Science will never be the same after Covid-19

Science will never be the same after Covid-19
Image: Caleb Boyles for Quartz
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Scientists, like the rest of us, have abruptly abandoned their plans in the face of coronavirus. Genetically modified mice have enjoyed a rare break from scientific scrutiny, while new vaccines for everything from lung cancer to malaria are now on hold. The urgency of the pandemic has pushed many institutions to cast aside their established priorities, discarding samples and redirecting manufacturing plants in the rush to reallocate resources. Coronavirus has subsumed their work.

Quartz spoke with four major research institutions in Germany, Nigeria, Israel and the UK to highlight how scientists are pivoting to focus on Covid-19. For some, the switch to coronavirus is obvious: Vaccine-creating immunologists have invaluable knowledge that can be used to fight the disease. Others have put their locked-down labs to good use, repurposing them for coronavirus-related work far outside their usual area of expertise.

All four teams have made huge sacrifices as they’ve redirected their efforts. Dozens of promising studies and treatments were halted on the cusp of completion, and many must wait until after the pandemic to be finalized. The dramatic drop in non-coronavirus research will inevitably slow important discoveries.

As well as facing scientific challenges, the researchers must navigate unusual practical difficulties. Some have hired catering teams to support researchers working through the night, while those who need to fly biological specimens across closed borders face even more bureaucracy than usual.

Science has never before been redeployed and advanced at such a rapid pace. Researchers accustomed to plodding their way through research proposals, meticulous grant applications, and journal reviews have discovered they can mobilize and switch focus at high speed. They have picked up new skills, developed pandemic protocols, and upended their schedules. These laboratories are unlikely to fully revert to old habits now that these abilities have been unleashed. Scientists are learning to pivot, fast.

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Germany: Max Planck Institute of Experimental Medicine

In early March, Nils Brose ran into an acquaintance in the supermarket. The director of the Max Planck Institute of Experimental Medicine in Germany was stocking up on wine to see him through lockdown when he started chatting with a doctor at Göttingen University Medical School, who was building up his own wine supplies.

It turned out the doctor was helping to plan coronavirus diagnostics for the city of Göttingen. “If you need support, I think we could redirect our lab,” offered Brose. His usual work had stopped, with scientists sheltering at home as the virus swept Europe. Their lab equipment might be useful.

It was the beginning of a pivot that led to a very different type of work for Brose and his colleagues, and successfully created a diagnostic testing center. The Max Planck Institute of Experimental Medicine is typically dedicated to studying mice brains. Brose and his colleagues manipulate synapses, the junctions between neurons, to uncover the functions of specific genes. “We generate mouse mutants,” says Brose. “It has nothing to do with coronavirus testing.”

But the lab is one of the most sophisticated mouse genetics research sites in northern Germany. Every time the lab mice reproduce, their offspring must be characterized to see whether or not they carry their parents’ mutations. Scientists do this using the polymerase chain reaction (PCR) method, which amplifies DNA sequences—the same technique used to detect the presence of coronavirus genetic material in diagnostic testing.

Fritz Benseler, whose lab at Max Planck had several PCR machines used for mouse genotyping, quickly began speaking with Göttingen University researchers to figure out what was needed. The institute had already begun developing coronavirus diagnostic tests in March, with plans to use them on their own staff. Though they had enough PCR equipment, they needed to restock on swabs and RNA-protecting buffers. It took four weeks to fully adapt the lab for diagnostic testing. Once they were up and running, it took another week of testing to ensure the lab gave similarly accurate results to other testing centers in the area.

The institute processed its first coronavirus test in mid-April, around six weeks after Brose first suggested it in the local supermarket. Since then, it has tested several hundred people for coronavirus. This relatively small number is a reflection of the low rate of contagion in the area; there were 1,164 cases and 78 deaths across the Göttingen region, which has 253,000 inhabitants, as of June 10. Brose said his lab had the capacity to test a thousand people a week, but only saw around 50 to 80 a week.

