When Conor McMeniman was growing up in the subtropics of Queensland, Australia, he was constantly pestered by mosquitoes. And like many of his fellow Aussies, he bought into long-held fables about the insects—that they're drawn to backyard barbecues and hiking trails in search of people with particularly delectable blood or skin.
Today, McMeniman, 41, knows better. He's an assistant professor of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health, where he runs a lab specializing in mosquito-borne illnesses. Studies have already established that mosquitoes track their human prey via body odor in the form of volatile organic compounds, or VOCs, which, combined with the emission of carbon dioxide that we exude, provide "a bouquet on the order of 300 to 500 different chemicals," McMeniman explains.
But earlier this year, he co-authored a study, the first in a series, that begins to unlock the mystery of why mosquitoes, especially those carrying deadly diseases, are attracted to specific human scents and repelled by others.
Here's what scientists already knew: Mosquitoes use a variety of cues to home in on their targets. Odor distinguishes people from other animals, and some mosquitoes have evolved to seek out the bouquets McMeniman mentions. Many also carry debilitating diseases, including dengue, yellow fever, malaria, and the Zika and West Nile viruses, killing more than 700,000 people a year.
Why do these miniature vampires lust after human blood in particular? Because our blood is protein-rich, providing female mosquitoes, the ones that bite, with vital nutrients. "And the amino acids, once they've broken down, signal egg production," McMeniman says. "So, the blood is used as both an energy source and for reproduction."
Until now, olfactory tests for mosquito preferences were conducted indoors, on a very small scale, so as not to put humans at risk. These tests used scent-laden lures such as sweaty socks, T-shirts, and glass beads rolled in a human hand, McMeniman explains. What's still not very well understood he says, "[are] the emission rates of these different compounds in the air and also how much individual humans vary in their scent chemistry."
The challenge, then, was to fabricate a lab environment that came as close to real life as possible and was large enough that scientists could better understand the mosquitoes' preferences while also protecting human subjects from their bite.
For this study, the team focused specifically on Anopheles gambiae, the primary carrier of malaria throughout sub-Saharan Africa. Like most mosquitoes, which avoid direct sunlight and the risk of dehydration, they hunt their prey at night, while people are either sleeping or engaging in outdoor activities.
Partnering with the Macha Research Trust, a longtime Hopkins research affiliate with a facility located in a remote part of Zambia, McMeniman's team planned and built an outdoor testing ground, which took several years to complete. Its centerpiece is a screened-in, open-air "flight cage," which, at 4,300-square-feet, is about the size of an ice rink. Surrounding the cage, at a distance of roughly 50 feet, are one-person tents, each connected to the facility by a long duct. A fan blows the human subject's scent and CO2 emissions into the cage and onto an aluminum plate warmed to 95 degrees Fahrenheit, mimicking human skin temperature to entice the insects.
Over six nights in April 2022, 200 lab-bred and therefore disease-free Anopheles gambiae mosquitoes were released into the cage at 8 p.m. Two hours later, six human subjects entered their tents, and, while they slept, cameras observed the mosquitoes as they flocked to their plates of choice to satisfy their bloodthirsty palates.
Of the six subjects, McMeniman says, the tastiest, the one that drew the most mosquitoes consistently, emitted "a scent signature predominated by a class of molecules called carboxylic acids," which are compounds found in the sweat and oily residue secreted by humans as a natural moisturizer. While those same acids are associated with unpleasant odors—Limburger cheese, for example—"normally, they are not perceptive to the human nose," he says. "But the mosquito has a much more powerful sense of smell, one more attuned to these molecules."
Their least attractive subject, he adds, was someone whose bouquet was lacking carboxylic acids and suffused with eucalyptol, "a plant-derived chemical found in a wide variety of plants, in herbs and spices," he reports. "It's also found in toothpaste and mouthwash."
The reasons for these levels of compounds are, as yet, undetermined. The aim of the study, the first in a series, was to test a much larger-scale facility than has ever been used before and, working from the premise that mosquitoes are drawn to human odor, establish baseline findings. Follow-up studies, conducted over the next two wet seasons in Zambia, will expand these experiments to include a total of 120 participants profiled for a broader mix of VOCs. Factors like diet, heart rate, blood type, skin temperature, and CO2 emissions will be tracked.
The team will also examine ways mosquitoes might be repelled. While the public consensus is that certain soaps, sprays, and methods of hygiene keep the pesky, and sometimes dangerous, insects at bay, the Hopkins team will look closely at their subjects' metabolisms as well as the bacteria living on their skin and inside their mouths, all of which influence a person's odor, McMeniman says. They also hope to build a similar facility in Maryland to test for disease-carrying mosquitoes native to the United States.
The end goal of these studies is to use the test results to devise ways to prevent the contraction of deadly diseases. One may be to mask the most attractive odors by "developing new molecules that scramble a mosquito's sense of smell or olfactory coding to make a person smell not quite right to them," McMeniman says.
Another may be to develop a device to serve as a decoy. "A large focus for our lab," he adds, "is to mimic the scent profiles of highly attractive humans to use them as baits for a mass trap."
Think gigantic bug light.
"If you could make a blend that smells really good," McMeniman says, "then it becomes possible to do mass trapping for control of disease."