Getting to the Heart of the Health Effects of Pollution

Researchers at the University of Rochester, US, have taken an elderly groups of rats on the rodent equivalent of senior citizens road trip to find out how air pollution breathed in by motorists might be harmful to health. Alison Elder and her team wanted to understand why heart attacks seem to occur more often on days when the air quality is bad. They took a collection of aged rats with high-blood pressure on a six hour, 320-mile drive west of New York. Throughout the journey and for five days afterwards the rats, which breathed the same air as any road-user would along the route, had their heart rates, electrocardiograms and blood pressures measured regularly. The study revealed that the well-travelled rats showed a 10% drop in heartrate and a 70% decrease in the responsiveness of their autonomic nervous systems, the neural network that controls subconscious processes like breathing, blood pressure and heart rate. "The fact that exposure to air pollution can change the heart rate, independent of other factors, is a cause for concern," Elder said. "It's important to understand that these changes are taking place outside of the lung. Air pollution is either having a direct effect on the heart in rats or is altering something within the circulatory system." Scientists suspect that the culprit could be ultrafine "nanoparticles" pumped out by engines. They're 60,000 times more numerous than the larger, coarser particles such as PM10s and PM2.5s, which are routinely measured as an index of air pollution. These tiny particles are likely to be able to penetrate deeply into the lungs and enter the circulation. By interacting with blood platelets, which control blood clotting, the particles could increase blood stickiness, making it more likely to form an artery-blocking clot.

4th Feb 2007

How colour can help in the mating game?

Chris - Now for the final part in our science of colour series, Naked Scientist Anna Lacey has been looking at how animal coloration can be helpful in finding a mate, and how some colours that animals use are completely invisible to the human eye. But to kick us off, Anna's going to try a little experiment, guess where? In her favourite place, the pub.

Anna - I've come down to my local pub to see if I can woo some unsuspecting males with the colour of my clothes. So excuse me there gentlemen, there's a nice table of three gentlemen here, what do you think of my maroon stripy t-shirt and my blue jeans?

Man 1 - Very attractive actually. I'm really liking the stripes on your top.

Anna - Well thanks very much, that's very kind. And what about you?

- I would say something very similar. I think the maroon suggests a very bright colour and a very vibrant colour. Suggests a lot of fun.

Anna - So now to the third gentleman here. What would you think about me based on the colour of my clothing for potential mating opportunities and perhaps being a partner, whatever?

Man 3 - Well my girlfriend would kill me for saying this but I very much like the maroon, but that the denim's a little bit standard.

Anna - Ok, well that actually turned out quite well for me. Thanks for that guys. But it turns out that a whole range of animals, and birds in particular, actually use their own version of clothes or brightly-coloured feathers to try and bag a mate. So to find out why these colours are so important, I went to the botanic gardens to speak to Cambridge University zoologist Nicola Nadeau.

Nicola - Why females would be particularly attracted to these colours is an area of debate at the moment. But it's thought they could indicate the fitness of the bird. So if these colours are particularly costly to produce, then that could indicate to the female that I'm a particularly strong and healthy male.

Anna - Isn't it also the case that the colours that we see in birds aren't necessarily what the birds are seeing?

Nicola - Yes, so we've only got three types of photoreceptor in our eyes and these can detect green and red and blue. Whereas birds have a fourth, and this can detect ultraviolet light, which we can't see. So for example blue tits, they look the same to us but the males have these ultraviolet ornaments that we can't see.

Anna - So are they using that again to try and attract the females?

Nicola - Yes, so it's thought that healthier males have brighter UV ornaments and the females can detect these and use them in mate choice.

Anna - Lots of animals use UV ornaments and patches to attract mates, but how on earth do you go about making the colour UV in the first place? Well it turns out that you can actually do it in two different ways. Now one of these is with pigments, so something equivalent to a paint, and the other is by something called structural colour, and for that to work you need to use a process called interference. Now this works by having tiny barbs or scales that act a little bit like reflectors, and these are spaced at specific distances so they reflect certain wavelengths or colours of light, and cancel out all the others. Mike Majerus, a Professor of Evolution, explains a little bit more about this and how it works in butterflies.