Despite the low number of cases, the new testing abilities are essential to helping the city reopen safely. This principle was put to the test by a series of private parties in Göttingen in May, which led to a spike in cases in June; 166 people were quickly tested, of whom 68 had the virus. Three hundred more were found to have come into close contact with the coronavirus patients and were ordered to quarantine for two weeks. Göttingen had the capacity to quickly test this surge in patients, allowing scientists to monitor and hopefully contain the outbreak.

In May, the institution also started putting its skills to use testing its own staff. The research Brose and his colleagues do on mice is essential to understand the brain synapse malfunctions that cause many psychiatric diseases in humans. There are 150 scientists at the institute, of whom 80% were off work from mid-March until the end of May. Brose says that within his own lab of 25 scientists, at least 20 different research projects were delayed. As the lab re-opened, testing the institute’s own scientists who were returning from abroad or had contact with possible infected people allowed them to avoid unnecessary quarantines. On June 11, Brose and his colleagues tested two full departments, making up 70 people, at the institute. And they’re planning to set up saliva-based testing to regularly check personnel.

Though usual projects are resuming, the Max Planck Institute of Experimental Medicine doesn’t plan to put aside its coronavirus work entirely. Germany is aiming to ramp up its trace-testing capabilities, whereby those who inadvertently come into contact with coronavirus patients are identified and scheduled for testing. Brose says this systematic large-scale testing approach could help avoid another lockdown. The institute’s coronavirus testing lab could be further automated to increase its capacity to a thousand samples per day, says Brose. This way, he says, Göttingen will be prepared for the next wave: “This isn’t going to be the last corona pandemic.”

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Nigeria: African Center of Excellence for Genomics of Infectious Diseases 

For scientists in Nigeria, coronavirus wasn’t the first epidemic of the year. When Covid-19 arrived in February, the country was in the midst of tackling a Lassa fever outbreak. Cases of the disease, which can cause fatal hemorrhagic symptoms, were at the highest numbers ever recorded, and Nigeria was also beset with a malaria outbreak.

Scientists at the African Center of Excellence for Genomics of Infectious Diseases at Redeemer’s University were researching both Lassa fever and malaria when the country’s first Covid-19 case was recorded on February 27. “We immediately stopped what we were doing,” says Christian Happi, director of the institute. “We re-organized the lab.”

At the time, the Center was working to create a rapid diagnostic kit that would test for malaria, Lassa fever, and Ebola all at once. A high temperature is a symptom for all three diseases, and a combined test would allow those with a fever to go to one testing center rather than several different places. But the project was put on hold as scientists focused on processing diagnostic tests for Covid-19.

Across the Center, nearly everyone within the team of 100 scientists redirected their efforts to coronavirus testing and sequencing by early March. Researchers working to collect samples from patients with Lassa fever were able to push on for another two weeks but, by mid-March, they too had to stop. Pausing this work was particularly difficult, says Happi. Researchers will likely have to re-collect fresh samples of the virus when they resume their work on Lassa fever.

By March 3, Happi and his colleagues were working to sequence the SARS-CoV-2 genome. Like other viruses, the one that causes Covid-19 slowly mutates over time, so it tends to be different depending on where it’s travelled from and through. Happi and his colleagues sequenced the genome of the coronavirus in Nigeria, and found that it seemed to have travelled from China via Italy. This work is necessary to understand the structure, origin, and mutation of the virus, which informs what drugs and vaccines can be used to combat it. “Sequencing is critical to any counter measure,” says Happi, who also helped sequence the Ebola genome.

At the same time, the lab was the first in the country to be called upon by the government to start coronavirus diagnostic testing. Happi began ordering extra protective gear to prepare in February, and created a rotation of eight-hour shifts so that scientists were available 24 hours a day. As restaurants were closed for social distancing, Happi also hired a catering team to provide food for researchers. The Center had a government mandate to turn around diagnostic tests within 24 hours, and were testing an average of 100 patients a day by May.

