Mosquitos have pestered humans since time immemorial, ruining many a summer evening. If you live in the temperate regions of the world, a scented candle, some insect repellent and lots of clapping may be all you need to keep the critters at bay. But make no mistake, in the tropics, mosquitoes kill more people every year than any other animal, by transmitting a variety of deadly diseases, among them malaria. Mosquitoes have an exquisite sense of smell, thanks to a special neuron on their face that works much like our taste buds, and they find their hosts by following the plumes of carbon dioxide (CO2) that humans exhale. However, the same neurons in the harmless fruit fly are also affected by other odours, and sometimes they lose their ability to detect CO2. If the same was true for mosquitoes, thought Stephany Chen and her colleagues at the University of California, Riverside, USA, perhaps there is a certain smell that could make us invisible to mosquitoes and rid humanity of them and their diseases once and for all.

In a first experiment, the team placed a single mosquito in a chamber and recorded the activity of its smell neuron, which increased after a puff of CO2. Then the insect was given a scent to smell, before measuring the response of the neuron to CO2 once again. In this way, the team screened a large number of odours and found many that would either decrease the response of the neuron to CO2, increase it, or cause a sustained activation, during which time the neuron is blind to a new puff of CO2. The latter category of scents, dubbed ‘prolonged activators’, represents a promising avenue for the development of new insect repellents. Among them, butyric acid proved to be especially effective: only a 3 s whiff of the stuff would keep the mosquito's smell neuron firing continuously for over 5 min, preventing the nose-blind critters from homing in on us. Butyric acid is already part of the odour-cocktail of human sweat, and because we all emanate different amounts of it, this may explain, in part, why some of us are mosquito candy, while others escape unscathed.

There is a whole world of odours out there, some of which may have the same mosquito-repellent properties as the prolonged activator, butyric acid; but how to find them? As is often the case today, the answer is artificial intelligence. Armed with a long list of odours that were found to affect the mosquitoes’ ability to smell CO2, the team fed the data into a computer that worked out which traits of the molecules’ three-dimensional structures were common to the prolonged activators and which set them apart from all other effective odours. Then, these findings were used to train a machine-learning algorithm that, after some time, became really good at recognizing promising new candidate molecules; the software can now map the world of odours and predict which can confuse the mosquitoes’ sense of smell. It seems that the team is on the scent of a truly awesome repellent.

Among the many odours in the world, there may be a handful that cause the smell neurons of mosquitoes to fire out-of-control, and thus could cloak mankind from the insects and their deadly bite. Butyric acid, for instance, works wonders to make mosquitoes nose-blind, but the odour is not a particularly lovely one: it smells like rancid butter. Before you find yourself wearing it to your next garden party, maybe wait and see whether artificial intelligence will yield a less pungent solution.

S. T.
Prolonged activation of carbon dioxide-sensitive neurons in mosquitoes
Interface Focus
. doi:10.1098/rsfs.2020.0043