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Waiting for Next-Gen Anti-Mosquito Chemicals with Bated Breath

Novel natural compounds may lead to safe and inexpensive repellents that undercut skeeters' ability to sense their human prey



ISTOCKPHOTO/CHRISTOPHERBADZIOCH

With every breath you take, they'll be watching you—and anticipating their next blood feast. It's true—mosquitoes get dinner signals from your exhaled carbon dioxide, along with your body heat and moisture. But what if there was a way, other than holding your breath, to keep a mosquito from detecting the giveaway gas? Researchers on the hunt for a cheaper, safer and more environmentally friendly mosquito repellent recently happened on a clue for just such a strategy.

Anandasankar Ray, an entomologist at the University of California, Riverside, has been on the lookout for novel chemicals to lower the prevalence of mosquito-borne disease. His motivation is personal: "Growing up in India, I was exposed to many tropical neglected diseases; I've had malaria, my wife has had dengue," says Ray, who is the co-author on a study of the new approach published today in the journal Nature. (Scientific American is part of the Nature Publishing Group.) "We wanted to understand the olfactory mechanisms underlying how mosquitoes are attracted to human beings."

At the same time, he and his graduate student, Stephanie Lynn Turner, were also pursuing answers to a more basic biology question: Why did drosophila (fruit flies) avoid carbon dioxide emitted by fellow flies as a warning of danger, but then flock toward fermenting fruit that releases the same compound?

On further investigation into this paradox, the researchers found that fruit simultaneously emits other compounds that block a fly's ability to detect carbon dioxide. "These two areas we previously thought of as disparate converged in this paper," Ray notes. "The moment we had a clue about what was happening with drosophila and fruit—that specific odor components in fruit could block carbon dioxide receptors efficiently—we immediately realized we were on to a solution for our second motivation."

One of the few sensory receptors shared among insects is that for carbon dioxide, including the majority of bloodsucking bugs that pass on diseases—from mosquitoes that carry the West Nile Virus, yellow fever, dengue and malaria to tsetse flies that harbor sleeping sickness. So Ray and Turner began investigating odorants related to those emitted from ripening fruit that could inhibit carbon dioxide-detection machinery in mosquitoes. Although the team continues to screen hundreds of potential compounds, so far two have proved promising: 1-butanal and 1-hexanol.

In addition to these compounds' efficiency, Ray highlights the minimal concentrations and complications involved in producing the new repellent: The amount of chemical required is relatively small—about 1 percent, compared with several times that for DEET. Further, the chemicals themselves are not complicated to manufacture and are available through conventional sources. "From both perspectives, this adds up to a viable tool in tackling the problems like that of malaria in Africa," Ray says. He also believes these advantages will keep costs relatively low. 

Other experts in the field of mosquito olfaction also recognize the potential. "This work clearly speaks to the idea that you can target these olfactory-driven sensors that lead to olfactory-driven behaviors, and perhaps misdirect insects away from crops and people—critical issues in terms of global health and agriculture," says Laurence Zwiebel, a professor of biology and pharmacology at Vanderbilt University who was not involved in the research. "I believe that we can find natural inhibitors of odorant receptors that mosquitoes use to do the things that we don't like that they do."

But there is much work to be done before entomologists can halt the deadly mosquitoes. In addition to the hurdle of creating the perfect chemical concoction, the most effective method of their application is still unclear. "In order to find out how we can apply them and in what form—whether as an aerosol, lotion or simply as a diffusing air source—we need to do a lot more experiments," says Ray, who is currently running tests in wind tunnels, mosquito flight tunnels and using video microscopy. Because exhaled carbon dioxide dissipates, Ray thinks some of the inhibitory chemicals may be useful as "area masking agents," protecting an entire U.S. backyard or hut in Africa.

Also, the compounds' effects on human health have yet to be tested, although Ray is optimistic because many of his current candidates are already approved for fragrances and flavors. In the end, "it's a matter of picking and choosing the safest for human beings and the safest for the environment, while minimizing the quantities and maximizing their effect," Ray explains. With the help of a grant from the Bill & Melinda Gates Foundation as well as anticipated collaborations with private companies to try to come up with a viable product, Ray predicts it will be another five years or so before the novel chemicals will be utilized in the field.

"There's an enormous time frame from discovery to development to deployment. Regulatory issues, the economics of bringing products to market, and variances of international and domestic politics all come into play with this effort," Zwiebel says. "I do believe this will translate into novel intervention strategies. But I'm just not sure how long it will take to get to marketplace—and to the developing world where it is so very critical…. We're only just scratching the surface of the development process." Hopefully, with some continued scratching and sniffing in the lab, the illnesses—and itching—of millions can eventually be relieved.

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