Science gets under your skin on this week's Naked Scientists, where we find out how human skin colour evolved to make the best of our sunlight. We explain why albino people have no skin pigment at all and how to heal wounds without leaving scars. Also, the nano-scale media storage that will last a billion years, the toxic bite of the komodo dragon and the biological link between cancer and depression. Plus, we shine a light on jaundice phototherapy, with the help of a urinating glass baby!
In this episode
Data storage that will last a billion years
Scientists have used nanotechnology to solve a serious problem of the digital age - data degradation.
Although we think of digital storage as a way to preserve photos and other data in pristine condition, the lifetime of modern storage media is as little as 20-30 years. This is in stark contrast to the enduring properties of the stone tablets on which some of the world's oldest writing remains readable 4000 years after it was first carved and the fact that the Domesday Book, at the age of 920, is still going strong.
The modern equivalent, however, which was commissioned in 1986 by the BBC, had to be migrated to alternative media twenty years later because the original laser discs on which the material was stored had failed.
But what sets ancient media storage systems apart from the more modern counterparts is the data density. Stone tablets contain about 2 "bits" of information per square inch compared with contemporary digital devices which store about 100 Gigabits per square inch - 50 billion times more. At these scales, however, the storage medium is not reliable and the integrity of the data is cannot be preserved in the long term.
But to solve the problem, University of California Berkeley researcher Alex Zettl and his colleagues say they've developed a system that should last at least a billion years, within reason. Their approach is to use short nanotubes - tiny molecular straws of carbon - inside of which they place an iron-based nanoparticle "shuttle" that can move up and down the inside of the nanotube. When a small electric current is passed through the nanotube it causes the iron shuttle to slide from one end of the tube to the other.
This, say the team, can be used like a binary digital storage system with one end of the tube representing a nought (0) and the other end a one (1). The position of the particle can be read-back from the nanotubes by measuring their resistance, which changes according to the position of the iron shuttle.
The small scale of the devices also means that storage densities in excess of 1 Terabit per square inch should be possible, more than 10 times the present achieveable. Better still, simple calculations based on the stability of the system and the likelihood of the iron shuttle randomly moving the 200nm length of the tube to turn a 0 into a 1 or vice versa mean that the data should remain reliably preserved for at least a billion years, or 1017 seconds!
Dragons with toxic bite
They seem like the stuff of fairytales or maybe nightmares, but Komodo dragons are the closest things we have to real, man-eating dragons. At three metres long, these lizards that live on the Indonesian island of Komodo and are fearsome enough, and now scientists have discovered that they have a toxic bite. Until now it was thought that the key to their deadly bite was bacteria in their saliva which infects their prey, causing them to go into shock before the dragon returns to kill and eat their victim.
But now, Stephen Wroe from the University of New South Wales, Australia and a big international team of researchers publishing in the journal PNAS have discovered that Komodo dragons have venom glands containing a dose of anticoagulant toxin that causes their victims to bleed to death.
First the team used computer models to analyse the skull of Komodo dragons and found that they have a much weaker bite than crocodiles of a similar size suggesting that instead of biting down hard they are better suited to holding onto prey that is trying to wriggle away. The team then put a preserved head of a komodo dragon into a magnetic resonance scanner and discovered a set of complex venom glands in its jaw with ducts coming out of their teeth.
The researchers surgically removed a set of these glands from a terminally ill dragon in a zoo. Using mass spectrometry they worked out the chemical make up of the venom and discovered it is made up of a complex mix of proteins, similar the lethal cocktails used by other venomous reptiles.
These toxins induce shock in victims causing them to bleed copiously by preventing blood clotting and widening blood vessels. That finding fits with reports from humans who have been bitten by Komodo dragons and continued to bleed for a long time afterwards.
The researchers also examined the fossil teeth of an extinct relative of the Komodo dragon, called Megalania, and discovered that this two tonne, seven-metre giant probably also had venom glands, making it one of the largest venomous animals ever known. But don't worry, these monstrous lizards haven't been around now for 40,000 years although their smaller cousins the Komodo dragons are undoubtedly impressive predators and now we have a much better idea of how they deal their lethal blows.
Down's do better in cancer stakes
Individuals with Down's syndrome have a significantly lower likelihood of developing cancer (with the exception of a form of leukaemia) compared with the general population but no one knew why. Now a study in the journal Nature has revealed the answer.
