Biology
concepts – thermosensing, repellent, odor receptors, gustatory receptors,
semiochemcials
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Science
explains our world, and then technology and engineering
build
a model of that for our use. The better we know how our
universe
works, the better we can make use of it. In the 1985
film
Real Genius, this difference is
stated when the scientist
students
ask what a 6 megawatt laser might be for, one student
says,
“Let the engineers figure out a use for it.” In this case, they
used
it to fill a house with popcorn.
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As an example –
we know that certain naturally occurring oils and well as some man made
chemicals keep mosquitoes from feeding on us. This is the observation. But the question is – how do mosquito repellents work? The
answer is more interesting and more complicated than you would initially think.
Repellents rarely repel.
Investigating how
chemicals keep us from getting bitten will teach us about how the living systems
work, will give us a better understanding of our universe, and then give us better
insect repellents. Don’t think that’s important? Consider the hundreds of
millions of people who are infected every year (several million die) with
mosquito-borne diseases (malaria, encephalitis, dengue fever, yellow fever,
filiariasis). So yes, we need more repellents.
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Mosquito
borne diseases can be unpleasant at best. Top left is
filariasis,
a worm is transmitted via mosquito and it clogs up
your
lymphatic vessels, so that body parts swell from excess
fluid.
Top right – malaria can result in so much red blood cell
lysis
that your spleen (the guy who cleans them up) can
rupture.
Bottom left – Dengue fever is often called breakbone
fever,
the pain is not something an image can express. But the
hemorrhagic
form of the disease can produce some bleeding
in
weird places. Oh, and it can kill you too. Bottom right –
yellow
fever is caused by a virus transmitted by mosquito. Your
liver
breaks down and causes your whole body to turn yellow
and you
bleed into your skin.
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We should start
with the repellents for which we have good ideas of their mechanism of action.
But there aren’t any. We have some hypotheses and working ideas of the modes of
action of mosquito repellents, but nothing is definitive yet. Let’s look at two
of them and see if we can find some common pathways.
Citronella oil
Citronella is a
combination of many different natural oils produced in lemongrass plants (Cymbopogon nardus and Cymbopogon winteratu). As a natural oil and a flavoring in Asian
cooking, one would think that citronella oil would be considered just about the
safest insect repellent this side of a slap with an open palm.
The EU, on the
other hand, said that the repelling function of citronella oil hadn’t been
proven and it was deemed illegal to use in the EU in 2006. Oh, you could eat
it, and use it soap or perfumes, you just couldn’t use it to keep mosquitoes
away. They reconsidered in 2014 and some restricted uses of citronella oil as a
repellent are now allowed.
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Citronella
oil comes from the lemongrass plant (Cymbopogon
nardus or Cymbopogon winteratu). There are two major species
for
acquiring the oil, and the oil from each is a little different in
the
percentage of each chemical. Lemon grass is also used in
cooking,
the woody stalks are used with extra long cook times.
The
torches that burn citronella oil work pretty well, but you
have
to stay in the volatilized cloud of oil for them to be efficient.
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Citronella oil probably
works in a couple of ways. It's strong and sweet smelling, so it covers up and
dilutes the odors that mosquitoes use to find you. If they’re detecting all the
citronella in the air, then they aren’t smelling you. But research also shows
that citronella oil activates TRPA1 ion channels. In us, they detect cold and
noxious chemicals and are interpreted as pain. It is very possible that the
detected signals in mosquitoes just come through as something unpleasant and to
be avoided.
In this way,
citronella would be an actual repellent. It repels on contact as well, as the
taste is thought to activate bitter taste receptors and contact greatly reduces
feeding time.
But citronella
only seems to work when you are in the cloud produced by burning the candles or
torches, or within the area of the spray. And if you’re using an oil or cream
with citronella, it should really be reapplied every 30-45 minutes - not the
most user-friendly method for discouraging pests.
DEET
World War II in
the Pacific was an insect nightmare for the US Army. In response to the
plethora of insect-borne disease that ran through the allied forces, defense
scientists starting looking for better insect repellents. In 1946, their
efforts produced N,N-Diethyl-meta-toluamide, or DEET.
Just how they came up with DEET is a mystery to me, it must
have been a massive exercise in trial and error. Why? Because we know less
about how DEET works than we do about citronella oil. And that’s with the benefit of 40 years of
research. They didn’t have a clue how it worked or even what systems it was
targeting when developed in the 40’s.
