Mice bred at the Jackson Laboratory

Jennifer L. Torrance/Jackson Laboratory

Faced with her lab’s imminent closure, Sunny Shin had already begun to fear she would have to euthanize large numbers of the mice she works on. Then, last Tuesday, the email came from her school’s vice provost of research. “In response to the public health crisis caused by COVID-19,” it read, “mouse/rodent users should cull their colonies as much as possible.”

Shin, a microbial immunologist at the University of Pennsylvania Perelman School of Medicine, had to deliver the bad news to her lab manager: Euthanize 200 mice—more than three-quarters of their research animals—as quickly as possible. Many of the rodents had come from Europe and Asia, and it had taken years to obtain them and breed them for the genotypes the lab needs to study how the immune system responds to bacterial invaders. “It was heartbreaking,” Shin says, “scientifically and emotionally.”

Shin’s lab isn’t alone. Last week, confronting the possibility of extreme animal care shortages and disruptions to research, universities across the country asked labs to think hard about the mice they actually need, to freeze the embryos of valuable or unique strains, and—in many cases—to cull the rest.

As thousands of the rodents began to be euthanized—they are typically killed with carbon dioxide, and their necks are broken just to make sure—the animal rights group People for the Ethical Treatment of Animals (PETA) first called attention to the efforts, blasting them as a “killing spree.” “Why are these animals—when the experiments were approved by the school’s oversight body—now so easily discarded?” asks Kathy Guillermo, a senior vice president at the organization. “Experimenters are again choosing the path of convenience and simply killing animals who should never have been bought, bred, or experimented on in the first place.”

But the heads of major lab animal facilities say the efforts are needed to ensure both the safety of their staff and the welfare of the remaining animals in their care. Given the possibility of veterinarians, technicians, and other workers getting sick or being forced to stay at home, lab animal facilities need to make sure they have the resources to feed, clean, and provide medical care to thousands of animals, says Peter Smith, associate director of Yale University’s Animal Resources Center. “This is a difficult situation for everyone, and I assure you the decision to euthanize animals is not made lightly.”

Eric Hutchinson, director of research animal resources at Johns Hopkins University, Baltimore, agrees. “We are asking our care staff to do the work of two people every day” during this pandemic, says Hutchinson, who has been assisting with much of the culling himself. “It’s grim and sad, but it’s something that needs to done.”

Neither Yale nor Johns Hopkins has mandated that researchers cull their mice. Instead, they have asked scientists to evaluate which animals are “extraneous.” In many cases, this includes mice that would have been euthanized anyway, because, for example, they weren’t born with the genetic profile the lab needed for particular experiments, Hutchinson says. “But instead of making that decision over the course of 2 to 3 weeks, as the researchers would normally do, we’re asking them to make it in 48 hours.”

In other cases, scientists are being asked to identify mice that should be euthanized if the animals get sick or injured (rather than trying to save them), or if there’s no realistic way the lab is going to be able to work on them in the coming weeks or months. “It’s not the five mice you don’t need this week,” Hutchinson says. “It’s the 30 you don’t need this month.”

The result, Hutchinson adds, is that his facility has been performing 2 to 3 weeks’ worth of culling in the course of a single week. Still, he says, neither he nor the university is forcing researchers to sacrifice their mice. “We have not and will not euthanize any animals just to conserve resources,” he says. “We’re just asking investigators to re-evaluate which animals they actually need.”

Not everyone has that flexibility. Isabella Rauch, an immunologist at Oregon Health & Science University, was told last week that she had to get rid of all mice she could otherwise later get from a vendor and any that were not critical for experiments. The lab owns more than 200 mice, which it uses to study how the lining of the intestine reacts to infections. It had to euthanize two-thirds of them. “I was staring at my mice one by one and deciding who lives and who dies,” Rauch says. “It was really rough.”

Hopi Hoekstra, an evolutionary biologist at Harvard University, has already euthanized nearly half of her lab’s approximately 1000 mice. Her team studies wild populations of the animals to understand the impact of genes on social and other behaviors. “Our strains are not found anywhere else in the world,” she says. “If their numbers get too low, they will be lost forever.” She says the culling has taken an emotional toll on the people in her lab. “When you do behavior experiments, you need to watch these animals for hours—you really get to know them,” she says. “We care a lot about these animals. It’s giving me gray hair.”

At the moment, Science has not seen evidence that larger animals such as cats, dogs, or monkeys are being proactively euthanized—and PETA has not made that claim yet. Hutchinson says he expects that to remain the case. Unlike larger animals, he says, mice breed quickly and must be used quickly. And because they comprise about 95% of all research animals, they suck up the most money and time.

Hutchinson and Smith say that if a cat or dog could not be used because of the pandemic, they would adopt it out. “We have two beagles whose study was canceled, and we are lining up adoption for them,” Smith says.

But things could get worse for mice. “If staffing shortages were to reach a point where we could no longer appropriately care for the animals, then we might be faced with some tough decisions to preserve animal welfare,” Smith says. Unlike many other universities, neither Yale nor Johns Hopkins has banned mouse breeding, but that could be the next step if things get worse, Hutchinson says. (On Friday, the U.S. National Institutes of Health [NIH] banned its scientists from ordering new animals, but it hasn’t said whether it has begun to proactively cull mice.) And Smith says Yale may eventually need to begin to mandate the euthanasia of some mice if his facility doesn’t have the staff to care for them.

Meanwhile, Jackson Laboratory, the world’s largest supplier of mouse strains to universities and other institutions, says it has not increased its culling. But it is getting more requests from labs to help them cryopreserve valuable strains—freezing down sperm or embryos that can later be thawed.

That could help restart colonies when labs are up and running again. And Hutchinson says he hopes his efforts at Johns Hopkins to preserve as many mice as possible will help scientists rapidly return to their research. “It puts more strain on our staff to be ready for that, but we’ve had Nobel Prize winners volunteer to come in and clean cages just to keep things running,” he says. “If we have to shelter in place, we’ve got cots and food here just in case.”

Still, scientists are preparing for the worst. Rauch says her university is currently at “Level 3.” If it goes to Level 4, she says she’ll need to narrow her colony down to just the 10% of mice her experiments absolutely require. “I’m very hopeful we won’t get there.”

Shin’s university has told its scientists that the current situation is “likely to last for months,” and that they should be prepared for the impact on their research. “It’s going to take us 6 months to get back up and running when we return—and we have no idea when that will be,” she says. “We have a manuscript out for review, and I just submitted my [NIH] grant renewal. If they ask for more experiments, I’m not sure what we can do. I hope they’ll be understanding.”

Given the disruptions the mouse culling will have on the projects of her lab members, Shin also worries about her two senior postdocs, who were both planning on entering the job market this fall. Will they have the papers they need? Will they be able to get positions?

But for now, she is trying to focus on the big picture. “My whole lab has come together. We realize we have to do these things for the safety of our animal care staff and for the community at large,” she says. “It’s painful, but none of us feel our research is more important than our duty as citizens.”

source: sciencemag.org

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