Ultimate bug repellant may help fight malaria and other insect borne diseases

From Vanderbilt University, scientific serendipity swats smell:

New insect repellant may be thousands of times stronger than DEET

Colored scanning electron micrograph image of an Anopheles mosquito that spreads malaria. (Copyright © 2011 Photo Researchers, Inc. All Rights Reserved.)

Colored scanning electron micrograph image of an Anopheles mosquito that spreads malaria. (Copyright © 2011 Photo Researchers, Inc. All Rights Reserved.)

by David Salisbury

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 Proceedings of the National Academy of Sciences.

In preliminary tests with mosquitoes, the researchers found the new class of repellant,  called Vanderbilt University Allosteric Agonist or VUAA1, to be thousands of times more effective than DEET. The compound works by affecting insects’ sense of smell through a newly discovered molecular channel.

“If a compound like VUAA1 can activate every mosquito odorant receptor 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,” said Patrick Jones, a post-doctoral fellow who conducted the study with graduate students David Rinker and Gregory Pask.

The researchers have just begun behavioral studies with the compound.

“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 was made during tests that are 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.

Graduate student David Rinker. (Susan Urmy, Vanderbilt University)Graduate student David Rinker. (Susan Urmy / Vanderbilt)

“It wasn’t something we set out to find,” Rinker said. “It was an anomaly that we noticed in our tests.”

A different sense of smell

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. Odorant receptors, or ORs, sit 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.

Professor Laurence Zwiebel talking with a student in the lab. (Neil Brake, Vanderbilt University)
Professor Laurence Zwiebel talking with a student in the lab. (Neil Brake / Vanderbilt)

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,” he continued.  “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.”

The process of discovery

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.

Post-doctoral fellow Patrick Jones. (Susan Urmy, Vanderbilt University)
Post-doctoral fellow Patrick Jones. (Susan Urmy / Vanderbilt)

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.

Graduate student Gregory Pask. (Susan Urmy, Vanderbilt University)
Graduate student Gregory Pask. (Susan Urmy / Vanderbilt)

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.

“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.” Patrick Jones, said.

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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h/t to WUWT reader Scott Ramsdell

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50 thoughts on “Ultimate bug repellant may help fight malaria and other insect borne diseases

  1. thousands of times

    Good. The last time this sort of thing made the news it was only 10X.

    http://www.ag.iastate.edu/aginfo/news/2001releases/catnip.html
    CATNIP DRIVES CATS WILD, BUT DRIVES MOSQUITOES AWAY

    AMES, Iowa — Although it drives cats wild, catnip appears to be a big turn-off for mosquitoes.

    In research conducted at Iowa State University, catnip was 10 times more effective at repelling mosquitoes than the compound used in most commercial bug repellents. (more)

  2. Now you know I just can’t help but wonder what you’re thinking out there….can we isolate the IPCC Orco?

  3. In the spirit of Rachel Carson, they will be all over this like stink on hooey. Can’t have anything effective enter the market place, it might save lives.

  4. Fund the grant. Do the research.
    This sounds like it has great potential.
    So far, I see good science productivly at work.
    We need to encourage this.

  5. Does it just repel or eventually destroy the mosquito as well? If it were to wipe out mosquitoes, there are more than a dozen higher vertebrates that would be negatively impacted and, perhaps, even sent to extinction.

  6. 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,”

    Interesting though it is,
    What about the non-nuisance insects, e.g. the pollinators, how can VUAA1 be restricted in distribution, how long does it last, what compound does it break down into ?

  7. They finally released the bin Laden photograph!

    No. But quite a photo. Not exactly a poster child. Yet in our ‘enlightened’ times I would half expect some endangered ‘species’ of mosquito could be threatened by this. If not I am sure they could discover one.

    With all this water coming this year there could be a real bumper mosquito crop around here and I’m not looking forward to that. I’ll just have to disrupt their antennae one set at a time.

    Or wait. Will Climate [insert latest term here] cause mosquito extinction too?

  8. Keith Minto
    What about the non-nuisance insects, e.g. the pollinators,

    My thoughts also, we are losing more of our pollinating insects, especially bees with brood fever and varroa mite. Will this disrupt the sensors they need as well?

  9. will do nothing to eliminate those diseases … may prevent some people from being infected …

    Try DDT, solves the problem permanently …

  10. I foresee environmental lawsuits to stop this one in its tracks. It would be unnatural to effectively shut mosquitoes off from feasting on the human race. If a Mr. Desert Tortoise has rights, so does Mr. Mosquito. Malaria threatened humans fall somewhere down the line on the environmental priority tree.

  11. If my hair doesn’t fall out too I’m a big fan. My wife is content to watch, for now. This is a big improvement over what we used to use in Hawaii when I was a kid – guppies! All the fresh water ponds had guppies and other Poeciliidae in them.

  12. Isn’t this the kind of thing we pay scientists to discover? Even if it doesn’t work commercially (yet) and the press release has a butt load of disclaimers and field tests are a long ways off and it may have unintended consequences and is patent encumbered (grump), it’s still a fine bit of real science. Real scientists do exist!

  13. The Greens will hate this.

    After all, malaria is primarily a disease of the poor.

    Developed countries don’t have a big malaria problem.

    And most Greens are spoiled rich kids.

  14. They have named the compound VUAA1.

    At least the University of Florida had the good sense to name their lab-developed new stuff something marketable – like Gatorade.

