At the start of 2022, as the Omicron variant of the coronavirus blazed across the United States, Seema Lakdawala was in Pittsburgh, finalizing plans to open a brand-new day care. She had found the perfect facility and signed the stack of paperwork; she had assembled a hodgepodge of plushies, puzzles, and toys. It was the perfect setup, one that “I’ve been dreaming about for years,” Lakdawala, a virologist at Emory University, told me. She couldn’t help but swell with pride, later that spring, when she ushered in her establishments’ first attendees: five young ferrets—including one deliberately infected with the flu.
Over the next several months, Lakdawala and her colleagues watched several cohorts of ferrets ping-pong flu viruses back and forth as they romped and wrestled and frolicked inside of a shared playpen. The researchers meticulously logged the ferrets’ movements; they took note of the surfaces and other animals that each one touched. Their early findings, now being prepared for publication in a scientific journal, could help researchers figure out how flu viruses most efficiently spread in group settings—not just among ferrets, but among human kids.
Aerosols, droplets, face-to-face contact, contaminated surfaces—there are plenty of ways for flu viruses to spread. But the nitty-gritty of flu transmission remains “pretty much a black box,” says Aubree Gordon, an epidemiologist at the University of Michigan. Despite decades of research, “we really don’t know the relative importance of each potential route.” Now, though, ferrets in playpens could help researchers to tease out those dynamics—and even, someday, to design flu-blocking measures for bona fide day cares.
Ferrets have long been the “gold standard for influenza infection and transmission,” says Nicole Rockey, an environmental engineer at Duke University who led the experiments with Lakdawala. The animals’ airway architecture is uncannily similar to ours, and unlike most lab mice, ferrets are vulnerable to catching and passing on flu viruses—even developing the same coughy, sniffly symptoms that so many humans do. But most flu-transmission experiments in ferrets remain limited to artificial circumstances: pairs of animals in tiny cages with dividers between them, where scientists ogle them inhaling each other’s air for days or even weeks. That’s not how animals catch one another’s infections in the wild, and it’s certainly not how human outbreaks unfold. “We don’t interact with each other for 48 hours straight through a perforated wall,” Rockey told me.
A giant playpen outfitted with toys, air samplers, and video cameras isn’t exactly a natural habitat for a ferret. But the setup does tap into many of the animals’ impish instincts. Domesticated by humans over thousands of years, ferrets “are a very playful species, and they love to be social,” says Alice Dancer, an animal-welfare researcher at the University of London’s Royal Veterinary College. That makes them great models for not just flu transmission, but flu transmission among kids, who are thought to be major drivers of outbreaks. In their day care, the ferrets squabble over toys, clamber up play structures, and canoodle plush snakes; they chase one another around, and nap in big piles when they get tuckered out; they exchange affectionate nuzzles, bonks, and little play bites. Every interaction represents a potential transmission event; so, too, do the surfaces they touch, and the shared pockets of air from which they all breathe.
Already, the researchers have collected some results that, Lakdawala told me, are “changing the way I think about transmission a little bit.” In one early experiment, involving an infected animal cavorting with four uninfected ones, they were surprised to find that the ferret with the least direct contact with the flu “donor” was the only “recipient” in the room who got sick. It seemed counterintuitive, Lakdawala told me, until video footage revealed that the newly sickened recipient had been copying everything that the donor did—chewing the toys it chewed, rolling the balls it rolled, swiping the surfaces it swiped. It was as if the first ferret was leaving a trail of infectious breadcrumbs for the second one to snarf. If that finding holds up in other experiments, which the researchers are analyzing now, it could suggest that contaminated surfaces, or fomites, are playing a larger-than-expected role in passing the virus around, Rockey told me.
Another of the team’s early findings points to a similar notion. When the researchers cranked up the ventilation in their ferret day cares, hoping to clear virus particles out of the air, they found that the same proportion of uninfected ferrets ended up catching the virus. This was disappointing, but not a total shock given how paws-on ferrets—and kids, for that matter—are with one another and their surroundings. It didn’t matter if the air in the room was being exchanged more than once every three minutes. Whenever the ferrets had their run of the room, the researchers would find virus particles smeared on the toys, the snack station, and the playpen walls.
Ventilation wasn’t totally useless: More air exchanges, the team found, did seem to reduce the concentration of flu genetic material in the air, and the ferrets who got infected under those conditions were slower to start shedding the virus—a hint, Lakdawala thinks, that they might have taken in a lower infectious dose. Among humans, that might translate into less severe cases of disease, Gordon told me, though that would need to be confirmed.
Whatever upshots Rockey and Lakdawala’s ferret findings might have for human day cares won’t necessarily apply to other venues. In offices, hospitals, and even schools for older kids, people are generally a lot less tactile with one another, and a lot better versed on hygiene. Plus, adult bodies just aren’t built like kids’, says Cécile Viboud, an epidemiologist at the Fogarty International Center at the National Institutes of Health. Their airways are bigger, stronger, and more developed—and some experiments suggest that, for at least some respiratory viruses, the older and larger people are, the more infectious aerosols they might expel. For adults, ventilation may matter all the more.
Lakdawala and her colleagues are still mulling some other interventions that might work better for ferrets, and eventually kids: humidifiers, air purifiers, targeted cleaning, maybe even keeping individuals from crowding too closely into a portion of the playpen. (They don’t plan to experiment with handwashing or masking; imagine the difficulty of strapping an N95 to a ferret’s face.) Lakdawala is also mulling whether surfaces made of copper—which her team has shown can render flu viruses inactive within minutes—could play a protective role.
But everything that happens in the ferrets’ playpens will still come with caveats. “It’s still an animal model, at the end of the day,” Viboud told me. For all the similarities between the ferret airway and ours, the way their little noses and snouts are shaped could affect how they cough and sneeze. And the researchers haven’t yet studied spread among ferrets with preexisting immunity to flu, which some day-care attendees will have. Ferrets are also more inclined to bite, wrestle, and defecate wherever they please than the average (potty-trained) kid.
Still, for the most part, Lakdawala delights in how childlike the ferrets can be. They’re affectionate and mischievous; they seem to bubble with energy and glee. After discovering that the air-sampling robot stationed in the center of their day care was mobile, several of the ferrets began to take it for rides. In watching and sharing the footage at conferences, Lakdawala has received one piece of feedback, over and over again: Oh yeah, parents tell her. My kids do that too.
Katherine J. Wu
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