who served as Canada’s chief medical officer and head of the PHAC from 2014 to 2016. “That’s why we were interested.”
It was all hypothetical, however. Zeitlin confirmed that Mapp Bio had never brought a product to market using tobacco cells. While there is ample research on the promise of plant cells for this sort of production, regulators had not approved any drugs or therapies grown in plant cells. ZMapp would be their trial run.
The move was a public relations coup for the tobacco giant. ZMapp was a case study as to “How Big Tobacco and the Military Came Together,” as NBC News heralded it on Aug. 5, 2014, without mentioning that the treatment had been developed in Canada.
In October, a joint NRC/PHAC report was prepared. It laid out three possibilities to “fast-track production” of ZMapp.
One was to have Canada ask Mapp Bio to take over. The second was for Ottawa to produce ZMAb itself, without the Americans.
But the government opted for the third option: to find domestic producers to make two of the antibodies in Chinese hamster ovary cells and have Mapp Bio produce the third in tobacco plant cells. The cocktail would be combined in Canada and shipped to West Africa.
The report concluded that despite the insistence from the Americans, tobacco plants would be “slower than the industry standard” and would not necessarily be more effective. There was a caveat: If the Americans couldn’t produce the antibodies, PHAC would find someone to do it in Canada.
The report requested $22 million to produce the Canadian antibodies, which would be enough to treat nearly 5,000 patients. That would serve as ZMapp’s human trial. The report envisioned a “long-term, large-scale” approach, recommending an additional $38 million be spent on a second round of production that could help treat up to 36,000 people.
Hiring Canadian firms to make two of the antibodies had the knock-on effect of financing the labs’ capital costs so they could mass-produce antibodies for other applications in the future; there was already emerging interest that antibody therapy could treat a host of other infectious diseases.
The first doses would be delivered to the Ebola-afflicted regions by March 2015.
As the bureaucratic cogs turned, PHAC was already receiving requests to treat health care workers who had contracted the virus in the field. Documents show that throughout 2014, Ottawa shipped more than a dozen doses of ZMapp and ZMAb throughout the United States, Europe, and West Africa to treat sick doctors and nurses, and Mapp Bio shipped a dozen more.
In nearly every case where the treatment was used, the patient survived.
“All the clinicians who called me said, ‘We are convinced that your stuff has saved the lives of these patients,’ ” Kobinger said.
Pretty much as soon as PHAC began trying to get the plan off the ground, it fell apart.
Two medium-sized labs, one in Montreal and the other in Toronto, were tapped to produce the antibodies. At least one of the labs viewed the contract as the first step toward scaling up to produce other lifesaving treatments in the future.
But the contracts weren’t for millions after all. The NRC contracts were inexplicably just $325,000 each.
Then there was the third antibody. The Americans never seemed to get the memo. Speaking to Foreign Policy recently, Zeitlin said the plan was news to him. “I’m not sure what your information about just one antibody is referring to,” he wrote in an email.
Ottawa had successfully made a small quantity of two antibodies. But instead of forging ahead, it suddenly scuppered the plans, and no further contracts were issued to the companies. An internal report lamented that “significant investments required” and “limited financial incentives for the private sector” had stymied the project.
Conversations kept happening anyway. In November, both agencies had a call with Medicago, a Quebec City company, to discuss the “business proposal” for ZMapp. Medicago, like Mapp Bio, wanted to grow antibodies in tobacco plants; 40 percent of its company is owned by American cigarette giant Philip Morris.
That didn’t work, either. PHAC denied to Foreign Policy that it ever discussed ZMapp with the company, contradicting its own internal documents.
By the start of 2015, more than 8,000 were dead in West Africa.
In April 2015, Ottawa inked a $3 million contract with Mapp Bio for ZMapp. But the company had other orders to fill first, for the Pentagon, and it was pushed back. The final delivery date was scheduled for June 2016—the same month the outbreak officially ended, leaving more than 11,000 dead behind.
A spokesperson for PHAC, citing security reasons, refused to confirm how many doses were delivered. Mapp Bio confirmed that doses were provided to PHAC, but a nondisclosure agreement covers the contract.
Ottawa never sent more than a few dozen doses of ZMapp or ZMAb abroad.
“We were so ahead on all fronts,” Kobinger said, adding that it’s all “an unfortunate series of events.”
ZMapp had another chance, in August 2018, when a second outbreak began in the Democratic Republic of the Congo. Mapp Bio quickly produced the necessary antibodies and sent ZMapp to the affected regions, where it was included in ongoing clinical trials. Canada had no involvement in those trials.
Yet preliminary results, published in the New England Journal of Medicine, showed that just half of the patients who received ZMapp survived. That’s a far cry from the high survival rates researchers had seen before.
Zeitlin told Foreign Policy there are a few explanations for why ZMapp performed poorly. The virus in the Democratic Republic of the Congo may not have been the same as the one from Guinea. Or ZMapp may not have been as effective as researchers once hoped.
