Mosquitoes, DEET and Evolution

There have been loads of references recently to the recent mosquito DEET story. Mosquitoes adapt to DEET rapidly and cease to be repelled by it. It has very wrongly been described as "evolution". It has nothing to do with evolution.... it is simple biochemistry/pharmacology.

Background

OK, DEET is a really effective mosquito repellent I first heard of it travelling to Florida. Some people seem to be inherently more pre-disposed to being bitten by mosquitoes than others... I am one of those people that seem to be extremely tasty! I guess it's because I smell nice? Anyway the Park Rangers showed me how to cover-up from the insects and slap on insect repellent This was remarkably effective. Having come from the UK, our products at the time (1970s) were woeful... but this American DEET containing product was really great. Don't confuse it with DDT which is a powerful insecticide... that builds up in insect eating animals etc. etc.

The Phenomenon

DEET is smelly. Insects don't like the smell. A phenomenon with smells is that you rapidly get used to them and cease to detect them. Take body odour (BO). The magic of BO is that you cannot smell it, and everyone else can? Noticed? It is because you have gotten used to the smell and can no longer detect it. Noticed someone walk in the room and say it smells like burning? The only way to check is to leave the room walk about and then walk back in and see if you can NOW smell it?

This is the phenomenon is known as desensitisation. Or technically "receptor desensitisation". It is also at the heart of many medical conditions in particular, physical drug addiction (psychological dependence is a bit different). So am I saying the DEET mosquito phenomenon is related to drug addiction? I certainly am. The science is the same.

The Science Bit

Here goes, hold on to your hats. Most drugs work by combining with a type of protein in the body called a receptor. Each drug has its own receptor. "Drug" in this context is a substance which causes a biological effect... it does not equate to "illegal substance" or "narcotic" or anything. Opium is a drug, but so is Sudafed (pseudoephedrine). Once the receptor protein has combined with the drug, it causes an effect or a "response". The response depends on the type of drug and receptor we are talking about. Some, like opium combining with opium receptors reduce pain and cause euphoria. Others cause blood vessels constrict or dilate... or make you sleep! Smells work in exactly the same way as drugs. (So do tastes.) They are chemical gases or vapours which dissolve in the snot of your nose and then combine with a protein receptor and cause a response. The response in this case though is simply to alert the brain to the fact that this particular smell is present.

So smells are just like drugs?

Well no, smells aren't like drugs, but the point is the the biological mechanisms by which they work are the same as the way drugs work!

With most drugs, there is a mechanism of receptor desensitisation where the same dose of drug causes progressively small effects each time you use it. The exact mechanism by which this happens is not entirely understood, but its investigated a lot of course!
So repeated exposure to a drug or a smell leads to that substance being detected less and less. With opium, to get the same kick... you have to take more and more. With smells this explains why you can't smell your own perfume (all day) or why you can rarely detect your own body odour!!! Mmm yum! What happens long term?
Well if you stop taking the drug, or you stop being smelly... you start to return to normal and become sensitive to the substance again! How long does it take? Depends on the substance. Can be minutes, can be days or weeks. For a human smell, its probably minutes. For it to, in ANY way, be like evolution it would have to pass on to the next generation!! The BBC should not just quote any unguarded comment that we scientists make, they should check it makes sense first.

The bottom line

So this seems to be all that is happening with DEET. The receptors desensitise. The "adaptation

" of mosquitoes to DEET is an interesting discovery, but not surprising in the light of our understanding of how smells work..... probably temporary and NOTHING to do with evolution!!!

Some translations:
opium is really a combination of natural opioids; mainly morphine.
The technical word for the process of smelling is "olfaction", the substance you smell is called an olfactant and the receptor it binds to is called olfactory receptor.

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What causes arthritis in people and animals/dogs

I am hoping to expand this section greatly, but for the time being lets keep this very simple:

In people there are two (common) very clearly distinguishable types of arthritis, rheumatoid arthritis and osteoarthiritis.  Hallmarks (according to a rheumatoid consultant colleague of mine) of rheumatoid are initial stiffness, whereas osteoarthritis tends to being with pain.  In dogs, arthritis is most commonly osteoarthritis, very similar to that seen in humans.  In all cases, there is some inflammation (so this includes swelling and stuff)... but rheumatoid is an autoimmune disease, where the body's own defence system attacks itself.

There are several treatments available, but the sad fact is none of them are terribly brilliant. Many will help a bit, prolong mobility and reduce pain, but there are no cures. 

Causes:  I think we would have to say rheumatoid is mostly genetic. Osteoarthritis is very clearly multifactorial.  There are several genetic factors which pre-disopose to osteoarthritis, but joint injury, excessive joint usage and obesity appear to be the cause in several cases.

