The way in which DEET, the familiar insect repellent, actually works has finally been discovered. Scientists at the University of California, Riverside have identified neurons in Drosophila antennae that express a highly conserved, DEET-sensitive olfactory receptor, Ir40a. The scientists observed that flies in which these neurons are silenced, or Ir40a is knocked down, lose avoidance to DEET.
DEET, which is also known as N,N-diethyl-m-toluamide, has been in use for over 65 years and remains effective, but it has several drawbacks. It is capable of dissolving plastics and nylon. It has been reported to inhibit acetylcholinesterase, an enzyme important in the mammalian nervous system. And it is unaffordable in Africa and other parts of the world where hundreds of millions suffer from insect-transmitted diseases.
Repellents that might have succeeded DEET were never developed, mainly because the receptor in insects for DEET remained unknown. According to Anandasankar Ray, who led the research team at Riverside, “Without the receptors, it is impossible to apply modern technology to design new repellents to improve upon DEET.” Also, new chemicals require costly tests to determine safety for human use.
Besides identifying the DEET-detecting receptors, Ray and his colleagues identified three safe compounds that mimic DEET and could one day be used to prevent the transmission of deadly vector-borne diseases such as malaria, dengue, West Nile virus, and yellow fever. Ray and his colleagues published their work online, in Nature on October 2 (“Odour receptors and neurons for DEET and new insect repellents”).
“Our three compounds...do not dissolve plastics,” Ray said. “They are approved by the FDA for consumption as flavors or fragrances, and are already being used as flavoring agents in some foods. But now they can be applied to bed-nets, clothes, and curtains.”
The researchers engineered Drosophila melanogaster in such a way that neurons activated by DEET glowed fluorescent green. Following the glow, the researchers found activated receptors lining the inside of a poorly studied region of the antenna called the sacculus.
Using chemical informatics, Ray’s lab screened more than 440,000 compounds against the DEET receptor to identify substitutes. A computer algorithm the team developed predicted over 100 natural DEET substitutes, including three strong mosquito repellents—the compounds previously approved as food additives.
“All three compounds activated the same antennal cells in flies as DEET,” Ray said. “What’s really encouraging is that some [DEET substitutes] may be affordable to produce in large quantities."