The Center was nearly exclusively focused on coronavirus for two months. But by early May, its researchers faced immense pressure to pivot back, and pick up some of their previous work addressing Lassa fever and malaria. Onikepe Folarin, a geneticist at the Center, believes cases of both diseases will surge as a result of scientists pausing their work for the sake of coronavirus. National attention is still strongly focused on coronavirus testing, and Folarin worries that people will be less conscious of the need to be tested for malaria. “No one’s paying attention to them [malaria and Lassa fever] because Covid is on and everything is focused in that direction,” she says.

The Center is still working on coronavirus testing and sequencing but, rather than devoting the entire workforce to this effort, some scientists re-started work on other infectious diseases in May. As an institute working to combat already under-studied and under-funded endemic diseases like malaria, the Center can’t afford to pivot as hard or for as long as some other global research centers.

Scientists need to understand how coronavirus interacts with other conditions, such as malaria, says Folarin, as this could affect testing and treatment. Initially, she says, it made sense to focus only on coronavirus, with the hope that it could be quickly contained. But given that coronavirus will be around for months longer, if not years, they can’t afford to neglect their other work. “As we go on, it’s looking like it won’t be contained within a short period of time,” she says. “We can’t ignore other diseases for the sake of Covid.”

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Israel: Migal Galilee Research Institute

Scientists at Migal Galilee Research Institute are fortunate to be in a very different position from those at the African Center of Excellence for Genomics of Infectious Diseases: Rather than trying to study multiple deadly diseases, they have been devoted to researching coronavirus for the past four years. Chicken coronavirus, that is.

Infectious bronchitis virus (IBV), a form of coronavirus that affects poultry, has been ravaging livestock in Israel for the past 15 years. In 2016, the Israeli government tasked the Migal Institute with developing a new vaccine; the disease had mutated so much that it no longer responded to existing vaccines.

Given the quickly-mutating nature of the virus, a team of five scientists at Migal decided to focus on creating a so-called subunit vaccine. Traditional vaccines inject an inactivated virus into the body, prompting the immune system to produce antibodies in response. But scientists at Migal worked to identify a few key proteins within the virus that could elicit an autoimmune response; rather than injecting the whole virus, they would inject just those proteins. “If there was a shift in the virus, this vaccine would be easy to adapt—like we do every year with influenza,” says Itamar Shalit, a Migal board member and infectious disease physician advising on the team’s Covid-19 vaccine.

Migal scientists created a vaccine using three IBV proteins and, in December, successfully showed it protected chickens against disease. Two weeks later, SARS-CoV-2 started sweeping the planet. “Coincidence is key in life,” says Shalit. In early January, the institute’s researchers paused their work producing and distributing the new IBV vaccine to poultry businesses, and instead started to apply their knowledge to creating a vaccine for Covid-19.

First they examined the structure of Covid-19. The virus is built out of several proteins, including nucleocapsid (N) proteins that form a shell around the genome, protecting it from the immune system, and spikes (S proteins), which stick out of the N-protein shell and grab hold of receptor molecules to spread the infection.

To start work on their vaccine, the scientists needed to bring these essential proteins to their lab, which required flying them in from abroad. “This was a nightmare,” says Shalit, especially as many borders were shut down worldwide. “It was a military operation to bring these things together so we have them in northern Israel.”

Once they had the necessary biological materials, the five scientists who had created the chicken vaccine worked to translate their efforts into a vaccine for humans. They created a vaccine using an S protein and two N proteins, rather than the virus as a whole. Scientists then genetically modified bacteria to produce the required proteins in a liquid secretion, which was purified to create the vaccine. By the end of May, they were ready to test their vaccine on mice and rats.

The Migal scientists, like so many others worldwide, are working at a frantic pace with the goal of creating a coronavirus vaccine by 2021. Shalit is over 70 years old and used to be head of a major hospital. “I’ve never worked so hard before,” he says.

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The United Kingdom: Jenner Institute 

Oxford University is the only academic institution in the UK with its own vaccine production facility. In late February, the university’s Jenner Institute, housed in its medicine department, made the remarkable decision to stop ongoing manufacturing and switch to producing a potential coronavirus vaccine. The move was part of a massive pivot, as scientists working on more than 15 diseases, including MERS, HIV, Ebola, Zika, malaria, lung cancer, and prostate cancer, dropped their work to focus on coronavirus.