Harvard researcher Sandra Ryeom and her colleagues have found that one of the 231 genes on chromosome 21, of which Down's patients carry an extra copy in all of their nucleated cells, controls blood vessel development. This suggested to the team that part of the cancer-preventing effect in Down's might be because cancers find it more difficult to produce new blood vessels to support themselves.
The clue came from the observation that Down's patients also have lower risks of developing diabetic eye disease, which is caused by the growth of new blood vessels in the retina, and vascular disease in general.
As a result the Harvard team focused on a gene called Dscr1, which encodes a cellular off-switch that suppresses the effects of a blood vessel growth factor gene called VEGF (vascular endothelial growth factor).
The researchers implanted cancer cells into mice genetically engineered to have the rodent equivalent of Down's. Compared with control animals the cancers in these mice grew significantly less well. To prove that Dscr1 was responsible for the effect the team then removed the extra copy of this gene from their Down's mice and repeated the experiment. As expected, the tumour-protective effect had largely disappeared.
However, as the researchers point out, there are 230 other genes on chromosome 21 and one or more of these may also be contributing to this effect. But regardless of this, the present results confirm that Dscr1 has a powerful anti-cancer action achieved through suppressing the growth of new blood vessels that are needed to sustain solid tumours.
According to the researchers "it is, perhaps, inspiring that the Down's syndrome population provides us with new insights into mechanisms that regulate cancer growth and, by so doing, identifies potential targets for tumour prevention and therapy."
Brain structure makes a people-person
Do you consider yourself to be a people-person? Do you crave the company of others, are you warm and sentimental? Well, if you are, then it could come down to the structure of your brain.
Graham Murray led a team of researchers from Cambridge University and Oulu University in Finland who have discovered that the greater the concentration of tissues in certain parts of the brain, the more likely someone is to be highly sociable. Earlier studies have linked these same areas of the brain to processing simple rewards like sweet tastes and sex.
Publishing in the European Journal of Neuroscience, Murray and the team recruited 41 male volunteers who had their brains scanned by MRI scanners and were also asked to fill out a questionnaire to find out about aspects of their personality. They were asked to rate themselves on statements like 'I make a warm personal connection with most people', or 'I like to please other people as much as I can'. The results of the questionnaire provide a measure of how sociable someone is, called the social reward dependence.
They found that people with higher social reward dependence scores tended to have a greater concentration of grey matter in both the orbitofrontal cortex (the outer strip of the brain above the eyes), and in the ventral striatum (a deep structure across the centre of the brain).
Eating energy-rich sweet foods and sex are vital for survival while social interactions are not necessarily so, but it could be that emotions like sentimentality and affection in humans evolved from structures in the brain that make animals seek out and satisfy these more basic needs.
This research could also shed light on understanding what causes various psychiatric disorders which make social interactions difficult, like autism or schizophrenia. So far Murray and his team have found a correlation between brain structure and personality, but exactly how the two are linked is still to be uncovered.
13:30 - Biological Link between Cancer and Depression
Biological Link between Cancer and Depression
with Dr Leah Pyter, University of Chicago
Chris Smith: Now also in the news this week, researchers at the University of Chicago have identified a potential biological mechanism that can link cancer with depression, and we are joined by Dr Leah Pyter to tell us a bit about it. Hello Leah?
Leah Pyter: Hello!
Chris Smith - Welcome to The Naked Scientists! So do tell us, what is the evidence then that people who get cancer get depression, because obviously that's a pretty traumatic diagnosis to receive. Are you saying then that people get depressed before they get their diagnosis of having cancer?
Leah Pyter: Well basically what we know is that patients with cancer have a higher likelihood of also developing depression at some point in their disease progression, so whether that occurred before and is predisposing them to cancer, or it's due to the tumours themselves, or other aspects of having the disease, we don't know. We were only studying right now whether the cancer itself can cause depression.
Chris Smith: How could a tumour trigger depression, because a tumour can occur anywhere in the body, therefore at the remote sites in the brain, so how could it trigger changes in brain activity?
Leah Pyter: Sure, well what we hypothesized was that the tumours themselves can produce cytokines which has been shown before.
Chris Smith: These are inflammatory chemicals that drive the immune system?
Leah Pyter: Right, exactly! And there is also a pile of research on how cytokines can access the brain specifically regions of the brain that are associated with depression and anxiety and emotional behaviours, and they can access the brain both tumourally through the blood, or neurally through the vegas nerves.
Chris Smith: So what did you actually do to get to the bottom of how cancer might be able do that?