Mike - Butterflies are in the insect order Lepidoptera, which simply means 'the scale wings'. The wings, if you've ever touched a butterfly with your fingers, you get all these scales just rubbing off and they're literally covered with thousands of these tiny scales. That gives them this enormous capacity for fabulous colour patterns.

Anna - So how does the colour actually form through the structure of those scales?

Mike - The scales, they're like tiles on a roof. They're placed very close together at an angle, and at the top end, you'll get a tiny gap. Now the distance between it causes an interference effect as white light hits it, and just by putting the scales at greater or lesser distances, you can get different physical reflectances.

Anna - So what kind of colours can you get with this structure with the scales? What's the potential for that?

Mike - Oh for the reflectance patterns, they can be virtually any colour, but the most common are blues and greens. Once you go into the chemical pigments, you can get any colour you like; all the colours of the rainbow.

Anna - But for birds like blue tits, some pigments are actually quite rare. Here's Nicola again.

Nicola - Well in general, there aren't any blue pigments that are used in birds so all blues will be structural.

Anna - So the garden blue tit, it's not actually got any blue dyes if you like in its feathers. It's all to do with the structure of its feathers reflecting light in a certain kind of way.

Nicola - Yes exactly. So if you took the feathers and mushed them up, they wouldn't appear blue. It's just purely the structure of the feathers that's producing that colour.

Anna - So it turns out that colour's not just about slapping on a bit of paint. Because of all the different colours out there, some are made by pigments, some are made by tiny structures in the wings and feathers of the animals, and some colours just need a bit of both. And what's even more amazing is that there's a whole load of these colours that we can't even see. But what we have seen over the past few weeks is that colour spans a whole range of disciplines from biological greens to chemical purples, and also how it's completely revolutionised the world of fashion, medicine and got far enough under our skin to change our behaviour. So by just looking at the word 'colour', what we've actually done is taken a journey through physics, biology, chemistry and psychology. Meaning that we've not only learnt about the science of colour, but a little bit about the diversity and colour of science.

February 2007

People who don't Feel Pain

Chris - Geoff recently published a paper on people who seem to congenitally, in other words have a genetic preponderance, not to be able to feel pain. So tell us about these people.

Geoff - We came across a bunch of children who were reported never to have felt pain. At first we didn't believe that this was the case, but we slowly saw a number of these children and they and their parents reported that they'd never felt pain of any type throughout their lives; whether they'd fractured bones, burnt their skin, scalded themselves drinking boiling water. It was a huge problem for the parents bringing these children up and later on for these people for when they became older children, teenagers and later adults. Furthermore, there was nothing that we could find wrong with their nervous system. They had normal intelligence, they had normal nerves, the nerves seemed to conduct signals normally, their brain seemed to be put together normally, and it didn't make any sense by the current theories of how pain is controlled. So we set about trying to find if there was a genetic disease that they had, because it wasn't all people in the family that were affected by this condition; it was just some members. So we used three families where the parents were first cousins, so-called consanguineous relationships. Using those three families we mapped the condition down to a gene called SCN9A, and in each of our three families we found a different fault in that gene that abolished its normal function.

Chris - Where is that gene turned on? What cells carry that gene and switch it on?

Geoff - It's not entirely clear at the moment. It's probably expressed in a number of parts of the brain and in a number of different types of nerves, but it's very highly expressed in the pain sensing nerves. It probably has a redundant function elsewhere, but in the pain sensing nerves it seems to be expressed only at the very tips of those nerves and it's at the tips that pain is sensed.

Chris - So what does it do? How does it work?

Geoff - All pain is tissue damage, so it's very important that a species knows it's being damaged and can stop itself from being damaged. It seems there are a whole series of proteins that detect various types of damage, be it hot, cold, pressure, etc. These seem to be integrated together by this SCN9A, which seems to be an amplifier that takes these small initial tissue damage signals and turns them into a much larger sodium impulse and a nerve can fire. The brain can then sense that there's tissue damage going on and avoid it.