The institute’s coronavirus research first began on a smaller scale at the very beginning of 2020. Vaccinologist Sarah Gilbert and her team started studying the virus as soon as China released its first genetic sequence on Jan. 12. More resources were gradually added to the effort, until, by the end of February, it was clear a bigger redeployment was necessary.

The decision to stop vaccine production was not taken lightly, says Adrian Hill, director of the institute. The vaccine production factory is highly sought after, and scientists have to book its use at least six months in advance. Some of the vaccines midway through production were frozen for use after the pandemic, but many of them had to be thrown away. “Viruses grow on living cells,” says Hill. “These cells have to grow in a certain environment, to a particular density, before they can be infected.” It’s delicate work, and pausing means much of it must be destroyed.

The Jenner Institute also stopped many of its clinical trials. Vaccine trials typically involve hundreds, if not thousands, of participants who are monitored over many months, and this delay disrupted those carefully-orchestrated plans. Only a few appointments, where blood tests were necessary to check for potentially dangerous side effects, were held in person. Some follow-up monitoring switched to Zoom, but at least a dozen trials were put on pause.

Challenge trials for malaria, in which participants are deliberately infected with the disease and monitored for ill effects, were among the stopped studies. These participants have to set aside a month of their life to be carefully monitored, as they often need intense medical treatment if the vaccine candidate is ineffective. It’s unlikely all these participants will be able to rearrange that commitment whenever the trial is rescheduled. “That’s pretty disruptive,” says Hill.

Across the institute, more than 200 scientists who work in many different roles have redeployed their efforts to work on the fast-tracked Covid-19 vaccine. Though every other project has shut down, Hill says fewer than 50 people have nothing to do. “Most found something to usefully contribute,” he says.

They were able to pivot so quickly in part because Hill and his colleagues had been planning for a pandemic for several years. Gilbert had been working on a template for how the institute could quickly mass produce a vaccine if needed. When Covid-19 started sweeping the world, she started work on a vaccine based on an adenovirus: By genetically engineering the genome of a virus that causes mild cold-like symptoms, it instead mimics the virus that causes Covid-19. When used as a vaccine, this adenovirus then prompts the immune system to fight coronavirus.

Thanks to this work, the Jenner Institute is currently running the most advanced coronavirus vaccine trial worldwide. In March, scientists injected their vaccine into six rhesus macaque monkeys at National Institutes of Health’s Rocky Mountain Laboratory in Montana, and exposed the monkeys to large volumes of Covid-19. All six remained healthy.

Scientists then launched a massive phase one trial of human participants in April. Most phase one trials, which evaluate vaccine safety, typically involve a few dozen participants, but the Jenner Institute’s includes 1,050 participants. Before the full results had been analyzed, a combined phase two and three trial with more than 6,000 participants began in May. The institute is supporting coronavirus trial sites in North America, Africa, and Asia, as well as in the UK.

The logistics of organizing such a huge international trial, and at warp speed, are immense. In non-coronavirus times, if scientists managed to launch a trial abroad after a year of planning, “you’d be doing really well,” says Hill. To focus their current work, senior investigators at the Jenner Institute divided up the project into immunology, manufacturing, clinical trials, and managing partnerships with other companies and institutions. Hill took the lead in arranging partnerships, which he said was logistically challenging as the institute re-configured itself.

Despite those challenges, Hill says the chance to produce a coronavirus vaccine is in some ways simpler than the institute’s usual work. “The easy vaccines have all been made. There aren’t many diseases left where you could make a vaccine and in six months, it would still work,” he says. Most diseases without a vaccine, such as HIV, mutate so rapidly that vaccines are soon rendered useless. Early sequencing shows that Covid-19 does mutate, but seems to develop and change at a reasonable rate. It’s possible—though far from certain—a single vaccine could be effective. “Covid is an unusual opportunity to make a vaccine that might be easy,” says Hill.