But a third theory points more blame. “Quicker infusion may be important for antibody treatments,” Zeitlin said.
Qiu’s original idea behind the antibody therapy was to flood the patient’s system. When the National Microbiology Laboratory sent doses abroad, which had been grown in the lab using Chinese hamster ovary cells, that’s how they were administered—quickly.
But doctors who had been equipped with the tobacco plant-grown ZMapp found that patients’ bodies didn’t take the plant-based treatment as well. It had to be administered more slowly, over four hours.
Mapp Bio appeared to recognize the problem even before the clinical results came in. Zeitlin said the plan had been to abandon tobacco plants and move to the Chinese hamster ovary cell production. But after ZMapp had been shown to be less effective, it was excluded from future trials.
“Further development is discontinued,” Zeitlin said.
The 2018 outbreak was officially declared over on June 25. It left more than 2,200 dead in the Democratic Republic of the Congo, primarily in the northeast. A new outbreak, in the northwest, was declared in early June.
ZMapp didn’t have to end this way.
Mapp Bio pursued the strategy it did because the nature of private-sector research required it. “When you try and actually develop things from a proactive need, public-good perspective, it’s very difficult,” said Taylor, the former PHAC head.
But there was no reason why Ottawa could not have gotten ZMapp out the door as originally planned, back in early 2015, when it was needed most.
“PHAC came out with good intentions and a good plan and good everything but got completely stalled and neutralized by the NRC,” Kobinger said. It was all because of “a few people.”
Kobinger added: “From the beginning, it was definitely a strategic mistake to have pushed so hard for tobacco plants.”
A spokesperson for the NRC insisted that there was no “push to establish a ‘business case’ to develop a plant-based production process for ZMAb.” That’s directly contradicted by memos and emails from the NRC itself, which repeatedly cite the need to find a commercial justification for the treatment.
“What needed to happen, which did not happen, is that somebody with a reasonable mind at a very high level, at the ministerial level maybe, needed to sit everyone down and say, ‘You’re crazy. This is happening. We’re trying to help the world,’ ” Kobinger said.
While ZMapp may be effectively dead, the ideas behind it live on.
Zeitlin said Mapp Bio is now pursuing a new treatment for Ebola and the similar Marburg virus. Monoclonal antibody treatments are also showing promise in fighting HIV. “That is what I’m the most excited about,” Kobinger said.
Two monoclonal antibody treatments in the Congo trials, which were developed after Qiu’s breakthrough, were shown to be effective. (Both were administered quicker than ZMapp.) The developer of one of those treatments, Regeneron, hopes to soon have a three-antibody cocktail to treat COVID-19.
There is still a push to bring big tobacco into the lab, too. In March, Kentucky BioProcessing and Reynolds American announced they are “in the process of developing a vaccine candidate [for COVID-19] that we hope to have available for testing within the next few weeks,” said Kaelan Hollon, a spokesperson for Reynolds American. British American Tobacco has made a similar announcement.
Kobinger left the Winnipeg lab in 2015. The bureaucratic infighting over ZMAb was a big driver, he said. He recalls telling Qiu at the time: “If I want to stay ahead of this curve, a little bit, and I still have a chance to contribute, I need to leave and go into academia.” Kobinger is now at Laval University’s Infectious Disease Research Centre in Quebec City. Recently, he has partnered with Medicago to develop antibodies that could help fight COVID-19.
Qiu continued working at the National Microbiology Laboratory. In 2017, she penned a prescient article with a colleague lamenting the lack of funding to research vaccines for coronaviruses.
Given the cost and time it can take, she wrote, “there is a lack of incentive from agencies to fund research into and develop vaccines against obscure pathogens that may or may not cause outbreaks in humans.”
Qiu’s work, however, was cut short. In July 2019, the Royal Canadian Mounted Police entered the Winnipeg lab and escorted her off the premises. Neither the RCMP nor the federal government will explain what Qiu is alleged to have done. She has not been charged with a crime.
Qiu had been working with the Level 4 laboratory in Wuhan, China, in the years before her removal. The Winnipeg Free Press reported that the RCMP investigation found that Qiu failed to follow protocols for how deadly viruses, including Ebola, were sent to colleagues in China. Kobinger told Foreign Policy he believes Qiu followed all appropriate protocols and that the allegations are bureaucratic in nature and overblown.
As COVID-19 began spreading in Wuhan, conspiracy theories percolated. ZeroHedge, a pseudonymous blog known to peddle Russian disinformation, alleged that Qiu gave the coronavirus to the Wuhan lab, which was weaponized by Beijing.
These theories have been debunked. Researchers say there is zero evidence the virus was made in a lab. Qiu’s life work, Kobinger said, has been to help the world battle pandemics like this.
Canada could have produced the necessary antibodies, which could have saved lives in West Africa. It could have scaled up domestic capacity to produce lifesaving treatments for infectious diseases. It could have treated its internationally renowned researchers better.
It failed across the board. African victims of Ebola paid the price. Will the handling of possible coronavirus vaccines be any better?