UP CLOSE | Socially distant science: How the School of Medicine adapted to research during a pandemic

UP CLOSE | Socially distant science: How the School of Medicine adapted to research during a pandemic

Researchers and administrators have had to prioritize remote research, limit in-person activity and shift their focus to COVID-19-related topics over the course of the last year.

Published on April 9, 2021

On March 18, 2020, as the pandemic rapidly worsened, University Provost Scott Strobel announced that all non-essential medical research would be suspended and should be conducted remotely. Principal investigators, Yale School of Medicine administrators and students had to adapt to the unprecedented challenge of conducting research from home, or being present in the lab studying an unknown virus as it spread across the planet and killed millions.

“It was a really difficult work environment,” Sterling Professor of Molecular, Cellular, and Developmental Biology Anna Marie Pyle told the News. “[But] we didn’t consider ourselves unlucky, we felt really fortunate to have the privilege of being in a position to make a difference.”

Over the course of the last year, investigators have had to limit the number of people present in their labs at any given time, move most of their activities online and, for some, shift their research projects to focus on COVID-19.

The News spoke to administrators, faculty and students at the School of Medicine about changes in research during the pandemic and how they affected their research experiences — as trainees, leaders and scientists during a time when scientific knowledge is especially prominent. Many researchers described a feeling of pride in being able to contribute to the scientific knowledge which was essential to save lives.

We all wanted to help understand how people’s immune system is responding to this virus infection and what goes wrong in those who develop severe and life threatening COVID,” Professor of Immunology Akiko Iwasaki wrote in an email to the News. 

It was a really difficult work environment. [But] we didn’t consider ourselves unlucky, we felt really fortunate to have the privilege of being in a position to make a difference.

—Anna Marie Pyle, Sterling Professor of Molecular, Cellular, and Developmental Biology

Prioritizing remote research

As all non-essential research was moved online, scientists had to adapt their current projects to an online format, an undertaking that proved far easier for some than for others.

According to University Spokesperson Karen Peart, faculty had to submit safety plans developed to follow guidance from the University’s Environmental Health and Safety and COVID-19 Public Health committees. These plans were then approved by their departments in addition to the Dean’s and Provost’s offices.

Professor of Psychology Nicholas Turk-Browne explained that his work on patients already at YNHH — those undergoing surgery for epilepsy, for example — was able to continue since he was able to focus on the parts of his research that did not require bringing subjects into Yale’s campus.

However, since much of his pre-pandemic lab work did involve healthy human subjects, he suspended those studies for over four months, focusing mostly on data analysis and writing papers in the meantime.

[Research on healthy subjects] would have required bringing people to the lab who had no other reason to be on campus during the early part of the pandemic, and then interacting with them in small rooms or at close range,” Turk-Browne wrote in an email to the News.

The focus on remote work was characteristic of most labs. All four of the PIs interviewed by the News said that a main change they implemented was reducing the number of people in the lab at any given moment. Many researchers set schedules in order to rotate between lab members working in person.

For undergraduate students, these changes meant that they were, for the most part, not allowed into the lab they were working in, since many of them performed tasks — such as data analysis — which could be done remotely. With the limit on the number of people allowed in the lab, PIs often prioritized those doing graduate work or who had essential roles requiring their presence in person.

This was disappointing and frustrating for people like Tai Michaels ’23, a research assistant in Iwasaki’s Lab, who had just started working at the lab.

“I joined the lab maybe two or three weeks before spring break,” Michaels said. “So I had just gotten started before everything went remote.”

Since the Iwasaki Lab was considered essential due to its focus on COVID-19 research, one of Michaels’ tasks is remotely analyzing the data that is collected on site by members of the lab.

According to Michaels, before COVID-19 restrictions were relaxed, he had never actually met most of the lab members he was working with. Now, he is able to go to the lab for short periods of time, but is still working mostly on his remote research.

“It was kind of a disconnected experience,” Michaels said. “I never saw anyone in the lab, but I was glad to be able to participate.”

According to Michaels, one of the benefits of working as a remote research assistant was getting involved in different areas of research which were not originally his focus. Michaels explained that during the summer, his work for the Iwasaki Lab focused on data analysis and bioinformatics, which he had never tried before.

Michaels believes that despite the unexpected turn of events in his lab experience, he was able to learn a new skill and contribute to the Iwasaki Lab at an important time — as Iwasaki herself has gained prominence for her COVID-19 research.

However, some labs were able to perform a larger proportion of in-person research. The Pyle Lab, which performs essential SARS-CoV-2 research, was able to maintain in-person activities throughout the pandemic.

I did miss out on physically being in the lab. However, I gained so much through deeply reviewing the literature and building my computational research skills.”

