It's a breakthrough in the fight against disease-carrying mosquitoes. Researchers have found a chemical that disables the part of the insect's brain that smells humans. Future bug repellents based on the compounds could give people an invisibility cloak against the winged pests. We talked to a scientist who worked on the discovery to find out more.

There are three main ways that mosquitoes zero in on their targets. The strongest mosquito attractant is carbon dioxide (CO2), which the insects can detect from a distance of up to 20 to 30 meters. "The reason mosquitoes and other blood-feeding insects have evolved to detect CO2 is because every living vertebrate is going to produce a lot of CO2 as turbulent plumes," said Anandasankar Ray, an entomologist at the University of California, Riverside. "It doesn't just dissipate; the prevailing wind will carry it almost like cigarette smoke gets carried away."


At closer range, mosquitoes can sense different odors that are emitted from the skin (human skin odor is mostly the byproduct of skin microbes, which break down sweat to produce smelly volatiles). Finally, mosquitoes can detect body heat. Some research has also suggested that mosquitoes are attracted to certain blood types, which may be mediated by different odor molecules, but the evidence for this idea is not robust, Ray told io9.


The Carbon Dioxide Conundrum

Given mosquitoes' remarkable ability to detect CO2 from a great distance, scientists have focused on determining just how, exactly, the insects can sense the gas, in hopes of someday blocking the ability. What it boils down to, they found, is a class of olfactory sensory neurons called cpA, which are housed in the mosquitoes' maxillary palps, a type of sensory organ between the antennae near the mouth. In 2011, Ray and his colleagues discovered that they could use certain chemical odors to overstimulate the cpA neurons, and disrupt mosquitoes from detecting CO2.

"We then started wondering what would happen if the [CO2-blocked] mosquitoes would come closer to us and go towards our feet or arms," Ray said. Even though the mosquitoes can't detect people from the carbon dioxide on their breath, they could still sense skin odor, allowing them to find their prey. So the team, as well as other research groups, decided to pinpoint receptors that pick up on skin odors.


Experiments have demonstrated that skin odor alone can draw in mosquitoes, and scientists found that some odors did activate certain receptors in mosquito antennae. But, strangely, researchers couldn't tie the activation of these receptors to the mosquitoes' attraction behavior. In every case, the insects' CO2 receptors also needed to be activated with carbon dioxide to elicit the attraction behavior. This left everyone scratching their head, trying to figure out why activating just the antennae receptors didn't work. "At that point we hit a roadblock," Ray said.

Sensing Human Skin Stench

Turns out, the answer to the problem lied in the CO2-sensitive neurons. A graduate student realized that the only known olfactory neurons definitively shown to be involved in mosquito host-seeking behavior were the cpA neurons in the palps. So what if the cpA neurons detected not only CO2, but also skin odors?


To find out, Ray and his colleagues collected a skin odor blend and put it onto mosquito palps, while they recorded the activity of the cpA neurons (in the absence of CO2). The neurons fired like crazy, demonstrating that the cpA neurons can detect skin odor. Next, the researchers sought to identify specific components from the blend that activated the neurons. "Our grad student was able to identify about a dozen or more odors from skin that are activating the CO2-receptor neurons very strongly," Ray said.

Though the neurons were detecting the skin odors, the researchers had yet to show that the receptor is important for attraction behavior. "In order to do that, we designed a novel chemical genetic strategy," Ray said. The team exposed mosquitoes to a chemical called butyryl chloride, which shut down the insects' CO2-receptor neurons. They dosed small beads with human foot odor by placing them in dirty socks, and then put the beads and mosquitos into an experimental wind tunnel.


About 85 percent of the treated mosquitoes were unable to find and land on the stinky beads. By comparison, only 35 percent of untreated mosquitoes didn't make it to the beads.

"This established that the CO2 receptor is the central sensor of human beings," Ray said. "It not only smells CO2 in our breath, but it's also responsible for smelling odor from our skin."


Blocking Our Smell

Finally, the researchers decided to see if they could identify specific chemical odors that inhibit or strongly activate the cpA neurons — such chemicals could somebody be used in repellents or traps. Though they found important chemicals in their previous study, the compounds they discovered weren't really suitable for use around humans because of their pungent smell and certain health safety concerns, Ray said. The team also wanted to find chemicals that are relatively cheap, so that poorer countries dealing with mosquito-related diseases can use the chemicals, too (the repellent DEET isn't widely used in certain areas of Africa and Asia mainly because of its high cost).

They designed a computer algorithm to automatically screen about half a million compounds for structural features similar to the activators and inhibitors they previously found. The algorithm predicted thousands of chemicals, which the researchers further narrowed down based on smell, cost and safety. They experimentally tested some of them and showed that they worked as expected (blocked CO2 and odor detection, or lured mosquitos in to a trap), including an inhibitor that smelled like rum and raisins.


Importantly, the research shows that blocking mosquitoes' detection system — both CO2 and skin odor — is simpler than previously believed because it requires disrupting a single class of olfactory sensory neurons with just one chemical. Ray isn't sure what kind of repellents or traps the chemicals could make, but suggests that there are many possible avenues to go down. For example, the chemicals could be released in skin patches, or applied directly to the skin or clothes by way of a spray. "One idea is to try to see if we can create an invisibility cloak around a number of people and make zone free of mosquitoes," Ray said. "This could work by maybe evaporating some of these odors in a large space."

The team is now interested in trying to understand what makes some people more attractive to mosquitoes than other people, and perhaps figure out what role blood type really plays in the matter. They also want to determine if there are other neural pathways that are involved in the insects' detection abilities.


"Ultimately, we want to apply the full potential of modern neuroscience research and modern neuroscientific approaches to create the next generation of insect manipulators, and utilize that in tackling the spread of deadly diseases," Ray said.

Read about the research over in the journal Cell.

Top image via John Tann/Flickr. Inset images via Ray Lab, UC Riverside and Genevieve Tauxe.