Chris - So it's almost like an engine. You turn the key but the engine doesn't start, and what you've got in your nerves is lots of starter motor activity but there's no firing of the engine.

Geoff - Absolutely right.

Chris - So why should these families have this? What's happened? Where did this change come from?

Geoff - I guess it's just the random mutation that happens in the human genome. Unfortunately if the mutation happens in an essential gene, it's going to give rise to damage.

Chris - Why is it so uncommon?

Geoff - I don't know. Some diseases are desperately rare and some are common. We usually use the excuse that if the disease is common, there must be some benefit to carrying that disease, but it's very unclear. Probably this gene's very important and any mutation in it is not well tolerated and is usually got rid of as time goes by.

Chris - Now you mentioned that the people who you spotted that had this problem couldn't feel any pain. They had inbred within their families so that means one person was carrying one dodgy copy of the gene and they got together with someone with another dodgy copy. When you put the two together, you end up with two dodgy copies of the gene, which is why they can't feel pain.

Geoff - Yes, that's absolutely right. We all have two copies of most genes. Just having one faulty copy is fine because as long as you've got one good copy of the gene telling the body what to do, everything seems alright. The parents of these children have no problems at all with their pain sensation.

Chris - But what I'd like to ask Geoff is that if you normally have two copies of this gene and they're working and switched on, does this mean that if I married someone who has one copy working and had children with them, that you'll get kids that only have one copy of the gene working and therefore they'd be less sensitive to pain than I would be?

Geoff - No that doesn't seem to be the case. Most diseases like this are called recessives and carriers of recessives are very common in the general population. Carriers have no minor features of the disease they carry; they're just normal. So we don't think it matters if you carry a fault in this gene. We have extended our studies as we discussed prior to this programme, looking at changes in the gene that occur called SNIPs - variants that go in almost all genes.

Chris - So that's just natural variation people have in the population. It doesn't switch the gene off, it just means it maybe works slightly differently from one person to the next.

Geoff - Well we've asked that very question. Is there any link between the degree of pain people feel and changes in this gene which occur in the normal population. And it seems that this gene is one of about three or four genes where small changes in its function change our pain thresholds.

Chris - So if you've got a gene that only seems to make a difference to your nervous system when it's in a pain-conveying nerve fibre, does this gene explain why some people for instance have an incredibly high pain threshold, while other people seem to wince at a gnat flying past them?

Geoff - I think it does and it could be one of the explanations. There's a number of genes now that have been found to alter people's susceptibility to pain. Initially people were thought to lack moral fibre et cetera, but it seems that there's a strong genetic basis to feeling pain differently. It's always been the case that some children cry when blood's been taken and people say that they're not being brave. Some women need a lot of pain control when they're having babies while others need very little. It now actually seems that these people have different abilities to tolerate pain.

Chris - What were the consequences for the people in Pakistan in the families you studied?

Geoff - Much greater than being rather stoic.

Chris - Because it seems rather exciting because when I go running, it's actually the pain of being grossly unfit that holds me back. Could these people become super athletes for example because they can't feel that they've got this heart-wrenching stitch and their legs are about to collapse and feel as though they're gasping for oxygen?

Geoff - We thought along the same lines as you, that pain was holding us back from being able to do better things. But in fact no, pain is actually there for a very very good purpose. Pain is telling you that you're working too hard and starting to cause tissue damage, and if you carry on you'll either break bones, tear muscles or fall down exhausted. These children and some adults we've now met with this condition have none of those restraints on their body and so they continually damage themselves.

Chris - They do dangerous things.

Geoff - Not necessarily. They don't deliberately do dangerous things. When they're children they'll do stupid things because they don't know to stop running into walls and jumping off high areas.

Chris - One of them jumped off a roof and died, didn't he?

