Scientists Tried to Break Cuddling. Instead, They Broke 30 Years of Research.
But as my colleague Ed Yong and others have repeatedly written, most of what’s said about the hormone is, at best, hyperbole. Sniffing the chemical doesn’t reliably make people more collaborative or trusting; trials testing it as a treatment for children with autism spectrum disorder have delivered lackluster results. And although decades of great research have shown that the versatile molecule can at times spark warm fuzzies in all sorts of species—cooperation in meerkats, monogamy in prairie voles, parental care in marmosets and sheep—under other circumstances, oxytocin can turn creatures from rodents to humans aggressive, fearful, even prejudiced.
Now researchers are finding that oxytocin may be not only insufficient for forging strong bonds, but also unnecessary. A new genetic study hints that prairie voles—fluffy, fist-size rodents that have long been poster children for oxytocin’s snuggly effects—can permanently partner up without it. The revelation could shake the foundations of an entire neuroscience subfield, and prompt scientists to reconsider some of the oldest evidence that once seemed to show that oxytocin was the be-all and end-all for animal affection. Cuddles, it turns out, can probably happen without the classic cuddle hormone—even in the most classically cuddly creatures of all.
[Read: The weak science behind the wrongly named moral molecule]
Oxytocin isn’t necessarily obsolete. “This shouldn’t be taken as, ‘Oh, oxytocin doesn’t do anything,’” says Lindsay Sailer, a neuroscientist at Cornell University. But researchers have good reason to be a bit gobsmacked. For all the messy, inconsistent, even shady data that have been gathered from human studies of the hormone, the evidence from prairie voles has always been considered rock-solid. The little rodents, native to the midwestern United States, are famous for being one of the few mammal species that monogamously mate for life and co-parent their young. Over many decades and across geographies, researchers have documented how the rodents nuzzle each other in their nests and console each other when stressed, how they aggressively rebuff the advances of other voles that attempt to homewreck. And every time they checked, “there was oxytocin, sitting in the middle of the story, over and over again,” says Sue Carter, a behavioral neurobiologist who pioneered some of the first studies on prairie-vole bonds. The molecular pathways driving the behaviors seemed just as clear-cut: When triggered by a social behavior, such as snuggling or sex, a region of the brain called the hypothalamus pumped out oxytocin; the hormone then latched on to its receptor, sparking a slew of lovey-dovey effects.
Years of follow-up studies continued to bear that thinking out. When scientists gave prairie voles drugs that kept oxytocin from linking up with its receptor, the rodents started snubbing their partners after any tryst. Meanwhile, simply stimulating the oxytocin receptor was enough to coax voles into settling down with strangers that they’d never mated with. The connection between oxytocin and pair bonding was so strong, so repeatable, so unquestionable that it became dogma. Zoe Donaldson, a neuroscientist at the University of Colorado at Boulder who studies the hormone, recalls once receiving dismissive feedback on a grant because, in the words of the reviewer, “We already know everything that there is to know about prairie voles and oxytocin.”
So more than a decade ago, when Nirao Shah, a neurogeneticist and psychiatrist at Stanford, and his colleagues set out to cleave the oxytocin receptor from prairie voles using a genetic technique called CRISPR, they figured that their experiments would be a slam dunk. Part of the goal was, Shah told me, proof of principle: Researchers have yet to perfect genetic tools for voles the way they have in more common laboratory animals, such as mice. If the team’s manipulations worked, Shah reasoned, they’d beget a lineage of rodents that was immune to oxytocin’s influence, leaving them unfaithful to their mates and indifferent to their young—thereby proving that the CRISPR machinery had done its job.
That’s not what happened. The rodents continued to snuggle up with their families, as if nothing had changed. The find was baffling. At first, the team wondered if the experiment had simply failed. “I distinctly remember sitting there and just being like, Wait a sec; how is there not a difference?” Kristen Berendzen, a neurobiologist and psychiatrist at UC San Francisco who led the study, told me. But when three separate teams of researchers repeated the manipulations, the same thing happened again. It was as if they had successfully removed a car’s gas tank and still witnessed the engine roaring to life after an infusion of fuel. Something might have gone wrong in the experiments. That seems unlikely, though, says Larry Young, a neuroscientist at Emory University who wasn’t involved in the new study: Young’s team, he told me, has produced nearly identical results in his lab.
The explanations for how decades of oxytocin research could be upended are still being sussed out. Maybe oxytocin can attach to more than one hormone receptor—something that studies have hinted at over the years, Carter told me. But some researchers, Young among them, suspect a more radical possibility. Maybe, in the absence of its usual receptor, oxytocin no longer does anything at all—forcing the brain to blaze an alternative path toward affection. “I think other things pick up the slack,” Young told me.
That idea isn’t a total repudiation of the old research. Other prairie-vole experiments that used drugs to futz with oxytocin receptors were performed in adult animals who grew up with the hormone, says Devanand Manoli, a psychiatrist and neuroscientist at UCSF who helped lead the new study. Wired to respond to oxytocin all through development, those rodent brains couldn’t compensate for its sudden loss late in life. But the Stanford-UCSF team bred animals that lacked the oxytocin receptor from birth, which could have prompted some other molecule, capable of binding to another receptor, to step in. Maybe the car never needed gas to run: Stripped of its tank from the get-go, it went all electric instead.
It would be easy to view this study as yet another blow to the oxytocin propaganda machine. But the researchers I spoke with think the results are more revealing than that. “What this shows us is how important pair bonding is,” Carter told me—to prairie voles, but also potentially to us. For social mammals, partnering up isn’t just sentimental. It’s an essential piece of how we construct communities, survive past childhood, and ensure that future generations can do the same. “These are some of the most important relationships that any mammal can have,” says Bianca Jones Marlin, a neuroscientist at Columbia University. When oxytocin’s around, it’s probably providing the oomph behind that intimacy. And if it’s not? “Evolution is not going to have a single point of failure for something that’s absolutely critical,” Manoli told me. Knocking oxytocin off its pedestal may feel like a letdown. But it’s almost comforting to consider that the drive to bond is just that unbreakable.