clipped from online.wsj.com

• SEPTEMBER 1, 2009

Finding Smells That Repel

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By SHIRLEY S. WANG

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If you're one of those people whom mosquitoes tend to favor, maybe it's because you aren't sufficiently stressed-out.

Insects have very keen powers of smell that direct them to their targets. But for researchers trying to figure out what attracts or repels the pests, sorting through the 300 to 400 distinct chemical odors that the human body produces has proved daunting.

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Now scientists at Rothamsted Research in the U.K. have been making headway at understanding why some people can end up with dozens of bites after a backyard barbecue, while others remain unscathed. The researchers have identified a handful of the body's chemical odors—some of which may be related to stress—that are present in significantly larger concentrations in people that the bugs are happier to leave alone. If efforts to synthesize these particular chemicals are successful, the result could be an all-natural mosquito repellent that is more effective and safer than products currently available.

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"Mosquitoes fly through an aerial soup of chemicals, but can home in on those that draw them to humans," says James Logan, a researcher at Rothamsted, one of the world's oldest agricultural-research institutions. But when the combination of human odors is wrong, he says, "the mosquito fails to recognize this signal as a potential blood meal."

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The phenomenon that some people are more prone to mosquito bites than others is well documented. In the 1990s, chemist Ulrich Bernier, now at the U.S. Department of Agriculture's Agricultural Research Service, began looking for what he calls the "magic compounds" that attract mosquitoes. His research helped to show that mosquitoes are attracted to humans by blends of common chemicals such as carbon dioxide, released from the skin and by exhaling, and lactic acid, which is present on the skin, especially when we exercise. But none of the known attractant chemicals explained why mosquitoes preferred some people to others.

Rothamsted's Dr. Logan says the answer isn't to be found in attractant chemicals. He and colleagues observed that everyone produces chemicals that mosquitoes like, but those who are unattractive to mosquitoes produce more of certain chemicals that repel them.

Misguided Mosquitoes

"The repellents were what made the difference," says Dr. Logan, who is interested in the study of how animals communicate using smell. These chemicals may cloud or mask the attractive chemicals, or may disable mosquitoes from being able to detect those attractive odors, he suggests.

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Besides delivering annoying bites, mosquitoes cause hundreds of millions of cases of disease each year. As many as 500 million cases of malaria are contracted globally each year, and more than one million people die from it, according to the Centers for Disease Control and Prevention. Mosquitoes can also spread West Nile virus, dengue fever, yellow fever and other illnesses.

Currently the most effective repellents on the market often contain a chemical known as DEET, which has been associated in some studies with potential safety concerns, such as cancer and Gulf War syndrome. It also damages materials made of plastic. The federal Environmental Protection Agency has determined that DEET, when used as directed, is safe.

The Rothamsted team set out to get the mosquitoes' viewpoint. The researchers separated human volunteers into two groups—those who were attractive to mosquitoes and those who weren't. They then put each of the volunteers into body-size foil bags for two hours to collect their body odors. Using a machine known as a chromatograph, the scientists were able to separate the chemicals. They then tested each of them to see how the mosquitoes responded. By attaching microelectrodes to the insects' antennae, the researchers could measure the electrical impulses that are generated when mosquitoes recognize a chemical.

Dr. Logan and his team have found only a small number of body chemicals—seven or eight—that were present in significantly different quantities between those people who were attractive to mosquitoes and those who weren't. They then put their findings to the test. For this they used a so-called Y-tube olfactometer that allows mosquitoes to make a choice and fly toward or away from an individual's hand. After applying the chemicals thought to be repellant on the hands of individuals known to be attractive, Dr. Logan found that the bugs either flew in the opposite direction or weren't motivated by the person's smell to fly at all.

The chemicals were then tested to determine their impact on actual biting behavior. Volunteers put their arms in a box containing mosquitoes, one arm coated with repellent chemicals and the other without, to see if the arm without the coating got bitten more.

Significant Repellency

The group's latest paper, published in March in the Journal of Medical Entomology, identified two compounds with "significant repellency." One of the compounds, 6-methyl-5-hepten-2-one, is a skin-derived compound that has the odor of toned-down nail-polish remover, according to George Preti, an organic chemist at the Monell Chemical Senses Center in Philadelphia, who is involved in a separate line of research into insect-biting behavior. The other, identified in the paper as geranylacetone, has a pleasant odor, though there is some question about whether the chemical is formed by the human biochemical process or is picked up in the environment, Dr. Preti says.

Dr. Logan declined to comment about the specific chemicals because of proprietary concerns. He says the findings have been patented and the group is working with a commercial company to develop the compounds into a usable insect repellent. One issue that still needs to be resolved: how to develop a formulation of the repellent chemicals that will stay on the skin, rather than quickly evaporating as they do naturally. The hope is to get a product to market within a year or two, he says.

Some of the chemicals researchers identified are believed to be related to stress, Dr. Logan says. Previous research has shown that these particular chemicals could be converted from certain other molecules and this could be as a result of oxidation in the body at times of stress, he says. However, it's not clear if the chemicals observed by the Rothamsted researchers were created in this way, and research is continuing to answer this and other questions.

Dr. Logan suggests that mosquitoes may deem hosts that emit more of these chemicals to be diseased or injured and "not a good quality blood meal." Proteins in the blood are necessary for female mosquitoes to produce fertile eggs, and Dr. Logan says it might be evolutionarily advantageous for mosquitoes to detect and avoid such people.

Other Research

Other research includes an effort by scientists at the University of California, Riverside, who published a paper in the journal Nature last week identifying a recently discovered class of molecules that inhibit fruit flies' and mosquitoes' ability to detect carbon dioxide. Mosquitoes can detect carbon dioxide emissions from long ranges, so turning off the ability to detect the gas, perhaps by releasing the inhibiting molecules into the environment, may be a way of keeping the bugs at bay, the researchers suggest. Another team, at the Monell Chemical Senses Center, is launching a study into whether the taste of human skin and blood are related to the insects' interest in biting certain individuals.