Geoff - Yes that's right and he did that on his birthday because he'd had none of the restraints the rest of us have to stop us doing dangerous things. He was just trying to give his friends a great show on his birthday. We've met some adults with this condition now and they'll tell terrible stories about the types of injuries they've put up with because they didn't want to not go on a school trip or appear unusual, and yet they'd have broken major bones and not be able to stand up. They'd have burnt their lips on boiling water.

Chris - They'll do things like walk on fire, and literally do it without any jiggery pokery or tricks. They can walk on hot coals and things.

Geoff - They will and they won't feel pain, but they'll do as much damage as if you did it.

Chris - So we've proved that it can be bad if you have all your pain turned off all the time, but it strikes me that you've found something incredibly interesting because there are lots of people who in their lives have to go through incredibly painful things. Anaesthetics are not brilliant, are they? They're very non-specific, they cause lots of side effects and if you take things like morphine or heroin for pain killers they can switch down your heart and breathing so that people die of heart and respiratory depression. If you've got something that has the power to inactivate just this part of your nervous system, can we exploit that to make an amazing drug?

Geoff - I certainly hope so.

Chris - You have a patent on it already I suppose!

Geoff - No we don't have a patent on it at all. We haven't exploited this result at all and are interested in it academically. Others hopefully will and I know that drug companies are already looking at this sodium channel and many other similar ones. The hope is that if people who have none of this protein feel no pain but don't have other side effects, then if you block this protein in a normal person, they'll have a pain killer without side effects. That's exactly the hope that drug companies are now working on.

Chris - Is that feasible?

Geoff - We think so. The problem is that there are about eleven of these sodium channels and they are very similar to each other. So the problem's going to be getting drugs that are totally specific to just one of these sodium channels and doesn't spill over and block other sodium channels.

February 2007

Dealing with Pain

Chris - We've been mentioning this question of phantom pain for a while, but what actually is it and why does it happen?

Cathy - Well phantom limb pain is pain in a body part, in this case a limb, that is missing. Although there are some reports in pain in congenitally missing limbs, so people who've never had limbs, it's much more common in people who lose limbs in later life. Phantom pains do occur in other body parts, so there are phantom tooth pains and phantom bowel pains for people who've had bowel surgery, but by far the most common phantom pain we see id phantom limb pain.

Chris - How can we actually treat it? Because it's easy to understand if there's a part of your body that's damaged and you can put some drug on it to make it feel better. That's intuitive. But if the part of the body that you can feel hurting isn't there, what can you do about that?

Cathy - Well I think the interesting thing about phantom limb pain is that it reflects the complexity of all persisting pain syndromes, which is that a lot of the signals that give rise to the perceptual experience of pain actually arise within the nervous system itself. So obviously if you have a hand missing and you have a painful hand, the signals are obviously not coming from the hand. But you've got to remember that sensory information from the hand involves all sorts of processes up to the cortex and other parts of the brain, and when the hand is missing, the rest of that circuitry takes over to generate sensations. In answer to your question to how we treat it, the answer is that we're not very good at treating it. The condition was described about 500 years ago and we know masses about the neurobiology of the nervous system and the psychology of it, but we're not much better at treating it than ever we were.

Chris - Now that aside, that's obviously a kind of chronic pain, but we can think of pain in two sort of arms can't you. You've got acute pain, which is when you hurt yourself and you have pain now, and then you get chronic pain, which goes on and on forever. Why are the two different?

Cathy - They are different and the definition is really one based on time, so it's pain that's persisted after you'd expect healing to have taken place. But really they are two different types of phenomena. Acute pain, as you said, is expected pain or an everyday pain. So of you stub your toe against the door you'll get acute pain, or if you burn your hand. Commonly in hospitals we see acute pain following surgical procedures. The circuitry for how we process acute pain is fairly well known, fairly well mapped out and fairly predictable, and usually one or at most two treatment interventions are likely to get rid of acute pain, and it has a favourable natural history. It also has an important warning signal for people injuring themselves. With chronic pain it doesn't have that same warning signal function, and it's also much more complex in terms of the circuitry involved. It's very unusual for a single type of treatment to treat chronic pain and we usually have to use a raft of different therapies to treat it. Many chronic pains are resistant to therapy.