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Guess
which hand has been treated with DEET. The
mosquitoes
come very close to the hand that was treated,
but
don’t land on it. This argues that DEET is less repelling,
than
it is disguising. On the right, the structure of DEET is
similar
to several human semiochemicals, it fits into the lock
and
key system of several odor receptors and activates or
inhibits
them.
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More recent studies have been more rigorous, but haven’t
helped solve the puzzle. A 2008 study suggested that DEET was actually repellent;
the mosquitoes didn’t like the smell and would avoid it. But other studies have
shown different mechanisms of action.
A study in the journal Nature in 2011 found that mosquito
odor receptors could be confused by DEET. The receptors for octenol were less
responsive in the presence of DEET, but other receptors more more
responsive. The conclusion of the
study was that odorants from humans could be detected, but their pattern was
confused, so the mosquito didn’t recognize the target as a target. It’s as if
we disappear from the mosquitoes radar when we wear DEET.
A 2010 study showed similar results. DEET activated certain
odor receptors but not others when given alone, but the opposite effects were
seen when DEET was given in the presence of things from human sweat that would
normally attract a mosquito. Once again, the signals were confused. This is
really more of a chemical disguise for us, not a repellent. Next time your kids
go outside, you should insist that they apply their mosquito confusant.
However, a 2013 study in the Journal of Vector Ecology found
that heat and moisture were critical elements for recognition of targets by
female mosquitoes, and that DEET messed not with odor, but with detection of
heat and/or moisture. Different from the other studies, but still more of a
masking than a repellent.
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Something
a little disturbing. Mosquitoes can learn to ignore
DEET.
Most mosquitoes will be confused by DEET and never
find
you. But if they do and then are repelled by the taste, they
learn
from that and the second taste is not repellent. Hopefully
they
just don’t find you a second time.
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Weird - Orco is needed for both DEET to work and for mosquitoes
to find humans more attractive. I haven’t figured that one out yet. The
researchers showed that DEET only maintained an effect on the Orco mutant
mosquitoes when they landed on a DEET covered surface, and then they didn’t
like it at all.
This suggested that DEET might have more than one mechanism,
confusion in the air and repellent taste on contact. Older studies supported
this idea, as a couple of studies in 2005 and 2006 showed that contact with
DEET would reduce feeding behavior in mosquitoes and one in 2010 showed that
fruit fly bitter taste receptors are activated by DEET.
So, we have studies that say DEET is a confusant rather than
a repellent, others that say it is a true obnoxious smell that they can’t
stand, and yet others that say DEET is confusing to the smell and repellent to
the taste. But there are more. Other studies suggest that DEET actually
inhibits the smelling of anything, while others say that it inhibits an
important protein called cytochrome p450.
Used
commercially since the 1950’s, DEET has been the gold standard for efficiency
for many years. Although it has to be used at fairly high concentrations, it
can keep mosquitoes away for 4-6 hours at concentrations where citronella oil
might work for less than an hour. At 100% concentration, DEET is active for
more than 12 hours. What’s more, if you combine DEET with 5% vanillin, it works
two hours longer!
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A
lime with cloves stuck in it as a mosquito repellent – really?
Well,
lime is kind of like citronella oil, and clove has eugenol,
which
acts on TRPV1 ion channels. But how many would you
have
to have, or do you wear them like earrings? Penny royal
contains
menthol and mosquitoes stay away from it. But it
also
has toxins that will kill you.
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On the other
hand, DEET dissolves plastic, foam rubber, spandex, gore-tex, and nylon. I can
see where this might make people leery about slathering it on their skin for
hours at a time. And a few people are allergic to DEET, so the best current repellent
isn’t without some negatives.
One last point
– a newer repellent called picaridin
is almost as effective as DEET and doesn’t eat your back packing equipment and
clothes. The interesting point is that picaridin is a synthetic version of piperine, the spicy chemical in black
peppercorns. Add to this that menthol is also a fairly decent mosquito repellent,
and we have some good arguments that TRP receptors might be involved in
repelling activity – as with citronella oil. Piperine is a TRPV1 agonist, and menthol
activates TRPM8 and TRPV1. All our talk about spicy food and heat/cold receptors
has an impact even in the spread of malaria and other deadly diseases!
Next week,
another question to answer - do sunflowers really turn with the sun?
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