Leah Pyter: First of all, we are using an animal species, rats, in order to isolate just the physiological impact of having a tumour from the psychological impact of having the disease. We induce tumours in rats and had controls, and then looked their depressive and anxiety-like behaviour along with some physiological measures of these cytokines and the stress access.
Chris Smith: So you'd give rats the cancer. Can you show that when they get the cancer they do develop a sort of depressive or anxious-like syndrome consistent with having - or contemporaneously with having the tumour?
Leah Pyter: Exactly, yes! That's what we did - basically we used standard behavioural tests in these rats that have been used to develop pharmaceuticals, like antidepressants and you have control animals and we measured these types of behaviours and made sure that they only developed following the presence of a tumour.
Chris Smith: And once you'd confirmed that the rats do seem to get depressed when they get a cancer, how did you then find out what was going on to make them feel like that?
Leah Pyter: Well, we had two candidates, one were the cytokines that we have some information about associating with depression, and the other was via the hormone access that regulates stress responses; and so we were able to measure cytokines in the tumours themselves, in the blood as well as the brain in animals with and without tumours, and we also measured one of the stress hormones in response to a stressor and found that cytokines were increased in the brain if you had a tumour and your hormone response to a stressor was dampened if you had a tumour, relative to controls.
Chris Smith: So the cancer is definitely inducing biochemical changes in the brain that might trigger depressive symptoms. We can treat depression though. Why is it important to have identified this problem, and how can it help us to make people who have cancer have a better outcome?
Leah Pyter: Right. So I think one of the things we were keying in on is that a lot of chemotherapies are cytokine-based and so if you're having a patient that is displaying depression along with the cancer you might try to switch the chemotherapies but it's also important because cancer patients that are depressed are less likely to stick to their medical programme and are more likely to succumb to the disease. So not only treating the cancer but also the depression is important for their wellbeing.
Chris Smith: Thank you very much. Leah, thank you for joining us! That was Dr Leah Pyter who is at the University of Chicago, she and her colleagues have published a paper in this week's edition of the Journal, PNAS, in which they explained how things like cancers can change the behaviour and particularly to cause behaviours like depression, which as she just explained, can have a major impact on how well someone does in terms of their therapy and their long term prognosis
19:39 - Could the dragon venom be used as an anticoagulant for humans in small doses?
Could the dragon venom be used as an anticoagulant for humans in small doses?
Chris - Well the answer is Troy-yes, people are very interested in this very question, and also from borrowing from biology using the venoms from other creatures that have anticoagulant properties. For instance, people are looking at the genes that come out of leeches. They've got a drug now called Hirudin which is a protein that stops blood coagulating by stealing what leeches use. This same thing could be used because we are always looking for ways to thin blood in a slightly less damaging way than using things like Warfarin, which does have side effects. So I suspect that there are certainly scientists right now who are looking at that very question.
20:15 - Albinism - Why Some People have No Skin Pigmentation
Albinism - Why Some People have No Skin Pigmentation
with Dr Lester Davids, University of Cape Town
Lester Davids: The skin is made up of a number of cells, but two predominant cell types:
· The melanocytes which are the cells that produce melanin which actually colour our skin.
· And also the keratinocytes which form the upper layers of our skin, and are really just there to increase the layers to protect our skin against all sorts of injury.
So the melanocytes are probably more important because they are the ones that give us the colour that you actually see. So it's the first thing that you see really, and so we need to look after the melanocytes and the keratinocytes because it is from those if something goes wrong with those cells they cause all types of skin cancers.
Meera Senthilingham: Why is our skin protective? Why is it important for us to have it?
Lester Davids: The skin is the largest organ of the body. It is not only in the sensitive to touch and to the external environment, it is the first level of defence of our body that actually reaches the external environment. So in that sense, it is obviously very, very important for protection. The problem is that most of our skin - well, a large proportion of our skin is exposed to the elements all the time; and so we need to have an idea of how to look after our skin. Although your skin may be a different colour it doesn't mean that it is much more or much less protected because of that colour. In general, the same rules apply--how you protect your skin.
Meera Senthilingham: Now, another thing you look into is diseases and disorders that affect our skin. So which of these do you look into?