Chris - What are the consequences of living on pain killers, because doesn't your body become slowly less responsive to those agents? Do you become immune to those effects if you like, which means that you have to take bigger and bigger doses until in the end you can't take a bigger dose and so you get pain again?

Cathy - You're describing a phenomenon that we call tolerance and exactly as you say, it's your body getting used to a drug. Not very many drugs are associated with true tolerance. The most common ones are the opioid drugs morphine, where any normal person taking these drugs over a period of time will find that they need to take bigger doses to achieve the same analgesic effect. Other drugs aren't so much associated with tolerance, but I guess people sort of seem to get used to it and almost seem to reset their own thermostat if you like. Once they've been on drugs for a while they maybe forget how helpful they've been, and often we see in a clinic patients coming in who've been on drugs for many years and comment that they don't help at all. But when they stop them, the pain is indeed worse.

Chris - What about new fangled things that science has been able to throw at people with chronic pain in recent years? Electrical implants and things like that.

Cathy - That's a very interesting area that we call neuromodulation and the idea is that by electrically stimulating parts of the nervous system with very clever systems that can be completely internalised, one can modulate the sensory experience. The commonest of these in the UK is a treatment called spinal cord stimulation where we insert an electrode next to the spinal cord and elicit a pleasant tingling sensation in the painful part. This seems to override the pain message. That's quite difficult and one often can't elicit a tingling in a phantom limb, so spinal cord stimulation is maybe less useful for phantom limb pain than other techniques. There's some other research coming out of Oxford and we're starting to do some in Bristol looking at stimulating parts of the brain to treat phantom limb pain, and there are some promising early results. But of course these are quite invasive procedures that have not insignificant risks of their own.

February 2007

What Chillies have in common with Taratulas

Chris - Now talking of pain, David Julius is on the line. He's not a pain but he works on pain at the University of California in San Francisco. You've made some very interesting discoveries regarding the relationship between what comes out of a chilli and what comes out of a tarantula. Tell us about that.

David - Well what we found several years ago is that chillies have their hot and spicy bite, which has been known for many years that that's caused by a main pungent in chemical or ingredient in the chilli called capsaicin, and what we showed was that capsaicin acts on a specific molecule on the surface of pain sensing nerve fibres. In doing so, it activates those nerve fibres and gives the sensation of burning pain.

Chris - So that's why if you eat a curry you get this burning sensation in your mouth, because you're fooling the brain or the nervous system's pain pathways into thinking you're being burned.

David - Exactly.

Chris - So why should there be this chemical overlap between the real burning, so someone holding a cigarette lighter to your finger, and say eating a chilli?

David - Well I think in the case of the chilli and what I think we'll be coming to in a minute, the tarantula, all of these organisms have usurped this pathway and taken it over as a way of conveniently using this system as an anti-predatory mechanism.

Chris - So the chilli wants to stop itself being eaten?

David - Yes by something like a ground squirrel or a predatory mammal. So presumably nature has endowed it with the ability to make these compounds that have evolved to activate our pain pathway as a way of saying keep away. They have done this by targeting a specific molecule that we believe is involved in sensing heat. And so the psychophysical sensation is similar because it's activating the same neural pathways. Both of those stimuli are activating the same neural pathways that tell our brain that we've touched something hot or experienced something that we have come to know as being hot or of that ilk.

Chris - Now you mentioned something interesting when you were talking just know. You said mammals and ground squirrels. Are you saying that not all animals are sensitive to the effects of chilli or capsaicin?

David - That's right. Not all animals are, and in particular birds are relatively insensitive to capsaicin.

Chris - Why?

David - I think it's because they have again found their ecological niche as vectors for dispersal of the pepper seeds. In addition to not being sensitive in terms of pain lines being sensitive to capsaicin and this burning sensation, their digestive tract does also not destroy the seeds, so they're well suited to eat the pepper plant and disperse the seeds as a way of carrying out germination of the plant.