—Kerrie Greene MED '27, Chair of the Department of Music

While adhering to strict safety precautions — such as a requirement for masks, surface decontamination and a rotating schedule of in-person lab members — PIs and students were present in the lab while most of the world remained under lockdown at the onset of the pandemic.

“We were able to have some control over the situation in a way, and most people didn’t,” Pyle said.

Similar to the Turk-Browne and Iwasaki labs, some projects not involving COVID-19 research in the Pyle lab had to be halted or moved online. According to Pyle, lab members working remotely prioritized bioinformatics projects, as well as writing papers and grants, since most of the lab projects required the use of equipment and in-person analyses.

Kerrie Greene MED ’27 explained that she elected to do her summer rotation — a requirement for all medical students — in the Iwasaki Lab remotely. According to her, the beginning of her research time coincided with the start of the pandemic, so her research experience at Yale has always been remote.

“I did miss out on physically being in the lab,” Greene wrote in an email to the News. “However, I gained so much through deeply reviewing the literature and building my computational research skills.”

Funding research

As researchers either pivoted to focus on COVID-19 or shifted their work online, they found themselves worried about funding and grants. The long wait periods for grant approval — between eight to 20 months — were the main source of preoccupation, due to the urgent need for knowledge about the virus, according to three principal investigators and Liliana Lucca, a post-doctoral student in the Department of Neurology.

The National Institutes of Health, the main source of funding for most researchers in the United States, provided expedited pathways for grant approval, as well as flexibility in using already-existing grants for COVID-19 research. When receiving NIH grants, researchers are allowed to redirect those funds into other projects with similar goals, which fit within the broad research lines described in the grant application.

According to Peart, while the turnaround time for grant application approval and manuscript publication has decreased amid the pandemic, the process has largely remained the same.

She also stated that the School of Medicine and the University provides its own funding for researchers. This included both “gap funding” for faculty at the beginning of their careers when the pandemic started — who usually devote more time to research as opposed to teaching or seeing patients — and funding specifically directed for researchers studying the novel coronavirus.

“Additional funding for COVID-19 related research was made available through a university-wide effort led by [School of Medicine Dean Nancy Brown] at the school of medicine,” Peart wrote in an email to the News.

Brown added that the School of Medicine has provided seed money for investigators within the first three years of joining the faculty, regardless of their field of study. Peart said this was a “unique investment related to the impact of COVID” but emphasized that there are “many mechanisms for supporting early-career investigators.”

Still, Peart stated that Yale-funded research grants did not prioritize COVID-focused research over other research focuses, though outside funding agencies might prioritize certain proposals during the pandemic.

She wrote that there was a “temporary dip” in the number of grant applications in the first quarter of 2020, but that overall in 2020 the University saw an increase of 26 percent in the number of grants from the number in 2019. From 2017 to 2019, the number of applications increased by six percent each year.

According to Pyle, many researchers had to use their discretionary accounts — funds raised by investigators that are not assigned to a specific project, and are therefore available for unrestricted use — and outside funding in order to support their projects.

“It’s been a bit of a sacrifice because we’ve had to spend precious funds on that work and have not been compensated for it,” Pyle said. “Despite what’s being said in the media, there’s very little funding for research because it’s a brand new virus.”

Even though there are many reports of large funding opportunities for coronavirus research, especially the bill proposed by the United States government, scientists around the world still struggle to find funding and use it to cover the expenses of essential COVID-19 research.

Assistant Professor of Laboratory Medicine and Immunobiology Craig Wilen explained that since the demand for COVID-19 research was high and there was a great sense of urgency amongst scientists, some researchers started projects before being sure of funding availability. 

He said that the low chance of being funded also encouraged researchers to look for sources of funding other than grants — from the School of Medicine or outside donors.

“I think there’s so much information we needed to look into, that we were hoping that the money would come later,” Wilen said. “[My lab was] fortunate enough to get foundation support and support from generous donors, through Yale, private foundations and targeted donors, and that really enabled us to make progress without having to worry about resources.”

The scientific accomplishment, both the speed and volume, over this pandemic has been truly remarkable. My hope is that more people realize the importance of basic research and the need to invest in future research, in order to be better prepared for future pandemics.

—Akiko Iwasaki, Professor of Immunology

An expedited publishing process

Two researchers also demonstrated concern for the expedited peer review processes of reputable journals, which had to be sped up and restructured due to the high volume and fast-paced production of coronavirus research.

According to Lucca, there was a “long line” of papers waiting to be published, and a “crowding” of journals with coronavirus research. This caused the researchers who were working on other topics to struggle to publish their findings, according to Lucca.

