Mutant Mosquitoes

June 2, 2013, 3:22 p.m.

A team of neurobiologists has engineered a species of mosquito to lack a gene responsible for sniffing out humans. It doesn't seem to stop them heading straight for their fleshy luncheon (unfortunately), but the team believes it is the key to creating full-proof insect repellants.

Leslie Vosshall, neurobiologist at The Rockefeller University, discovered the genes that help insects sense and perceive scent and carbon dioxide -- two markers that draw them toward prey, usually indiscriminately. However, some species actually favour humans, and unfortunately two of those, Aedes aegypti and Anopheles gambiae, carry deadly diseases -- dengue and yellow fever for the former, and malaria for the latter. Although carbon dioxide and things like body temperature are thought to contribute to that attraction, it's clear that scent has a lot to do with it.

"Specific host odours probably drive this strong preference because other attractive cues, including body heat and exhaled carbon dioxide (CO2), are common to all warm-blooded hosts," points out Vosshall and her team in a paper on their experiment, published in Nature.

Focusing on the olfactory cues, the team engineered A. aegyptimosquitoes to lack the gene known as orco. According to Vosshall's lab page, the gene is "unique in being expressed in nearly all olfactory neurons"; the ubiquitous gene expresses a protein that plays a part in generating odorant receptors in most insects. To rid the mosquito of the gene, the team inserted zinc-finger nucleases (engineered restriction enzymes) into mosquito embryos and bred those mutant offspring (that showed less activity in odour-related neurons) lacking the gene. 

When left in a room with a human and a guinea pig, the mutated mosquitoes appeared to no longer have a preference for either in particular. That's in spite of the other contributory factors presumed to contribute to the human attraction, such as carbon dioxide -- the test subjects were obviously still allowed to breath -- and body temperature, still being present.

"By disrupting a single gene, we can fundamentally confuse the mosquito from its task of seeking humans," said Vosshall in a statement. Since the mosquito did still go to both test subjects, it's unclear exactly what the orco gene is telling it -- i.e. does it help them perceive the scent of animals as a deterrent and that of humans as pleasant? 

Experimentation with other scents showed that its ability to smell was well and truly befuddled -- for instance, it could not identify honey (which it loves) from glycerol. 

However, when volunteers were slathered in N,N-diethyl-meta-toluamide (Deet), a popular repellant used for decades, the mosquitoes did not appear to be bothered. They flew to an arm covered in the substance as readily as to one lacking it. After landing they would however soon fly off, suggesting Deet's benefits do not solely lie in its scent -- "olfactory- and contact-mediated effects of Deet are mechanistically distinct," write the authors.

A February study published by the London School of Hygiene and Tropical Medicine did however indicate that some strains of A. aegyptimight be developing a resistance to the repellant. Mosquitoes that were exposed to a person who had administered Deet were initially put off, but after a few hours they would approach more readily. After attaching electrodes to their antennae, they found that the mosquito's tiny receptors were no longer picking up the chemical as accurately. Vosshall did show that the insects, though able to initially land on the volunteer's arm, were ultimately repelled by Deet though.

The team is hoping to use what it has perceived as a helpful scrambling of the mutated mosquito's senses to its advantage, generating a repellant that throws the mosquito off-course rather than breeding out mosquitoes carrying the orca gene. Given the ubiquity of the gene among the insect kingdom, it's likely to be of significant help in generating life-saving repellants. What will be key is uncovering what instructions the orco genes are actually delivering, and whether what they are dictating to the odorant receptors is good or bad?


Elsewhere in the world this month, an Egyptian textile chemistry PhD claims to have engineered a fabric that not only repels mosquitoes, but kills them if they dare to remain onboard. He wouldn't reveal the secret behind the patented formula, but his tactics are in stark contrast to those of Laurence Zwiebel's, a molecular entomologist from Vanderbilt University who left Nature with these noble words to ponder: "We're not looking to kill these insects, per se, we just want them to feed on something else." Guinea pigs beware.

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