May 14, 2023
Sometimes mental health research involves getting out of the dark cave of the neuroscience lab and having an adventure. DOOR lab researchers recently went on such an adventure to the mountains of San Diego, California, and became among the first in the United States to visit three rare Siberian foxes with a significant scientific history. Principal Investigator Dani Dumitriu, MD, PhD, views such field trips as part of the lab’s creative approach to generating new knowledge.
This creative approach enables the DOOR lab to help address the lag in mental health research breakthroughs compared to other clinical fields. This lag impedes healthcare practitioners’ ability to address the nation’s burgeoning mental health crisis, despite massive public investment in research. Clinicians have identified various causes of this lag, some related to aspects of laboratory animal models in understanding neuropsychiatric diseases. However, few are asking a more fundamental question: Is the study of inbred animals living in artificial environments an effective method to identify mental health treatments for humans living in non-laboratory habitats?
Dani is asking that very question, and conducting research to provide answers. Her research goal is to understand and harness the brain’s “neurocircuits of resilience” to create novel approaches to mental illness prevention, not just treatment of symptoms. Much of this research involves capturing wild rats to behaviorally characterize, take samples, chip, then release them back into the wild.
In pursuing her passion for results, Dani also studies animal models and the “genetic drift” that happens with lab animals over generations due to human contact. “If you understand the lab animal,” she says, “you understand why the lab animal has not created more actionable treatments.” As she learned about the 170-year history of the lab rat, she remembered a documentary about The Russian Farm-Fox Experiment. Conducted in the 1950s by Dmitry Belyayev with Siberian foxes, it’s the best-known study to date on “domestication syndrome”. First noticed by Charles Darwin, domestication syndrome refers to physical and behavioral traits that are shared among domesticated animals, but not with their wild ancestors. Some of those traits Belyayez produced in the foxes were floppy ears, turned-up tails, piebald coats, di-estrous reproductive cycles, a craving for human attention, and later, shorter and wider faces.
Dani realized Belyayev’s research might inform her own study of lab rats, especially behavioral genetics and “selection for tameness”. It could help us understand whether stress responses we observe in the lab are the result of evolutionary pressures or behavioral selection in the lab. When Dani discovered that a couple in San Diego, California, had purchased three of the Siberian foxes from Russia and were planning to start a sanctuary. The timing was perfect, since she was already planning to take seven researchers from her lab to a conference in the area, so she called the couple and asked for a tour.
“I was dying to see the Siberian foxes but the sanctuary wasn’t open, ”she recalls. “I emailed them and said, ‘I have a lab at Columbia. I study wild rodents. This is such a cool thing and I really want to come.’ But they said we’re not open, we don’t even have a toilet, not even running water! I said, ‘It's fine. I don't care.’
The sanctuary owners agreed, and Dani and her colleagues found themselves riding in a rented minivan up a winding mountain road to Santa Ysabel in November 2018. She hadn’t told them where they were going, just that it had to do with their wild rat experiments. “Everybody was guessing and there were wild guesses,” she chuckled, “But no one guessed that they were gonna see Siberian foxes.”
The team was incredibly surprised when they arrived. Following a lecture, they got to pet and play with the foxes, and were very attentive. “I think this shows we're creative and fun and we try to learn in ways that aren’t just in the lab,” says Dani. “We do sit in dark rooms at microscopes to try to understand the difference between wild rats and laboratory rats, but we're also trying to learn from other opportunities as they arise. And this was a once in a lifetime opportunity.”
Dani reflects that these kinds of experiences, along with academic freedom, are what make the grueling road to becoming independent faculty worth it. She’s also taken advantage of her freedom and status to pause and contemplate big questions. “I sat and thought for a very long time … about what big problem in the world I’m going to fix, ”she recalls. “You get the academic freedom to be very creative about how you approach the new knowledge you're going to generate. This trip was one of my first early experiences with that creative process as an independent academic.”