Lester Davids: The one condition that often occurs is the genetic condition called albinism. Because it's genetic, you're born with it and the problem with it is that melanocytes are actually absent in the skin, or the enzyme that produces the melanin is absent, and so the skin is completely pale because it lacks pigment, and that is obviously a problem because lighter skin is a little bit more susceptible to UVA damage or to sunlight damage. The cells that produce the melanin are also found in our eyes, and if you don't have those cells your eyes become very sensitive; and so albinos, besides being ostracised in some of our communities in South Africa and in southern Africa, they also have very sensitive eyes and they need to look after that.
The third place that the melanocytes are missing is in the hair and so they have red or very light-brown hair and that also needs extra protection because they don't have melanin. So they normally wear headgear or head covering.
The other condition which is non-genetic but can be caused by a variety of factors, including oxidative stress--stressing out, is called vitiligo, and here the melanocytes are predominantly disappearing and so we get large patches of non-melanized areas of our skin which are white. If your skin is a bit dark that looks very contrasting and people often think that they have a contagious disease which is absolutely incorrect. It is just the melanocytes that are not there. The nice thing about vitiligo, the non-genetic condition, is that there is treatment available and these days if you see a very good dermatologist they can recommend treatment and re-pigmentation can occur after the treatment, or after several bouts of treatment.
Meera Senthilingham: What does the treatment involve in order for someone to get their colour back?
Lester Davids: In vitiligo they give them a psoralen which is a photosensitizer and then they shine UVA light on them. That photosensitizes the skin and also photosensitizes the melanocytes or the stem cells of melanocytes that are left, with a result that those cells divide and they start to re-pigment. The nice thing is that in hairy areas the stem cells or melanocytes sit in a niche around the hair follicle and this treatment--the psoralen plus UVA stimulates them to start producing melanin, and so these patients, fortunately for them, if they respond, they will start to re-pigment and actually get the colour back.
Meera Senthilingham: Now looking more into albinism it's a genetic condition but is it inherited? Is it due to mutations? How does it actually happen and what genes does it affect?
Lester Davids: Albinism comes in a variety of different types, one of the common most ones in southern Africa is called ocular cutaneous albinism. This is a genetic defect in the enzyme called tyrosinase, and tyrosinase is the enzyme that the melanocyte uses to produce melanin. So that enzyme particularly is not working properly, and so no melanin is produced; and these days with gene therapy on the increase, if there are lots of research happening where they're actually looking at trying to correct that genetic defect, because it is in fact the way that tyrosinase is made, inside the cell, and where it actually moves to inside the cell that has been blocked; and so you don't get tyrosinase, the enzyme, doing it's proper job, and so you get a lack of pigment.
Evolution of Skin Colours
with Professor Nina Jablonski, Penn State University
Some people are white, some people are black, some people are in-between. But where did all that originate and how do we end up with all the races that we have on Earth today? Joining Chris Smith to shed some light on this is Professor Nina Jablonski who is an anthropologist at Penn State University.
Nina Jablonski - Hi Chris! It's great to be with you.
Chris Smith - It's good to have you with us. So - tell us - actually why do we have different skin colours? What's the point of it?
Nina Jablonski - Different skin colours are due to different levels of the pigment melanin in the skin, and people at the equator or close to the equator tend to have a lot of melanin in their skin and people distributed farther away from the equator have considerably less.
Chris Smith - But what do we know if we look back in history, about how that came about? Because obviously we know people who live in my part of the world where we hardly see the sun one week in ten, compared with people in Africa where it's very sunny. What do we know about how those two systems of people evolved?
Nina Jablonski - The earliest members of our species evolved in equatorial Africa and had high levels of melanin pigment in their skin which protected them from the very deleterious harmful effects of ultraviolet radiation in the sun; which is present at great concentrations close to the equator. But as people in our species dispersed over the course of the last 50,000 years we dispersed into areas that had much lower levels of ultraviolet radiation, necessitating a loss of skin pigmentation. So you and your ancestors living in Britain are actually depigmented people compared to original members of our species.
Chris Smith - But why do we need dark skin - what actually is the pigment protecting us from? What is the sun doing? Because obviously we've all heard of skin cancer and the fact that there is this association between sun exposure and skin cancer; but is that the whole story?
Nina Jablonski - Not at all. Melanin pigment is tremendously good at absorbing and scattering ultraviolet-A radiation--long wavelength ultraviolet radiation, that destroys folate. Folate is a B-vitamin that is critical for the production of DNA; and DNA, as you know, is essential for new cells, for dividing cells, and so melanin protects against destruction of the cell division mechanism. So this is very, very important because it allows for instance early embryos to continue to undergo rapid cell division in a very precise way, lots of cell proliferation is going on and that is essential to survival. So melanin protects your cell division mechanism.
