See published paper in PNAS (Embargoed lifted at 2 p.m. Pacific Standard Time, Aug. 18, 2008)
Link to video from Walter Leal lab
Listen to BBC interview of Walter Leal from Web site or link directly to: MP3 or WAV.

DAVIS—Spray yourself with DEET, and you'll repel mosquitoes, but why? It's not because DEET jams their sense of smell; it's because they dislike the smell of the chemical repellent intensely, researchers at the University of California, Davis have discovered in groundbreaking research published today (Monday, Aug. 18).

“We found that mosquitoes can smell DEET and they stay away from it,” said noted chemical ecologist Walter Leal, professor of entomology at UC Davis. “DEET doesn't mask the smell of the host or jam the insect's senses. Mosquitoes don't like it because it smells bad to them.”

DEET's mode of action or how it works has puzzled scientists for more than 50 years. The chemical insect repellent, developed by scientists at the U.S. Department of Agriculture and patented by the U.S. Army in 1946, is considered the “gold standard” of insect repellants worldwide. Worldwide, more than 200 million use DEET to ward off vectorborne diseases.

Scientists long surmised that DEET masks the smell of the host, or jams or corrupts the insect's senses, interfering with its ability to locate a host. Mosquitoes and other blood-feeding insects find their hosts by body heat, skin odors, carbon dioxide (breath), or visual stimuli. Females need a blood meal to develop their eggs.

Entomologist James "Jim" Miller of Michigan State University praised the work as correcting “long-standing erroneous dogma.”i

Said Miller: "For decades we were told that DEET warded off mosquito bites because it blocked insect response to lactic acid from the host -- the key stimulus for blood-feeding. Dr. Leal and co-workers escaped the key stimulus over-simplification to show that mosquito responses -- like our own -- result from a balancing of various positive and negative factors, all impinging on a tiny brain more capable than most people think of sophisticated decision-making.”

“This new work corrects long-standing erroneous dogma, and shows that recent work on DEET mode-of-action published in the flagship journal, Science, apparently was flat-out wrong,” Miller said. “One of the great attributes of science is that, over time, it is self-correcting."

Leal said previous findings of other scientists showed a “false positive” resulting from the experimental design.

The UC Davis work, “Mosquitoes Smell and Avoid the Insect Repellent DEET,” is published in the Aug. 18 edition of the Proceedings of the National Academy of Sciences (PNAS).

Mosquitoes detect DEET and other smells with their antennae. Leal and researcher Zain Syed discovered the exact neurons on the antennae that detect DEET (N,N-diethyl-3-methylbenzamide). These neurons are located beside other neurons that sense a chemical, 1-octen-3-ol, known to attract mosquitoes.

“I was so delighted when I first encountered the neuron that detects DEET, a synthetic compound,” said Syed. “I couldn't believe my eyes because it goes against conventional wisdom so I repeated the experiment over and over until we discussed the findings in the lab.”

The UC Davis investigators set up odorless sugar-feeding stations, some containing DEET, and found that DEET actively repelled them. The mosquitoes they used were Culex quinquefasciatus, also known as the Southern house mosquito. The mosquito transmits West Nile virus, St. Louis encephalitis, and lymphatic filariasis, a disease caused by threadlike parasitic worms.

“Despite the fact DEET is the industry standard mosquito repellent, relatively little is known about how it actually works,” said UC Davis research entomologist William Reisen. “Previous studies have suggested a 'masking' or 'binding' with host emanations.  Understanding the mode of action is especially important because DEET is used as the standard against which all other tentative replacement repellents are compared.

Reisen said that Leal and Syed “have performed an exhausting series of sophisticated, directed, yet straight-forward experiments to determine that the mode of action of DEET is mostly due to the response of a specific sensilla to DEET.  Although there may be some host odor 'binding,' the critical finding that DEET inhibited sugar feeding clearly showed that mosquitoes of both sexes detected DEET and were repelled, even without a host being present.”

Said Major Dhillon, president of the American Mosquito Control Association and district manager of the Northwest Mosquito and Vector Control District, Riverside:  “It certainly is a breakthrough. In the future, this new knowledge can be incorporated into developing new repellents and may be in control strategies for Culex quinquefasciatus and other mosquitoes.”

Research chemist Uli Bernier of the Mosquito and Fly Research Unit, USDA Agricultural Research Service, described the UC Davis study as “an excellent explanation.” Bernier, who studies how repellents impact mosquitoes' feeding behavior, said the Leal-Syed work  “presents as a very logical basis to help us understand how DEET is perceived by the mosquitoes, and this work provides an excellent explanation to link physiological processing within the mosquito to the (macroscopic) behavioral response that we observe in laboratory bioassays with this repellent."

Leal, a past president of the International Society of Chemical Ecology, received the 2007 Silverstein-Simeone Lecture Award for his innovative research on how insects detect smells and communicate within their species. He is a former chair of the UC Davis Department of Entomology.

Resources:
Download high-resolution photo, Culex quinquefasciatus (Kathy Keatley Garvey, UC Davis Department of Entomology)
Download high-resolution photo of Culex quinquefasciatus on arm (Kathy Keatley Garvey, UC Davis Department of Entomology)
Download high-resolution spray photo http://169.237.77.3/news/images/culexquinquefasciatuspnas.jpg(Kathy Keatley Garvey, UC Davis Department of Entomology)
PNAS paper (PDF)
Science article (March 2008) referred to by James Miller