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Since World War II, people worldwide have liberally applied N,N-diethyl-m-toluamide, better known as DEET, to ward off blood-feeding insects that can transmit malaria and other diseases. But no one knew exactly how the most commonly used active ingredient in topical bug repellants worked until now. Leslie B. Vosshall and colleagues at Rockefeller University report that DEET inhibits certain mosquito and fruit fly olfactory receptors (Science, DOI: 10.1126/science.1153121). Previous work by other researchers had shown that DEET affects insects' ability to sniff out human odors, such as those caused by lactic acid. But Vosshall and colleagues are the first to pinpoint DEET's molecular targets: olfactory receptors that form a complex with a coreceptor called OR83b. To find these receptors, the researchers combined a genetic approach with an in vitro reconstitution of insect odorant receptors. Knowing how DEET affects receptors could lead to new insect repellents that, for example, could be safely used on young children. "We can use high-throughput, small-molecule screening to identify novel compounds that have greater efficacy and selectivity than DEET," Vosshall says.
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