Studying Ant “Noses” Could Lead to Better Bug Repellents

The new class of repellents, called “excito-repellents,” is similar to “getting on an elevator with someone who’s put on way too much perfume”

This false-color image depicts various compounds that ants smell to detect where their nestmates stand in the colony's social hierarchy. Keith Wood & Jeremy Teaford, Vanderbilt University

Ants are known for being able to heft up to 50 times their own body weight, but new research shows their sense of smell might be even more formidable than their strength. Like most insects, “ants see the world through their noses,” says Laurence Zwiebel, a professor of biological sciences and pharmacology at Vanderbilt University. Unlike other insects that only have 70 or so odor receptors, ants use over 400 to navigate and interact with one another. Now, Zwiebel and his colleagues are creating a Rosetta stone of insect language they hope to co-opt to refine new, highly effective insect repellents.

In a new study published in Proceedings of the National Academy of Sciences, Zwiebel and his team describe how ants use scent to organize their complex social behavior. In another study in press at Cell, they show just how critical ant olfaction is by taking away their sense of smell and watching mayhem ensue. When an ant finds a good food source, they mark the trail with pheromones so other ants in their colony can tag along and forage more effectively. They also coat themselves in smelly chemicals that differentiate workers from nurses and allow ants to recognize rival colonies. Take away their ability to sense those chemical smells and things fall apart. “They lose their ability to interact with each other, they wander off and they start behaving badly,” he says.

By teasing apart which chemicals interact with specific odor receptors and how they make ants behave, Zwiebel has refined new insect repellents that scream “Stay away!” far louder than any bug sprays currently on the market. Because they’re effective against a suite of pests, these repellents have the potential to save more then just picnics: They could also protect people across the world from malaria and other insect-borne diseases.

Popular repellents like DEET confuse bugs by blocking receptors and making it harder to find humans. These sprays aren’t foolproof because ants have a suite of sensory systems that bug spray can’t jam. “Ants have a plan A, plan B and plan C,” Zwiebel says. “They may not be as efficient with DEET, but they’ll still be able to get to you.”

Not only are products containing DEET not completely effective, they can also induce a slew of side effects in humans from rashes, dizziness and headaches, and there’s even evidence of more pronounced neurological damage in studies using rats. Despite the side effects, DEET is still one of the best lines of defense against not just ants but mosquitoes, which transmit deadly diseases like dengue fever, malaria, and sleeping sickness.   

Zwiebel and his team are working on a class of compounds they’ve discovered called excito-repellents that work by pushing the insect olfactory system into overdrive. He says that the excito-repellents he’s helped develop—many of which his team has applied to patent—work against all common pest insects, from moths to mosquitoes, and of course ants. “It’s like getting on an elevator with someone who’s put on way too much perfume,” he says. “You’d want to get away.” 

They’re in the process of scaling up this powerful repellent to develop a product that’s safe, economically feasible, and works as well against mosquitoes that carry malaria in Africa or Zika virus in South America as it does agricultural pests, as well as the nuisance insects that disrupt our picnics. The hope is that these excito-repellents can substitute for DEET and be used to create no-fly zones that would keep mosquitoes at bay. The repellents could also be incorporated into sheets and bedding that would repel bedbugs in hotels, into paint to deter yellow jackets from nesting, or beetles from infiltrating grain silos.

Their recent research indicates how and why the repellents are highly effective against bugs, but now they have to prove that there are no detrimental side effects for humans. “We believe we’re at that last hurdle now,” he says. No matter how good an insect repellent they’ve created, if it potentially harms humans then it’ll be off the table. The problem is raising the millions of dollars necessary to push it through toxicity testing.

“It’s exactly like a drug trial,” Zwiebel says, although at $150 million, the cost is substantially cheaper than testing a new pharmaceutical.

Zwiebel and his team are already funded under the Grand Challenges in Global Health Program, and they’ve applied for money from the Gates Foundation to pay for the toxicity trials to determine if they’re safe for human use. “We’re still not quite at the beginning of the end,” he says. “We’re at the end of the a critical moment where the [funders] are deciding whether or not to give us another dollop of money to go forward.”

These novel repellents have the potential to save lives across the world, but does he believe that the repellent will pass toxicity trials? “I would like to believe it’s non-toxic, but as a scientist I believe that the best way to answer those questions is to do the experiment. We’re ready to go to send it to product safety labs,” he says, “but we have to get someone to pay to get it done.”

“If we can bring these things forward and get them into the pipeline,” Zwiebel says. “Then we can improve the human condition.”

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