New type of insect repellant may be thousands of times stronger than DEET

May 9, 2011, Vanderbilt University

( -- Imagine an insect repellant that not only is thousands of times more effective than DEET – the active ingredient in most commercial mosquito repellants – but also works against all types of insects, including flies, moths and ants.

That possibility has been created by the discovery of a new class of insect repellant made in the laboratory of Vanderbilt Professor of Biological Sciences and Pharmacology Laurence Zwiebel and reported this week in the online Early Edition of the .

"It wasn't something we set out to find," said David Rinker, a graduate student who performed the study in collaboration with graduate student Gregory Pask and post-doctoral fellow Patrick Jones. "It was an anomaly that we noticed in our tests."

The tests were conducted as part of a major interdisciplinary research project to develop new ways to control the spread of malaria by disrupting a mosquito's sense of smell supported by the Grand Challenges in Global Health Initiative funded by the Foundation for the NIH through a grant from the Bill & Melinda Gates Foundation.

"It's too soon to determine whether this specific compound can act as the basis of a commercial product," Zwiebel cautioned. "But it is the first of its kind and, as such, can be used to develop other similar compounds that have characteristics appropriate for commercialization."

The discovery of this new class of repellant is based on insights that scientists have gained about the basic nature of the insect's sense of smell in the last few years. Although the mosquito's olfactory system is housed in its antennae, 10 years ago biologists thought that it worked in the same way at the molecular level as it does in mammals. A family of special proteins called odorant receptors, or ORs, sits on the surface of nerve cells in the nose of mammals and in the antennae of mosquitoes. When these receptors come into contact with smelly molecules, they trigger the nerves signaling the detection of specific odors.

In the last few years, however, scientists have been surprised to learn that the olfactory system of mosquitoes and other insects is fundamentally different. In the insect system, conventional ORs do not act autonomously. Instead, they form a complex with a unique co-receptor (called Orco) that is also required to detect odorant molecules. ORs are spread all over the antennae and each responds to a different odor. To function, however, each OR must be connected to an Orco.

"Think of an OR as a microphone that can detect a single frequency," Zwiebel said. "On her antenna the mosquito has dozens of types of these microphones, each tuned to a specific frequency. Orco acts as the switch in each microphone that tells the brain when there is a signal. When a mosquito smells an odor, the microphone tuned to that smell will turn "on" its Orco switch. The other microphones remain off. However, by stimulating Orco directly we can turn them all on at once. This would effectively overload the mosquito's sense of smell and shut down her ability to find blood."

Because the researchers couldn't predict what chemicals might modulate OR-Orco complexes, they decided to "throw the kitchen sink" at the problem. Through their affiliation with Vanderbilt's Institute of Chemical Biology, they gained access to Vanderbilt's high throughput screening facility, a technology intended for the drug discovery process, not for the screening of insect ORs.

Jones used genetic engineering techniques to insert mosquito odorant receptors into the human embryonic kidney cells used in the screening process. Rinker tested these cells against a commercial library of 118,000 small molecules normally used in drug development. They expected to find, and did find, a number of compounds that triggered a response in the conventional mosquito ORs they were screening, but they were surprised to find one compound that consistently triggered OR-Orco complexes, leading them to conclude that they had discovered the first molecule that directly stimulates the Orco co-receptor. They have named the compound VUAA1.

Although it is not an odorant molecule, the researchers determined that VUAA1 activates insect OR-Orco complexes in a manner similar to a typical odorant molecule. Jones also verified that mosquitoes respond to exposure to VUAA1, a crucial step in demonstrating that VUAA1 can affect a mosquito's behavior.

"If a compound like VUAA1 can activate every mosquito OR at once, then it could overwhelm the insect's sense of smell, creating a repellant effect akin to stepping onto an elevator with someone wearing too much perfume, except this would be far worse for the mosquito," Jones said.

The researchers have just begun behavioral studies with the compound. In preliminary tests with mosquitoes, they have found that VUAA1 is thousands of times more effective than .

They have also established that the compound stimulates the OR-Orco complexes of flies, moths and ants. As a result, "VUAA1 opens the door for the development of an entirely new class of agents, which could be used not only to disrupt disease vectors, but also the nuisance insects in your backyard or the agricultural pests in your crops," Jones said.

Many questions must be answered before VUAA1 can be considered for commercial applications. Zwiebel's team is currently working with researchers in Vanderbilt's Drug Discovery Program to pare away the parts of VUAA1 that don't contribute to its activity. Once that is done, they will begin testing its toxicity.

