On a normal day, Maddie LaRue would wake up, head to her lab and get to work.
As a PhD candidate at New York University studying pancreatic cancer, and just months away from defending her thesis, she’s spent years getting to this point – years of cultivating a mouse colony with a particular genetic composition, harvesting cells from those mice, and then growing the cells in petri dishes to study their metabolism. Her goal: to understand how pancreatic cancer cells grow. And the pursuit of that goal requires a daily presence, not only to run experiments and analyze results but to simply ensure that the mice and cells are cared for and maintained.
But with Covid-19, the disease caused by the novel coronavirus, proliferating throughout the US, these are not normal days. While there is a tremendous effort underway to understand and develop a vaccine for the coronavirus, scientists such as LaRue – who do vital research to further our understanding of biology, pathology, evolution, insect flight and countless other fields – are forced to stay home. And only time will tell what affect this will have on scientific progress in the US.
In parts of the country, like New York, state-wide mandates aimed at limiting the risk of contagion now prevent all non-essential workers from entering their labs. In other areas, many institutions are setting their own regulations to this effect; the National Institutes of Health has moved all “non-mission-critical laboratory operations” to maintenance mode. With the number of Covid-19 cases worldwide topping 788,500, and more than 160,700 in the US, these measures are necessary. Yet they also leave labs with few essential personnel to preserve mice of critical genetic lineages (or “strains”) and crucial research resources – and no one to progress most of the ongoing experiments.
Researchers such as LaRue, who has been out of the lab for more than two weeks, are growing worried about the consequences of halting their studies, particularly those utilizing animals that can be costly and time-intensive to genetically engineer or breed. Even if the necessary animal strains survive the shutdown, experiments that are time- and condition-sensitive could still be greatly set back or ruined altogether.
A mouse study, for instance, may require a large sample size of animals of a certain age from a specific mouse strain. Researchers might have had the foresight to freeze embryos or sperm from these mice prior to their lab’s shutdown to make sure that the strain survives, but it can take months, if not years, to get a large enough sample size of mice at a specific age for a robust preclinical trial. And if those mouse strains were to be lost entirely, it would mean a lot of time – not to mention thousands of dollars’ worth of mouse maintenance – down the drain.
Setbacks in animal research could also have tremendous downstream effects on our ability to understand and treat human pathologies. Discoveries made in animal models can often serve as fuel for human drug development. This is the case for LaRue’s lab, which focuses on drug target discovery. Her lab’s goal is to publish academic papers that show potential drug targets for pancreatic cancer therapies.
“[Drug companies] really utilize the scientific literature, and most of the literature is coming out of big academic labs,” said LaRue. “If academic labs are shut down for months and research continuities are disrupted, it’s going to take several more months to gain momentum again and people won’t be producing results for some time … That could really put a lag on the drug discovery pipeline that we have going with industry.”
And while researchers are sitting at home, writing up manuscripts or planning out future experiments, they must do so without the spontaneous, collaborative brainstorming that inspires creativity and facilitates troubleshooting. “Our day-to-day is based on interactions with others … bouncing ideas off of other people in a way that’s difficult to do when we’re all working remotely,” said LaRue.
Once labs have re-opened, experiments resume and social distancing is a distant memory – one final uncertainty could still present an additional hurdle for the scientific community: research funding. As the economic reality of this pandemic sets in and funds are reallocated to relief programs to get the country up and running again, will there be any left for scientific grants?
“That’s my greatest fear. What’s going to happen at large to the finances in our society?” said Brian Schutte, an associate professor of microbiology and molecular genetics at Michigan State University, whose research centers on identifying genetic factors associated with cleft lip and palate. His lab uses mice, too, in this case to study the mechanism that causes the birth defect. But with a capable team of essential personnel staffed during his lab’s shutdown to maintain the mouse colonies, Schutte is confident that his research can rebound if the lab re-opens within a couple of months.
Funding, however, or a lack thereof, may indeed pose a greater threat to Schutte’s lab and countless others across the country that are supported by government-sponsored grants. Though industry, state and local budgets, as well as universities themselves, play a role in funding research, institutions still rely on federal grants to support their vast research portfolios. If future funding dwindles in the wake of the pandemic, projects already hindered by costly delays will face an uphill battle to be completed while new projects struggle to get off the ground.
Addressing the immediate concerns from the scientific community, the Office of Management and Budget issued a directive this month revising grant requirements and allowing researchers some flexibility while their labs remain shuttered. But as the memorandum notes, “Many of the operational impacts and costs are unknowable at this point, as they will depend on the spread of the coronavirus and response dictated by public health needs.”
A pandemic is, in many ways, like a natural disaster: Once it strikes, we can try to take precautions and preserve what we can, but we won’t know the extent of the casualties until the dust has settled. Not until we are able to take stock of the post-Covid-19 world will we be able to assess the scope of the damage. Certainly, we will mourn the loss of life and bemoan the economic fallout. And we may also lament the stymieing of scientific progress.