    VUAA1? What kind of advertising campaign can you begin with that? 8<)

    By the way, if the skeetters trace humans by their exhaled CO2, you'd think somebody would link "decreased mosquito sensitivity" as a CAGW impact.

  15. Ths compound must be banned immediately.

    It will infringe upon insects rights to a normal life under the European Convention on Human Rights.

    And it will probably contribute to global warming!

  16. Sorry, but we cannot let this research continue. We will not be able to catch enough bugs to eat when they ban us from eating meat because of methane emissions. :sarc off

  17. P.F. says:
    May 10, 2011 at 10:16 pm
    Does it just repel or eventually destroy the mosquito as well? If it were to wipe out mosquitoes, there are more than a dozen higher vertebrates that would be negatively impacted and, perhaps, even sent to extinction.

    If if the exposure to VUAA1 permanently affects mosquitoes, then I suppose it would eventually wipe them out. OTOH, if using the compound makes humans sterile, then I suppose it would eventually wipe us out.

    Too many “ifs”right now. We’ll have to wait and see.

  18. Robt is confused about catnipping mosquitoes.

    If catnip drives cats wild, and wild cats are, well, in the wild and are, well, uhm, already behaving wildly (your generic puma/mountain lion/panther/jaguar, wildcat, and bobcat for example are not on the average well domesticated) …. then if Robt liberally smears his bod with catnip before walking through the brush …..

    is he repelling cats or attracting cats or driving those previously mad cats he repelled even madder?

  19. This discovery illustrates why you should not be afraid of claims of global warming leading to an increase in the rate of malaria or its spread. It’s called human ingenuity. Think also shale gas.

    Here are a few links on how mosquitoes manage to find humans – partly on your exhaled CO2!!! I knew it had to be a culprit. ;O)
    http://onlinelibrary.wiley.com/doi/10.1002/9780470514948.ch7/summary
    http://www.control-mosquitoes.com/#mf11
    http://tinyurl.com/yj9yzzb

  20. Keith Minto says:
    May 10, 2011 at 10:36 pm

    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,”

    Interesting though it is,
    What about the non-nuisance insects, e.g. the pollinators, how can VUAA1 be restricted in distribution, how long does it last, what compound does it break down into ?

    This is an excellent point. The problem with mosquitoes for me is at night time. Perhaps application could be restricted to the inside of a house only. I would hate to deter pollinators in our fruit and flower rich garden. ;o)

  21. While there may be open questions about the use and effectiveness of this new repellent, I have to say that THIS is the kind of thing I want our government research dollars to be funding – not some nonsense CAGW “study” about a “potential” 25 m sea level rise in the year 2100…

  22. You Just know the envirowackos will find some basis on which to ban this stuff–mosquito extinction or something…

  23. 1000 times more effective than DEET. Well, in my experience DEET doesn’t work at all, so that would make it 1000 times more effective than nothing.

  24. “By the way, if the skeetters trace humans by their exhaled CO2, you’d think somebody would link “decreased mosquito sensitivity” as a CAGW impact.”

    I actually did some very interesting research on this.
    I’ve tried to upload it several times, but my wifi seems to be all flummoxed…
    /sarc

  25. The other question is how much does it cost? There are other things besides DDT that kill mosquitoes, but they cost too much for most African countries to use.

  26. Great news. Found while fishing for salmon that cigars will also keep mosquitoes away. Unfortunately, they also keep my Lovely Lady away so I have to choose wisely. This will remove yet another excuse for continuing to partake – and I will still have to choose wisely. Cheers –

  27. It sounds like it would gag a maggot and not bother people. Something like that could wipe out or control fire ants since they rely on odor trails. There is all sorts of potential for something like that but it sounds like there would be an equal potential for abuse.

  28. I could see a problem with crop use if you want bees or other pollenators to come to your crops. It doesn’t seem to discriminate between good and bad insects

  29. A lot of potential problems will depend on how it’s to be applied. If it’s impregnated in cloths or screens or bedhangings, etc., or sprayed on to humans, it shouldn’t have an impact on pollenation. BTW, let’s not limit it’s use to Africa; here in Florida we could use an effective mosquito repellant. As Reynolds says: “Faster please.”

  30. Don’t think this one will last long. Most of our crops are pollinated by bees. If it is short-lasting, though, it has real possibilities.

    In urban areas, it will be very popular, but it will destroy most urban gardens

  31. The comments here remind me about my fear about an effective insect poison I found last year. It actually kills bugs and my house was bug free all winter. They weren’t able to survive within the walls.

    I am terribly afraid that the EPA will find out that this bug poison is, well, ……poison.

  32. “Jones used genetic engineering techniques to insert mosquito odorant receptors into the human embryonic kidney cells…”

    Does this mean that the cells were taken from an aborted child? If they were then… what? That’s okay? We can do that. It’s fine to use parts of dead children to develop new products?

    Or am I missing something in the description? Could someone enlighten me here please. I’m feeling sick.

  33. Can I get it in liquid form, and paint my golf bag with it?

    Or – better yet – my inlaws have a back veranda that they never use because of the mosquito plague in their part of the world. Just spray some of this around, and fire up the barbecue.

  34. insects are one of the bases of all ecosystems
    the whole lifecycle of insects is pheromon controled
    literaly destroying the sense of smell for insects in general, all of them without selection, has the potential for catastroph, only compareabe to termonuclear war.
    they need to be really carefull and tripple think about what they are doing.

    sorry for my bad english

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