Covid-19 has shuttered labs. It could put a generation of researchers at risk – STAT

Scientists are skilled at tackling unexpected problems that threaten the integrity of their experiments it comes with the territory. But the coronavirus pandemic poses a new and entirely unprecedented challenge.

The global health emergency has shut down scientific research labs across the country in a crisis that has left some scientists scrambling to save their work and has left others grieving the loss of experiments they had dedicated months or even years to carrying out. Many are grappling with an overwhelming sense of uncertainty about how theyll continue their work.

The situation has hit early-career researchers particularly hard. Their funding and their futures depend on quickly gathering data to publish in prestigious journals. Without additional financial support and an extension of tenure clocks, some scientists who have just started their own labs fear the delays to their studies may be too disruptive to overcome.

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Early-career scientists will be very vulnerable, said Cullen Taniguchi, assistant professor at University of Texas MD Anderson Cancer Center. Taniguchi said it will be crucial to properly support researchers when labs reopen or, he warned, we may lose a whole generation of researchers because of this.

Despite these struggles, many researchers say that shutting down the labs was necessary to stem the spread of the virus. And some labs are still up and running, though not all are doing so at full capacity. But for scientists whose work has been deferred, the closures have fueled a devastating ripple effect of consequences, both big and small.

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Even when laboratories are reopened, it may take months to a year for research to resume as normal.

I have [new hires] in the lab that havent even met each other physically, said Alice Soragni, a cancer researcher and assistant professor who runs a lab at the University of California, Los Angeles. There is a lot of training that needs to have happened that hasnt happened, she added.

STAT spoke to scientists across the country to better understand the wide-ranging impacts of lab shutdowns.

Scientists have transitioned from long hours in the laboratory to working from home but the abrupt halt to their research projects has left a lingering sense of disorientation for researchers like Kathleen Beeson, a sixth-year graduate student at Oregon Health and Science University.

Like many of her colleagues, Beeson was caught off guard by her labs closure.

We were given a weeks notice,she said. Immediately, I and others were in a race to finish experiments, collect any data that we could, and get the lab prepared for a minimum of six weeks of shutdown.

Beeson had been completing a final experiment for a publication she needs to earn her Ph.D. and move onto a postdoc research position at Harvard Medical School.

The shutdown has upended Beesons research, which involves measuring electrical activity in the brains of genetically engineered mice. Her work aims to describe how proteins at the junction of nerve cells help transmit chemical signals an important step in understanding neurological dysfunctions such as epilepsy.

While other scientists were able to freeze cells or preserve tissue samples in formaldehyde, Beesons research relied on analyzing freshly dissected brain tissue. Because she could no longer come into the lab, she had to sacrifice most of her mouse colony, which she had painstakingly raised from one male and one female to approximately 200 animals.

In the end, I found myself euthanizing mice by the masses in the university basement, she said. It was the punctuation on a sad and disorienting week.

Beeson said it will likely take her months to raise enough animals for experiments again. In the meantime, she has been working on her Ph.D. dissertation and a second publication from home although not at the pace that she had hoped for.

I applaud anyone making any progress, on anything, during this time, she said. Sometimes my progress is processing my grief.

Disruptions to research and long startup times pose an especially daunting challenge to early-career scientists who have just a few years to establish themselves as experts in their fields and obtain critical funding for their laboratories.

With experiments on hold, some early-career scientists cant collect the kind of preliminary data that is crucial for them to compete with more established researchers who have a decade or more of experimental findings to build on.

[All researchers] are impacted but I think there are exquisite challenges for early-career investigators like myself, said UCLAs Soragni.

To protect early-career scientists, the NIH has extended the time frame for which researchers can be considered early stage investigators a status that helps government institutes and centers prioritize funding for scientists running new laboratories. The agency has also relaxed some of the eligibility requirements for maintaining grants and added additional flexibility for spending funds.

Despite these welcome efforts, early-career researchers especially those lacking data needed to apply for new grants remain in a precarious position. Soragni and others said they hoped the NIH would take the impact of Covid-19 into account and temporarily adjust its criteria for reviewing applications. However, the agency has recommended that scientists without enough preliminary data submit their applications at a later date.

For Soragni, the most difficult challenge has been the uncertainty.

You are kind of left not knowing what you should do. Should you be ramping up completely? But what if you are switched down again?

