Emily Dennis has spent hours, if not days, watching mosquitoes buzz around her bare, outstretched arm. Carefully, she's observed the insects land, stab their mouthparts through her skin and feed.
But if her arm is slathered with DEET — shorthand for the chemical N,N-diethyl-meta-toluamide, the active ingredient in many insect repellents — mosquitoes stay away.
"DEET works better than any other insect repellent, and despite it being around since the late 1940s, we still don't really understand why," says Dennis, a neuroscientist currently at Princeton University who endured many bug bites while studying how DEET repels insects en route to her Ph.D. at Rockefeller University.
Those bug bites paid off. In a paper published Thursday in Current Biology, she and her colleagues show that Aedes aegypti mosquitoes, common transmitters of diseases such as dengue and Zika, sense DEET through their feet, not their mouthparts. According to the authors, the finding narrows the path for future research that could potentially help scientists develop more desirable alternatives to DEET — for example, repellents that don't need to be reapplied as often as DEET.
"This is an exciting result and a very elegant study," says Walter Leal, an entomologist at the University of California, Davis, who was not involved in the work. "It's elegant because it relied only on simple behavioral experiments."
DEET works in at least two ways, according to Leslie Vosshall, a neurobiologist at Rockefeller and senior author of the study. "Mosquitoes are repelled by its smell and by its taste," she says. Previously, Vosshall's lab developed an experimental mutant variety of mosquito called orco that causes the mosquitoes to no longer be repelled by the smell of DEET.
Orco mutants don't smell DEET and will fly toward even the most DEET-steeped human, according to Vosshall. But once they land, they immediately fly away. "Not only that, but if you look deeply into their mosquito eyes, which I do all the time, it really seems like they're really freaked out," she says. This observation suggested to the researchers that mosquitoes taste DEET upon contact, either with their mouthparts or with their feet.
Yes, their feet. "Insects do this crazy and psychedelic thing, which is they taste with their feet," Vosshall says. So there were seven options for the researchers to test: six feet and the biting mouthparts.
Dennis, who spent many hours watching orco mosquitoes land on her DEET-covered skin, had a hunch. "It really didn't seem like they were touching me with their mouthparts," she says. "That made me think the legs might be important."
To test this idea, Dennis covered her arm in a latex glove with a tiny hole exposed. "Anyone who has been camping knows that if you leave even a tiny patch of skin exposed, mosquitoes will find it," she says. The opening was just wide enough for either the mouthparts or one of the legs to touch — but not both. If mosquitoes were tasting DEET with their mouthparts, they'd be repelled and wouldn't keep digging their mouthparts into the skin to feed. So Dennis shouldn't get any bites on that spot.
But she did. This told her that the mouthparts weren't tasting the DEET. Ergo: It must be the legs.
To directly test the legs, Dennis undertook what seems like the most tedious job imaginable. She carefully painted mosquito legs with a special kind of glue that disabled the taste receptors. "It was painstaking work," she says. "I enjoyed a lot of podcasts during that time."
If mosquitoes taste DEET through their legs, then smothering the legs with glue should cause orco mutants to feed on Dennis' arm as though it were DEET-free. That's precisely what happened: Dennis' arm got covered in bites. This confirmed to Dennis that mosquitoes get freaked when DEET touches their feet.
Further testing demonstrated that even one unglued leg was enough to deter mosquitoes from landing.
"We had no idea how DEET was being perceived on contact, and now we do, because of simple behavioral experiments," says Matthew DeGennaro, a neurogeneticist at Florida International University who studies mosquito genetics. He was not an author of the paper but was listed in the acknowledgments.
DeGennaro says this work could help inform the development of more-tailored alternatives to DEET. "We've narrowed it down to a tissue. Now we just have to narrow it down to a gene," he says.
DEET itself was developed in the 1940s through brute trial and error as chemists cooked up combinations of molecules to see what might work as an insect repellent. If scientists can determine which receptors in a mosquito's legs are sensing DEET, they could more easily design a DEET look-alike that repels bugs but also lasts longer or is less oily. That's still a ways off, according to Dennis. "But we've generated a lot of data that should lead to a lot more research."
And if you forget to apply bug spray before a hike in the woods this summer, Dennis has some advice based on personal experience. "Run your itchy arm under hot water" to mitigate the itchiness, she says. "That's what a lot of us mosquito researchers do."
Jonathan Lambert is a freelance science writer based in Washington, D.C. Follow him on Twitter @evolambert