Imagine an insect repellent that not only is thousands of times more effective than DEET—the active ingredient in most commercial mosquito repellents—but also works against all types of insects, including flies, moths and ants.
That possibility has been created by the discovery of a new class of insect repellent made in the laboratory of Vanderbilt Professor of Biological Sciences and Pharmacology Laurence Zwiebel and reported recently in the online Early Edition of the Proceedings of the National Academy of Sciences.
In preliminary tests with mosquitoes, the researchers found the new class of repellent—called Vanderbilt University Allosteric Agonist, or VUAA1—to be thousands of times more effective than DEET. The compound works by affecting insects’ sense of smell through a newly discovered molecular channel.
“If a compound like VUAA1 can activate every mosquito odorant receptor at once, then it could overwhelm the insect’s sense of smell, creating a repellent effect akin to stepping onto an elevator with someone wearing too much perfume—except this would be far worse for the mosquito,” says Patrick Jones, a postdoctoral fellow who conducted the study with graduate students David Rinker and Gregory Pask.
“It’s too soon to determine whether this specific compound can act as the basis of a commercial product,” Zwiebel cautions. “But it is the first of its kind and, as such, can be used to develop other similar compounds that have characteristics appropriate for commercialization.”
The discovery of this new class of repellent is based on insights that scientists have gained about the basic nature of the insect’s sense of smell during the past few years. Although the mosquito’s olfactory system is housed in its antennae, 10 years ago biologists thought it worked in the same way at the molecular level as it does in mammals. Odorant receptors, or ORs, sit on the surface of nerve cells in the nose of mammals and in the antennae of mosquitoes. When these receptors come into contact with smelly molecules, they trigger the nerves signaling the detection of specific odors.
In the last few years, however, scientists have been surprised to learn that the olfactory system of mosquitoes and other insects is fundamentally different. In the insect system, conventional ORs do not act autonomously. Instead, they form a complex with a unique co-receptor (called Orco) that is also required to detect odorant molecules. ORs are spread all over the antennae, and each responds to a different odor. To function, however, each OR must be connected to an Orco.
“Think of an OR as a microphone that can detect a single frequency,” Zwiebel explains. “On her antennae the mosquito has dozens of types of these microphones, each tuned to a specific frequency. Orco acts as the switch in each microphone that tells the brain when there is a signal.
“When a mosquito smells an odor, the microphone tuned to that smell will ‘turn on’ its Orco switch. The other microphones remain off,” he continues. “However, by stimulating Orco directly we can turn them all on at once. This would effectively overload the mosquito’s sense of smell and shut down her ability to find blood.”
Many questions must be answered before VUAA1 can be considered for commercial applications. Vanderbilt University has filed for a patent on this class of compounds and is talking with potential corporate licensees interested in incorporating them into commercial products, with special focus on development of products to reduce the spread of malaria in the developing world.
“VUAA1 opens the door for the development of an entirely new class of agents, which could be used not only to disrupt disease vectors, but also the nuisance insects in your backyard or the agricultural pests in your crops,” says Jones.