Alice Soragni, UCLA cancer researcher

We really dont know if we are going to have a second wave of infections and what will be the consequences, she said. You are kind of left not knowing what you should do. Should you be ramping up completely? But what if you are switched down again? Should you be hiring? Will the economy bounce back? What is going to happen to your grants?

We are just at a more vulnerable stage of our career, Soragni said. I believe we may lose some laboratories to this, so that will be very painful to witness.

The shutdowns have taken a toll not only research, but also on the close professional relationships at the heart of scientific collaboration.

For Stephanie Campos, Covid-19 meant that she would not complete her research or be able to say goodbye to her mentor, Walter Wilczynski, in person. Campos had come to Georgia State University for a postdoctoral fellowship with Wilczynski, a pioneer in the field of behavioral neuroscience and the first director of the universitys Neuroscience Institute. But after 37 years of research, the lab was scheduled to close this summer after Wilczynskis cancer, once in remission, returned.

Campos and her colleagues were wrapping up their research a study of the brain activity in lizards aimed at unraveling the neural underpinnings of social behaviors when the pandemic hit. The lab shuttered earlier than expected.

With the laboratory closed, Campos has been limited to writing manuscripts from home and analyzing old videos of lizard behavior. She cant see Wilczynski who is immunocompromised again in person before she moves to a new role as a visiting assistant professor at Swarthmore College.

[This experience] has really affected me emotionally in the way that I knew I was going to be his last student, Campos said. And so I had really wanted to get as much as I could.

With Georgia easing restrictions on social distancing, there is a possibility that Campos could return to the lab late in the summer, but she is still unsure if returning to work would be socially responsible. Instead, she is planning on mailing the bulk of her delayed research project which involves 68 lizard brains preserved in vials of paraformaldehyde to Pennsylvania, where she will begin work in August.

Campos credits Wilczynski, who was at times too fatigued to read papers, for guiding her through the gauntlet of an academic job search and giving her the confidence to continue in academia.

His kindness during this time is what Ill remember the most, Campos said. For me it is all about the personal connection, how well your mentors make you feel. Those are the things that I will take away.

Waiting for their labs to reopen, principal investigators are steeling themselves for the months of effort that will be needed to reestablish the rhythms of a productive laboratory.

Theres a mountain of work to muddle through before experiments can get off the ground again.

We will have to first retest [our equipment] to make sure it is working, regrow our [bacterial] cultures, which takes a while, before we can even consider doing an experiment, said Eric Rubin, an immunology and infectious diseases researcher and professor at the Harvard T.H. Chan School of Public Health. Rubin also the editor-in-chief the New England Journal of Medicine.

Regrowing bacteria in Rubins laboratory is not a job for the impatient. The focus of his studies, Mycobacterium tuberculosis, causes tuberculosis and kills more people worldwide than any other infectious pathogen. M. tuberculosis also grows approximately 50 times more slowly than other microorganisms. Experiments that would take a day with other commonly studied bacteria typically take weeks in the Rubin lab.

When laboratories closed, Rubins team was in the midst of testing a batch of promising drug compounds for the ability to kill the bacteria. To resume the study, researchers will have to thaw out stocks of frozen bacteria and coax them to replicate in liquid broth.

We normally always have things growing so that we can grab them and do our next experiment, said Rubin. [But now] it will likely take four months before we will have enough cells to do experiments at full tilt again.

Restarting research may take even longer up to a year for those working with laboratory animals, such as Subhash Kulkarni, a scientist and assistant professor at Johns Hopkins University School of Medicine.

In 2017, Kulkarni showed that, contrary to established dogma, nerve cells lining the intestines continue to grow and divide in adult animals. To understand how this discovery could lead to new treatments for digestive disorders, Kulkarni had begun analyzing how neurons behaved over the lifespan of a mouse. This project required raising genetically engineered mice at staggered times to have enough of each age group at the start of the study.

With his lab closed, the entire effort will have to be repeated once Kulkarni is allowed to work again. That timeline is daunting.

Think of this as the time when the planets are in perfect alignment, Kulkarni said. Once that time is lost, making the next time requires [new] breedings, which can take anywhere from six to 12 months.

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Covid-19 has shuttered labs. It could put a generation of researchers at risk - STAT