The Mice That Roared

Ted and Valina Dawson of Johns Hopkins University were doing the kind of scientific gruntwork the recruiters don't warn about: breeding mice. They started with five special mice lacking the gene needed to make nitric oxide (NO), a little molecule best known as an air pollutant but recently found to exist in the brain, too, where it carries chemical signals from neuron to neuron. The Dawsons were studying NO's role in brain damage caused by stroke. But last year, when they arrived at their lab on workday mornings, they often found that one or two mice were dead. At first the scientists suspected heart attacks. But when they looked closely they save that the dead had not gone gentle into the good mousy night: they had been killed by cage mates. The mutant mice were sexual aggressors, too: when put into cages with females, "the females would cower, sit and scream for hours," says Hopkins neuroscientist Randy Nelson. "But still the males kept mounting them."

The researchers bagged the stroke research. With Hopkins's Solomon Snyder, they designed experiments to examine how the lack of NO turned animals that were downright mousy into serial killers and rapists. They slipped a normal male mouse into a cage with a mutant male; the mutant relentlessly launched three times more attacks than did a normal male facing an intruder, the scientists reported last week in the journal Nature. The attacks didn't stop even when the victim "surrendered" by lying on its back. The scientists then caged a mutant male with a female who was not in estrus; normal males gave up, but the mutant mounted the screaming female for hours. Earlier studies also found "knockout" mutations (so called because a gene is KO'd) that make mice hyper aggressive. But "the extent of the behavioral change we see here," says Snyder, "is totally unprecedented."

How can the absence of one brain chemical produce such psychopathic mice? The best guess is that "nitric oxide may be the neurotransmitter that puts a brake on some behaviors" such as sexual and other aggression, says Snyder. Once the knockout mice start fighting, they don't stop. The mutant "doesn't get the message of surrender or disinterest," says Snyder. Female mice showed no such aggression. While that may simply prove once again females' moral superiority, it may instead be because female mice fight only to protect newborns.

At this point scientists usually caution that their findings are years away from being relevant to people. But curiously, given the passions aroused by any whisper of a link between genes and violence, the authors declare that NO may shed light on "the biological determination" of "sexual and aggressive behaviors. . . in humans." Snyder goes further. "What we might have here is an example of serious criminal behavior that can be explained by a single gene defect," he says. Which leaves other scientists aghast. "Remember, these are knockout mice, not knockout men," says neuroscientist Craig Ferris of the University of Massachusetts. "But I can see the headline now: ARE SERIAL RAPISTS MISSING THIS GENE?" Ferris finds it plausible that some patients hospitalized for uncontrollable rage have a genetic predisposition to violence-even, perhaps, an NO deficit. But that explains almost nothing about garden-variety violence. And it doesn't mean that providing NO would cure men given to violent rage: lack of NO may have irreversibly changed the wiring of their brains, and there's no guarantee that NO is the only, or even the primary, reason for their aggression. When it comes to explaining criminal aggression, it's way too early to just say NO.

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