A Chance Discovery May Lead to a Vaccine for Depression and PTSD

It’s not what she was looking for, really. Neuroscientist Rebecca Brachman was in a cash-strapped lab studying emotional behaviors in mice when a shortcut led her to a startling result. For the over 16 million people in the U.S. each year with severe depression and the 8 million sufferers yearly of post-traumatic stress disorder (PTSD), Brachman’s accidental discovery may result in medicine that can prevent these debilitating responses to trauma or severe stress. It’s at the very least likely to change the way many think of and talk about mental illness.

In 2013, Brachman was working in the lab at Columbia University with her colleague Christine Ann Denny, and they were investigating the human anesthetic — and possible anti-depressant — Calypsol’s effect in mice. Part of their method was using mice who’d been stressed to make them exhibit depression-like behavior the Calypsol could mitigate. “So we would give an injection to mice, and then we’d wait a week, and then we’d run another experiment to save money,” Brachman says in her TED talk. They were re-stressing some mice to run another round of Calypsol tests, but it didn’t work: “They looked like they had never been stressed at all, which is impossible,” she recalls. It turns out the mice had been the ones who’d been administered Calypsol a week earlier — it seems it had somehow inoculated them against the effects of stress.

Brachman and Denny were skeptical, and so they recreated the process, deliberately this time. “And I remember us yelling, which you’re not supposed to do in an animal room where you’re testing, because it had worked,” says Brachman. “It seemed like these mice were protected against stress, or they were inappropriately happy, however you want to call it. And we were really excited.”

They tried it again with mouse exhibiting symptoms of PTSD. It worked. And “we ran it again in a physiological model, where all we did was give stress hormones.” And it worked.

The duo nonetheless found their results hard to believe so they had their grad students try it, as well as some colleagues across the ocean in France. All of the tests verified their impression: The Calypsol has acted as a vaccine, immunizing the mice against stress for weeks. They had stumbled across the first drug that enhanced resilience. And “we only gave a tiny amount of the drug, and it lasted for weeks, and that’s not like anything you see with antidepressants.” Since their research was published in 2014, other labs have verified their conclusions.

In her TED talks, Brachman notes that accidental discoveries like theirs are hardly unprecedented in science, nor does it diminish the discoverer’s achievement. She quotes Louis Pasteur: “Fortune favors the prepared mind.”

Brachman continues conducting research at Columbia, and she and Denny have founded biotic startup Paravax, a company developing what they’re calling “paravaccines,” vaccine-like prophylactic drugs. She’s also involved in a non-profit that’s investigating the repurposing of generic medications for the same purpose.

Brachman hopes, of course, that her discovery leads to human paravaccines to help reduce the incidence of depression and PTSD. She hopes to begin testing on humans next year. In particular, they may be of use to first-responders, emergency workers, and military personnel heading into exceptionally stressful situations. Bachman doesn’t envision paravaccines being used by people genetically predisposed to mental illness.

Calypsol is also known as “ketamine” and is already FDA-approved. It’s used internationally as a legal anesthetic and as an illegal recreational psychedelic, “Special K.”

What also excites Brachman is the notion that the discovery of a medication targeting depression and PTSD will demonstrate to many mental-health skeptics that these are real diseases, with physiological underpinnings. “I think once we have treatments for diseases, or preventions for them, it really changes the conversation,” Brachman tells the Washington Post. “Things are stigmatized in part when there’s nothing you can do about it. They’re also mythologized when there’s nothing you can do about it.”

Only time will tell what happens next after this surprising discovery.” Brachman’s wish is this, though: “It is possible that 20, 50, 100 years from now, we will look back now at depression and PTSD the way we look back at tuberculosis sanatoriums as a thing of the past. This could be the beginning of the end of the mental health epidemic.”