The Long Game of Coronavirus Research – The New Yorker

NEIDL has been working with live samples of the coronavirus since March, when it received a sample that was derived from the U.S.s first diagnosed case: a thirty-five-year-old man in Washington State who had recently returned from Wuhan. But its staff had been making plans to investigate the virus since January, when early reports of its rapid spread convinced them that it would proliferate worldwide and lead to severe outbreaks in the U.S. They immediately began writing protocols for using the virus and submitting requests for approval from B.U. In March, institutions at B.U., including NEIDL, received 1.9 million dollars in funding from the Massachusetts Consortium on Pathogen Readiness, part of a hundred-and-fifteen-million-dollar grantcordinated by the Dean of Harvard Medical School and financed by a Chinese investment fundto support researchers working in the Boston area and Guangzhou.

In the U.S., most of the B.S.L.-4 labs are in government or military facilities, but NEIDL, despite its origin as part of a federal initiative, operates on an open academic model. We work with absolute transparency, its director, Ronald Corley, told me. We have to have the trust of the public, so everything we do is known and communicated freely. In the past two years, Corley, a lanky microbiologist in his seventies, has recruited fourteen scientists to join the center, looking for researchers with a wide range of expertise. The staff of NEIDL and its affiliates includes experts in the basic biology of the deadliest pathogens, in animal models that can be used to mimic the progress of human diseases, and in effective treatments and potential vaccines. Corley believes in giving them the freedom to pursue their hunches without being micromanaged. From the outset, he organized the centers COVID-19 research on the presumption that it would be, as recent evidence has borne out, an evolving targetand that progress would more likely come from a cluster of approaches than from a single breakthrough.

Since Donald Trump took office, his Administration has worked to systematically disassemble key elements of federal pandemic planning. In 2018, it largely disbanded the National Security Council unit responsible for pandemic preparedness, which was formed during the Obama Administration, after having ignored the councils playbook for fighting pandemics. It removed Rick Bright, from his job as a Health and Human Services official in charge of vaccine development, after he submitted a three-hundred-page complaint about the Administrations coronavirus response. Most recently, the White House directed the National Institutes of Health to cut off federal grant funding to the EcoHealth Alliance, an organization headquartered in New York that studies the global spread of viruses from animals to humans, and which collaborated on research about coronaviruses with researchers based in China.

But some aspects of the countrys pandemic planning have managed to survive, in large part because they were designed as enduring homes of scientific inquiry into the most dangerous biological threats. NEIDL was conceived to be at once independent of politics and ready to respond in a cohesive way to a national emergency. Its approach represents the polar opposite of the warp speed language popularized for the public.

Theres lots of good work going on across the globe, Corley said. Theres also a lot of junk, because people are rushing. The issue is not just sloppiness; laboratories are inherently artificial environments, and even the most careful work can yield apparent breakthroughs that turn out to be artifacts of the experimental process. When a virus infects human cells grown in a lab, it can mutate slightly. It is possible to spend years developing a therapy for an altered form of a pathogen only to find that that therapy brings no benefit to patients. Corley and his team have been sequencing the genes of their virus samples repeatedly as they work, in order to make sure that the pathogen is not morphing into a form that no longer corresponds with what was originally retrieved from the Seattle patienta time-consuming, but necessary, precaution.

As Corley led me on a tour of the facility and introduced me to its researchers, I got a sense of NEIDLs institutional preference for care over speed. Anthony Griffiths, a virologist and an Ebola expert whose focus is on animal modelling, stated the value of deliberate science plainly. I learned lessons from Ebola. I understand speed, he told me. But, if you do science in a rush, you are at risk of going down the garden path. Griffiths hopes to use observations of the progress of the disease in animal hostsgenetically manipulated mice, golden Syrian hamsters, and rhesus monkeysto learn about its mechanisms and to test possible treatments. This could help determine how much virus has to be present to cause infection, and what the routes to inoculation might be, with the aim of uncovering the dynamics of human immunity against the coronavirus. I would love to be first, but were not going to be, he told me. But we want to put ourselves in the best position to do the kind of work that can help understand the performance of the vaccine, and what its limitations may prove to be.

Griffiths works closely with Nahid Bhadelia, an infectious-diseases physician at Boston Medical Center who is an expert in emerging pathogens. In 2014, during the Ebola outbreak in West Africa, she was part of a W.H.O. team that treated patients and training local caregivers. Part of her role is to draw the attention of NEIDL scientists to evolving and unexplained clinical findings of COVID-19, such as those that Fauci highlighted, so that they investigate them in the laboratory. For example, she has observed patients who tested positive for SARS-CoV-2, the virus that causes COVID-19, then repeatedly tested negative, and then tested positive again. Have they become reinfected or has their immunity waned? she said. Or were they just shedding virus from the initial infection? With scientists at NEIDL, she is working to take a chronological sequence of virus samples from such patients. Genetic analysis can show whether a patient was carrying the same pathogen at different times, or whether the virus mutated in a way that outflanked the persons immune response. This work will ultimately make it easier to assess the likely potency of prospective vaccines. Bhadelia has also noted that some patients who were not terribly sick, meaning they werent in the I.C.U, nonetheless appear to have residual problems with cognition. Such persistent effects could potentially be modelled in animal studies at NEIDL.

Rob Davey, an Australian microbiologist with a wry sense of humor and hyperkinetic way of talking, is an expert on discovering novel treatments for pathogens. In 2018, while he was working with the biotech company Regeneron, Davey helped identify a kind of antibody that successfully treated Ebola in animal test subjects by latching onto viral proteins and blocking the microbe from entering cells. These antibodies ultimately became treatments for patients with the infection. Since he began working on COVID-19, he has been looking for agents with the potential to disrupt the progress of the disease. He is currently screening almost seven thousand chemicals that he obtained from the Broad Institute (the joint HarvardM.I.T. enterprise that specializes in assembling large libraries of chemical compounds), along with an additional thirty-two hundred provided by B.U. Some of these compounds are drugs already in use for illnesses including diabetes, hypertension, and migraine. If Daveys screening process indicates that one of them has potential as a COVID-19 treatment, testing on patients could follow quickly, since they already have F.D.A. approval.

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The Long Game of Coronavirus Research - The New Yorker