“This comes from a place of good intentions,” Lucca said. “But there have been a lot of COVID studies that have been retracted later on or whose analyses have been critiqued.”

Lucca also said that sometimes, peer reviewers for papers were only given a few days to review papers. as opposed to the several weeks they typically have.

According to Retraction Watch, over 100 papers related to coronavirus research have been retracted, worrying scientists around the world, as some retracted papers made their way into mainstream media and were widely propagated. The Scientist even generated a “Top Retractions of 2020” list, in an effort to emphasize the severity of the issue.

“That side of it has gone badly, in my opinion,” Pyle said. “There’s been a lot of fast publication of report and research, but then there’s also been a lot of bad papers slipped through the cracks.”

Despite these challenges, Peart satiated that there has been an increase in publications by the University’s faculty members of 26 percent. By comparison, the net increase in the two previous years was only 6 percent per year.

Even though the fast-tracking of paper revisions poses issues to the quality of papers published, Iwasaki believes speed in the communication of new scientific knowledge is essential.

“We are able to communicate what we are learning in real time through Twitter and preprint servers, as well as more main stream media,” Iwasaki wrote to the News. 

According to Peart, many faculty members have used preprint servers like bioRxiv and medRxiv to publish their findings more quickly.

Wilen also mentioned that Yale’s hiring freeze implemented on April 7 represented a challenge to PIs who were unable to hire new students and lab members. This restriction, in conjunction with the personnel safety restrictions in place within labs, meant that in-person lab members were under increased stress.

Pivoting research focus

Many basic science laboratories — which do not perform clinical research — were working on viral genome and immunobiology research prior to the pandemic. Once COVID-19 hit, they pivoted their research projects to focus on coronavirus research. Researchers told the News they felt a responsibility to contribute to the knowledge surrounding the novel virus.

The Pyle Lab’s previous research focused on viral RNA and viral genomes, which permitted them to transition their established projects into studying the coronavirus genome and structure.

“Given that it was simple for us to make a few changes in our workflow and sort of address really fundamental problems to understand coronavirus biology,” Pyle explained. “We just decided that it’s the responsible thing to do.”

Researchers such as Wilen also started unique projects designed to address specific issues brought on by the pandemic. For example, the Yale IMPACT team, led by Iwasaki and Albert Ko — of which Wilen was also a member — created a biorepository for COVID-19 samples to be available for researchers. The project spanned a few months and collected samples in partnership with New Haven citizens, health care workers and patients.

According to Iwasaki, medical students in her lab also created a group called Spike Support, which focused on giving Zoom seminars to educate citizens across the United States about the vaccines.

“Transitioning to work on COVID has been truly transformative for me and my lab,” Iwasaki wrote in an email to the News. “The incredible hard work of people in my lab has produced so much important knowledge in such a short time.”

According to Peart, some faculty members expanded the scope of their research in order to accommodate COVID-19 related projects when the pandemic began. This research was supported by the additional funds provided by Brown or by previously-approved grants.

Long-term impacts

I think that going forward there is going to be public support for directing more funds to basic biology so that we understand new types of viruses. We should know more about all these different classes of viruses, so that when one of them becomes really pathogenic like this we have some idea about what to do.

—Anna Marie Pyle, Sterling Professor of Molecular, Cellular, and Developmental Biology

Iwasaki believes that the level of scientific knowledge produced during the pandemic should bring more attention to the importance of basic, non-clinical scientific research.

According to her, the “decades” of basic research dedicated to immunology, virology and vaccines enabled the development of COVID-19 vaccines in such a short timeline and with such high effectiveness.

“The scientific accomplishment, both the speed and volume, over this pandemic has been truly remarkable,” Iwasaki wrote. “My hope is that more people realize the importance of basic research and the need to invest in future research, in order to be better prepared for future pandemics.

Iwasaki also emphasized the transition to online tools, such as Zoom, for meetings which have enabled communication between scientists all over the world and the sharing of their expertise. She believes this practice could be one of the legacies of the pandemic which will improve research in the future.

According to Pyle, one of the positive effects of the pandemic for biomedical research was the media attention and global interest in viral research, which according to her was previously focused on the human immunodeficiency virus.

“I think that going forward there is going to be public support for directing more funds to basic biology so that we understand new types of viruses,” Pyle said. “We should know more about all these different classes of viruses, so that when one of them becomes really pathogenic like this we have some idea about what to do.”

Brown agreed, saying that the pandemic has “brought home” the importance of scientific discovery in ways that will continue even when it ends. The pandemic has stimulated collaboration between labs across the world and highlighted the legacy of innovative research in biomedical science.

“We have RNA vaccines today because of research done years ago,” Brown wrote in an email to the News.

 

Beatriz Horta | beatriz.horta@yale.edu

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