Closing, reopening labs was a complex experiment

Student working in a lab
Charlotte Wirth works on a human microglia cell line. Alone in her lab that day, Wirth took this photo using a timer.

September 1, 2020—A lab is a little like a giant cruise ship, according to Sarah Fortune, John LaPorte Given Professor of Immunology and Infectious Diseases and chair of the Department of Immunology and Infectious Diseases (IID) at Harvard T.H. Chan School of Public Health. Its multiple moving parts can’t just be shut off with the flick of a switch—tuberculosis specimens must be safely stored, breeding mosquito colonies fed, sub-zero freezers kept running.

When the spreading COVID-19 pandemic forced labs around the University to close down in mid-March with just two weeks’ notice, Fortune and her colleagues faced tough choices. The work of a few researchers involved in projects related to the virus—or with other projects for which a shutdown would cause an “insurmountable loss”—were allowed to continue with minimal personnel. All other lab members had to walk away from their work, losing investments in time, funding, and materials.

“It was a much more complicated effort than I would have ever anticipated,” said Fortune, who sat on research planning committees at the School, Longwood Medical Area, and University. Determining what met the loss threshold was a gray area, she said. “There was some adjudication and a lot of personal sacrifice.”

Labs under lockdown

For the next three months until labs reopened, researchers did what they could at home, analyzing data, writing papers, and participating in Zoom journal clubs and lab meetings.

IID joined with the Department of Biostatistics to offer computational training for bench scientists. Fortune noted that this has already resulted in several members of her lab finding new avenues for research from their datasets.

Charlotte Wirth, a PhD candidate in biological sciences, spent her time working remotely cleaning up data and writing research protocols. A researcher in the lab of Quan Lu, professor of environmental genetics and physiology, she’s investigating whether microglia (a type of immune cell in the brain) secrete extracellular vesicles known as ARMMs—which Wirth describes as tiny packages sent between cells. She wants to understand whether this might be a pathway for the spread of toxic neurodegenerative proteins in the brain.

In March, she was working on a microglia cell line and beginning an exciting new collaboration with a lab at the Icahn School of Medicine at Mount Sinai. There, researchers had developed a cerebral organoid model—stem cells grown into small balls of human brain tissue—containing microglia. Wirth was hoping to obtain some samples from the model to see if they contained ARMMs, but the shutdown of both labs put the work on hold. Her cell lines were frozen to preserve them.

Noman Siddiqi, senior lab director in IID, did a weekly walkthrough of the Department’s labs during the shutdown, ensuring that electrical power was on and expensive equipment still functional. It was a strange experience, he said. “You don’t notice how much background noise there usually is. Then suddenly it’s so quiet.”

Reopening with restrictions

Siddiqi was part of the School’s research planning committee, which, while it awaited word from city and state authorities, developed plans to safely reopen the labs. The committee also helped communicate new procedures to returning researchers and staff, including the University’s new health screening app Crimson Clear—a must for accessing research buildings.

The Operations team was critical to reopening plans as well, adjusting ventilation systems, installing signage with new distancing guidelines, and instituting enhanced cleaning schedules.

With community spread of COVID-19 improving in Massachusetts, labs were able to open on June 8. Initially, they were only permitted to bring back 25% of their workforce at a time. Researchers were assigned to a cohort with either a morning or evening shift, and required to clock in and out on schedule. This allowed for enhanced cleaning between shifts and kept cohorts separate, minimizing the number of people who would need to be quarantined if someone got sick. By late July, labs were able to increase their density to 50% and to loosen their rules somewhat, for example, by letting researchers stay past the end of their shift to finish work.

Fortune noted that many researchers are still facing challenges as they restart their research—and junior faculty tend to be struggling more than senior faculty. “It’s a much bigger hit to stop your fledgling research program for three months and then crank that wheel back up.”

Tony Hui, assistant professor of molecular metabolism, joined Harvard Chan School just two months before the shutdown. His research focuses on aspects of energy metabolism, including cachexia—weight loss and tissue wasting associated with cancer and other diseases. He uses a procedure called flux quantification that measures metabolism in mouse models. So far, all he’s been able to do is run some experiments on blood and tissue samples he’s received from other labs. He hasn’t been able to set up his own mouse models or fully staff his lab, and even small logistical challenges have turned into major headaches.

“In normal times, when I had a problem setting something up, I could solve it just by going out into the hallway and talking to someone,” he said. Now, with researchers heading to their labs without lingering to chat, it’s much harder to find a helpful colleague.

For Wirth, “Not being able to do any new research for three months was a huge hindrance, especially since I was starting my third year of graduate school. That’s when you get out of the classroom and into the lab full time.”

Now back to work, she’s learning what she can from her cell lines. But she’s unsure when, or if, she’ll have access to the organoid model. There has been one small, positive takeaway from the past few months, she said—stricter shifts at the lab have taught her how to be more efficient with her time.

Fortune said she’s learned that a lot of work travel is not necessary, especially as budgets tighten. While some personal interaction is lost when meetings and conferences go online, she said, the upside is that more people are able to participate.

The bigger loss is the daily personal interaction that happens in the lab, Fortune said. She has not been back yet—she and a number of other faculty members have given over their offices so that researchers have more space to eat their lunch and relax—but she’s heard that things are not the same. Social distancing diminishes a lab’s family atmosphere and the moments of inspiration that can spring from spontaneous conversations, she said. “It’s working, but I can’t pretend that something precious hasn’t been lost.”

Amy Roeder