The Atlantic: "The AI That Agrees With Everything"

Rats can’t vomit. That’s a problem for medicine. - The Atlantic Thirty years ago, antidepressant research seemed on the verge of a major breakthrough. Years of experiments with laboratory rats and mice —animals long considered “classic” models for the condition—had repeatedly shown that a new drug called rolipram could boost a molecule in the rodent brain that people with depression seemed to have lower levels of. Even guinea pigs and chipmunks seemed susceptible to the chemical’s effects. Experts hailed rolipram as a potential game changer—a treatment that might work at doses 10 to 100 times lower than conventional antidepressants, and act faster to boot.

 But not long after rolipram entered clinical trials in humans, researchers received a nasty surprise. The volunteers taking rolipram just kept throwing up . Terrible bouts of nausea were leading some participants to quit taking the meds. No one could take rolipram at doses high enough to be effective without experiencing serious gastrointestinal distress. Years of hard work was literally getting flushed down the tubes. Rolipram wasn’t alone: Over the years, millions of dollars have been lost on treatments that failed after vomiting cropped up as a side effect, says Nissar Darmani, the associate dean for basic sciences and research at Western University of Health Sciences.

 The problem in many of these cases was the rodents, or, maybe more accurately, that researchers had pinned their hopes on them. Mice and rats, the world’s most commonly used laboratory animals —creatures whose many biological similarities to us have enabled massive leaps in the treatment of HIV, cardiovascular disease, cancer, and more—are rather useless in one very specific context: They simply can’t throw up.

 Vomiting, for all its grossness, is an evolutionary perk: It’s one of the two primary ways to purge the gastrointestinal tract of the toxins and poisons that lurk in various foodstuffs, says Lindsey Schier, a behavioral neuroscientist at the University of Southern California. But rodent bodies aren’t built for the act of throwing up. Their diaphragm is a bit wimpy; their stomach is too bulbous, their esophagus too long and spindly. And the animals seem to lack the neural circuits they’d need to trigger the vomiting reflex.

 And yet, rodents make up nearly 40 percent of mammal species and have colonized habitats on every continent on Earth except Antarctica—including homes laced with delicious, bait-laden rodenticides. Part of their secret might be pure prevention . Rodents have exquisite senses of smell and taste, which work as “gatekeepers of the gastrointestinal tract,” says Linda Parker, a behavioral neuroscientist at the University of Guelph. They’re also extremely wary of new foods, and their memory for a sickening substance is strong . “They’ll avoid it for months, years, maybe even their whole life,” Parker told me. “It’s probably the strongest form of animal learning we know.”

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