Vanderbilt University has filed for a patent on this class of compounds and is talking with potential corporate licensees interested in incorporating them into commercial products, with special focus on development of products to reduce the spread of malaria in the developing world.

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1 / 5 (2) May 09, 2011
Hope it doesn't trigger similar response to humans :)
3.7 / 5 (3) May 09, 2011
This sounds sadly like a very good way to troll bees...
2 / 5 (4) May 09, 2011
I'm sure this won't end well.
1 / 5 (1) May 09, 2011
I'm good with anything with DEET's effectiveness that doesn't taste nasty, melt plastic, or sting my lips.
1.3 / 5 (16) May 09, 2011
An unborn child died to make this possible. What happened to LIFE liberty and the pursuit of happiness.
1 / 5 (1) May 09, 2011
Let's just hope it doesn't turn out to be carcinogenic . . .
1 / 5 (1) May 10, 2011
Carcinogenic hummmphh No worse then DEET.
3.3 / 5 (7) May 10, 2011
An unborn child died to make this possible. What happened to LIFE liberty and the pursuit of happiness.

Nothing has happened, why do you ask? Are you feeling like your rights to this are under threat of being taken away?
2.3 / 5 (3) May 10, 2011
I can just see it now. The compound inadvertently and permanently messes up all humans sense of smell. Afterwards, feces and burnt food smells like flowers.
3.3 / 5 (7) May 10, 2011
An unborn child died to make this possible. What happened to LIFE liberty and the pursuit of happiness.

The same thing that happened to life, liberty and pursuit of happiness of crops growing out there on the field. Only life with sufficiently developed brain possess these rights. Embryos do not qualify.
2 / 5 (2) May 10, 2011
panpsychism or BUST
3 / 5 (2) May 10, 2011
Insects will just evolve and find a workaround to the disrupted sensors.
not rated yet May 10, 2011
That's true if their receptors act the same as ours, in that they will desensitize as they are exposed to the chemicals. Although, it may not be an issue if the mosquito follows its basic programming and flies away from the stimulus... in which case it will not get that desensitized.
not rated yet May 11, 2011
I wasn't referring to a change of genetic code, or adaptation on that scale. I was only referring to the temporary numbing of a sense to certain stimuli when under constant exposure to it, like when entering a room with a bad smell, and the smell eventually fades from our notice, until we leave the room for a bit and return.
not rated yet May 12, 2011
It directly stimulates a specific cell type, this isnt the same as developing a resistance to a toxin. Overcoming this from an evolutionary perspective could mean distrupting their sensory structure, which makes it difficult for an evolutionary work around.
Also, this sounds like it could be temporary, like a venom, but i don't think the article mentioned lasting affects. I'm curious to find out. If the compound does end up being non reactive, sounds more like the definition of an actual 'repelent' to me than the 'insecticides' we use today. Which would be ideal.
1 / 5 (1) May 16, 2011
An unborn child died to make this possible. What happened to LIFE liberty and the pursuit of happiness.

What happened to your ability to think? When President Bush approved using (about sixty) existing stem cell lines in Federally sponsored research, it was because the research needed to be done to find out how embryonic stem cells were different from adult stem cells. Idiots screamed that this prevented development of life-saving treatments using embryonic stem cells, ignoring the fact that the marker for cell lines to be classified as embryonic are the cancers they cause when grown in a host.

The research was done, and it is now possible to flip adult stem cells to embryonic and back again. Adult stem cells are safe for use in therapy, and in fact are used dozens of times every day for just that. (Mostly bone marrow transplants.)

So now, when a researcher refers to stem cells as embryonic they are referring to teratogenic activity, not to the source.
1 / 5 (2) May 16, 2011
Perhaps the researchers need to do a little more research on insects and mosquitoes basic biology. Insects like humans have several senses that they rely on to find food - and smell is just one. While a loss of effective olfactory usage might be confusing, it certainly doesn't limit most organisms ability to eventually finding food.
not rated yet May 17, 2011
Yes, and Mr. Kantknowall needs to read this article about how they use vitamin C to convert skin cells to stem cells:
not rated yet May 17, 2011
Some of us don't care about particulars, but we DO care about 'bug dope' that works. Those of us who buy coils and sprays by the cases!! So if it really works - perfect it and get it to Fairbanks, AK QUICK!!! =)

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