Chris - So when people say that a good way to stop rats from nicking your chicken's food or to keep squirrels off your bird feeder would be to cover the nuts with a healthy lashing of chilli.

David - Yes, well people do that and can buy seeds that are laced with capsicum dust. I have trouble with squirrels in my bird feeder too and I have to try that. I'm told that eventually the squirrels will adapt and ignore the hot pepper on there but I have to try it myself.

Chris - Because there's some evidence that people who regularly ingest very hot curry become a bit less sensitive to its effects. Is this because it's damaging the receptor or is it damaging the nerves? Are their mouths becoming less sensitive to pain, or is it just that the target for the chilli is being reduced in density on the surface of the nerve fibre?

David - I think it's probably all of those things. Capsaicin, when applied to a sensory nerve fibre, will cause some destruction or temporary desensitisation of the nerve fibre ending. You can see this in rodents as well as in man, so there is some what we call functional desensitisation of the nerve fibre and in some cases even anatomical damage. Of course, those fibres will regenerate and grow back. I think in the case of people there's also a psychophysical desensitisation in a way that if you've been eating kimchi or something spicy ever since you were three or four years old, not only do you come to appreciate it, you also get used to the burning sensation.

Chris - Now one thing that does produce a burning sensation though is the tarantulas you've been looking at. Tell us about the link between chillies and those.

David - We asked a little while ago why is it that bites and stings from some venomous creatures are associated with acute and intense pain. Not much is known about that, so what we did was to carry out biochemical fractionation of venom from a number of spiders and asked whether there was something in those venoms that was particularly potent in activating the receptors the we and other labs have identified as being important players in initiating pain in nerve fibres. We identified this one spider from Trinidad and Tabago called the Trinidad Chevron, and in its venom is a small protein, three of them actually that we identified.

Chris - And they activate the receptor.

David - They target the same receptor that the hot chilli pepper targets.

Chris - Now we're very short for time, but could you tell us in about twenty seconds why it is that when I suck on a polo mint it makes my breath feel cold?

David - For the same logic that hot peppers make you feel heat. So that is that the mint acts on a receptor that's activated by cold and so it tickles the same signalling pathway through which cold tells your nerve fibres that you've experienced something thermally cold.

February 2007

Why sausages split lengthways

Although it's freezing in England right now, on the other side of the world the sun is shining. So in honour of the sun-drenched Antipodes, Derek goes for a BBQ at the house of our very own Ozzie Hugh Hunt.

What you need

A BBQ
Some very cheap sausages (the more expensive ones are designed not to split)
Willpower (you can't eat the sausages before the experiment is over!!)

What to Do

1 - Light a BBQ - ask a sensible adult to make sure everything's safe

2 - Throw on a few sausages and let them cook - Don't make holes in them

3 - Stand well back as we are hoping the sausages will split and when they do this they will  spit.

4- Keep an eye out for sausages with split skins. In which direction do they split?

What may Happen

Sausage skins split lengthways down the sausage much more often than they split around the sausages.

What is going on?

You can think of a sausage skin as being like a pressure vessel. It's actually holding in all the contents that are expanding with the heat. When the skin suddenly bursts, it's going to burst in the direction where the stress is highest. The stress is really just the amount of tension there is the skin. It turns out that for a pressure vessel, the stress going around circumferentially is twice as high as the stress going lengthwise. So that means that it tends to rip along the length because the circumferential stress is twice as high as the longitudinal stress. The same thing happens when you put a can of beer or a can of coke in the freezer: it will also burst along its length.

We can see this effect in other ways too. For example, you have gas pipe lines going thousands of miles across Alaska - a bit like a giant sausage. The one thing you have to be really careful about is that you don't get a burst pipe. If it starts to burst, the burst will go right along the pipe for hundreds of miles. The people in the know will say that the pipe is 'unzipping'. It's absolutely catastrophic because it releases gas over a large area.

But going back to our sausages - the best way to prevent them splitting is poking them, but that lets out all the delicious juices. So you really want to find a compromise, and this is to cook them at a nice gentle rate so they don't burst.