What can you do about it?  The only thing we are reasonably confident of; is that keeping your own weight and the weight of your dog down.  Keep up regular exercise, but be aware that excessive force applied to joints could result in later development of osteoarthritis.

The Importance of Being Boring

Hmmm, I've just hit a problem with my grand entry into the blogosphere...   What I am hoping to do is bring some deeper explanation to some of the various science stories which hit the media (i.e., those I know something about!), and frequently to debunk the silly stories that emerge from a rather scientifically illiterate media.

...the problem: Well of course the media see there job as to make everything interesting!  No bad thing, except that accuracy is frequently abandoned and balance is not even on the radar!  So beware the science news source which has to sell its stories!  To be honest, scientists often have to exaggerate and skip facts to be understood... but the idea of this would be to retain the real essence of the story.  The media really just don’t care. Interesting/wacky/fun is the most important thing.  Nothing else really matters.  The Mail and the Express seem to be the worst, from reading the headlines on newspaper racks.  They seem to have a cure for osteoarthritis every month for example.  Has anyone ever thought... “how come they keep publishing stories about new cures, but I have it/ or my mum has it and there doesn’t seem to be a cure!?”.

Well on that particular one: there is no cure. Sorry.  May be one day, but it will come in so slowly (years of trials first) that it will probably bypass the newspapers all together.

So... If I set about taking interesting media science stories and debunking them, this is going to be an awfully tedious blog!!!

Dangers of #Phenylbutazone in your "Beef" burgers?

Now risk is a relative thing. There is never no risk. There is considerable risk if you walk to work/school. For the young road traffic accident is probably the greatest, for older people falling over is a definite risk! Particularly in the snow! However, try to avoid this risk and stay in bed all day and there is still risk. You would start to get bed sores and increase your probability of developing a thrombosis for starters!

So what's this got to do with #Phenylbutazone ("bute")? Well because no one can ever say there is no risk all we can do is class it between slight, low medium, high, and smoking. You know apparently several people each per year from tripping on aerosol cans?

So what is the risk from phenylbutazone from horse-meat?

Well a little background first. It was first used, really, for arthritis. It is called a "non-steroidal anti-inflammatory" ("NSAID") drug. It was used in much the same way as aspirin, ibuprofen and paracetamol (acetaminophen the USA). [Paracetamol is not technically classed as an NSAID for any smart arses but its pretty similar.] There are several other newer ones and probably safer ones too. Paracetamol and aspirin can both be deadly of course, but they are still classed as safe and of course available off the shelf. Aspirin is most famously dangerous because it causes bleeding in the guts and paracetamol is surprisingly toxic to the liver.

So phenylbutazone is old now, but it was introduced as an alternative to these NSAIDS. It worked reasonably well and it did NOT tend to cause people to suddenly drop dead. However, it had side effects of course, some unusual blood disorders and gastric bleeding (just like most NSAIDs). After thousands of people had taken phenylbutazone, it started to be clear that actually the side effects and interactions were relatively greater than with other NSAIDs so its use declined. Then between about 1970's to the 1990s a series of studies showed it could be carcinogenic... i.e., cause cancer. This pretty much killed its widespread human use, but it is still used commonly in animals including... horses.

So how carcinogenic was it? Studies were based on both humans and rat studies: 600mg per day for 10 days was shown to cause the first signs

of possible mutations taking place (first signs of cancer)... in rats it was established to occur at about 50mg per kg (i.e., equivalent to about 2.5 grams in a person). It clears the system in a day or so.

So how risky is it?

Well yes, if you gave a horse the standard dose (about 1 gram) and then killed the horse within the day and ate it you would consume some phenylbutazone. If you ate a whole horse and did so each day for 10 consecutive days... (if you did not die from overeating) there would be the possibility of some blood damage and potential gastric injury.

If you ate your own body weight in horse-meat, each day for 10 days you should be fine. If you ate your own weight in horse-meat everyday for several months, the phenylbutazone could reach the sort of mildly toxic levels people were worried about when it exited the human market.

If you ate a 1Kg 100% horse burger everyday, and it was fully dosed with phenylbutazone from the slaughtered horses you would only really consume about 5mg of phenylbutazone yourself. That is way way below the effective or toxic levels and it would clear quickly. So rephrasing: that is roughly 0.1mg per Kg which is therefore 1/500x the dose that gave problems for rats.

Does 1/500 sounds like too close for comfort?

Don't believe it: 500x the stated dose of aspirin, paracetamol or MOST drugs would be fatal to you. Please don't try it!

So how dangerous is phenylbutazone in beef burger contamination?

Not very.

...Disclaimer. This is my own personal opinion and it is sensible to accept whatever official governments advice emerges because this will include other safety factors. Also I expect that if the fraudsters who did this were prepared to swap horse-meat for beef they will have cut all sorts of other corners in terms of food hygiene and of particular concern to me.... animal welfare.