Chris Smith - But as I move away from Africa and go to climes like Britain where we have much less sun exposure, what's the point of going white? Why don't I just stay dark, because then I won't break down my folate and I won't get skin cancer?
Nina Jablonski - The reason that your ancestors underwent loss of pigmentation is that you still need to make vitamin-D in your skin. Your skin not only protects you from a lot of stuff but it's a vitamin factory, it makes vitamin-D. As you get farther north, the farther away from the equator, up where you are living, you get about two months during the year when you have ultraviolet-B radiation in the atmosphere that can cause vitamin-D production, you'd need to lose as much pigment as possible to take advantage of that very rare UVB; and that's why you and your ancestors look the way you do.
Chris Smith - So that explains what the benefit to me of living at the latitudes I do, of being white is, but what about if we wind the clock right back about six million years or so to the ancestor that precedes both humans and our closest living relatives, chimpanzees -
Nina Jablonski - Yes!
Chris Smith - What colour would that ancestor have been?
Nina Jablonski - Almost certainly we can be assured that that ancestor would have probably looked a lot more like chimpanzees than us. The ancestor would have had lightly pigmented skin covered with dark hair. When you look at all higher primates including chimpanzees, the rest of the apes and Old World monkeys, all of our closest cousins--this is the pattern that we see, light skin covered by dark hair; and what's interesting is that all of these animals have the ability to develop a tan on the exposed parts of their skin. For instance, on their faces, and on their hands, so that that ancestor probably would have had the same ability to develop a tan on the exposed areas.
Chris Smith - It's intriguing to think that we were white, went black, and that some of us have gone white again. Why did we lose our hair though? Why didn't we just keep the hair if that worked well for that ancestor, and stay white?
Nina Jablonski - Well, hair is a wonderful thing to protect and insulate us, but also it impedes our ability to lose heat when we're exercising vigorously. One of the things that primates do to keep cool is to sweat, and if you sweat a lot into a very hairy coat, you can't keep as cool as if you sweat onto a naked surface; and so we think now that we lost our hair in order to become better sweaters and to lose more of our body heat through evaporative cooling from sweating. So basically our ancestors probably lost their heavy coat of body hair, probably around two million years or so ago, and at the same time as we did that we increased the number of sweat glands, the output of the sweat glands, so that we are really prodigious sweaters compared to all other mammals, and we also at the same time gained our dark pigment in the skin. All of these things occurred more or less simultaneously.
Chris Smith - There have been some times when I've been standing on the bus next to someone I wished hadn't gained the ability to sweat. But talking of hair, what about the stereotypical Afro-Caribbean hair. What is the benefit of having hair like that? There must be one of having very short compact, but very curly hair--very dense curly hair like that? What's the evolutionary benefit of having that?
Nina Jablonski - Well we have not done the number of experimental studies that we would like to, but certainly we can look at other animals who have similar configured coverings of their skin and what we see is that this curly covering of hair, or feathers in some vertebrates, actually protects the skin from excessive heat, and it does it by this mechanism. The very external surface of the hair becomes very hot when you're under the sun, but that external surface then leaves a cooler barrier layer of air between the surface of the scalp or the skin, and the very surface that's being heated by the sun; and that cooler barrier layer is critical because it allows the scalp or the skin to lose heat by radiant heat loss as well as by sweating. So basically, this curly, frizzy hair keeps a lot of loft in it even when it's moist, and thereby maintains this barrier layer that keeps our heads cool.
Chris Smith - Which is good news if you live in Africa. But if you are a member of say the Indian Subcontinent where it's equally hot, but you have straight hair, how does that sit with that?
Nina Jablonski - Well, actually as long as there is some kind of barrier layer, it still will work, although not quite as well; and what's really interesting is that there are some people in the southern part of the Indian Subcontinent as well as in Melanesia who have curly dark hair that was probably evolved independently from the ancestral condition of curly dark hair.
34:42 - Healing Without Scars
Healing Without Scars
with Professor Paul Martin, Bristol University
Helen Scales: This is The Naked Scientists and we're talking about skin, that wonderful stuff that keeps up healthy, keeps us dry. Comes in all sorts of colours, and one of the things that skin does very well, if all goes well, is it heals if we cut ourselves. What happens when skin cells are traumatised is that cells called fibroblast--produce fibrous tissues made of collagen and that helps close up the wound, but inevitably a little bit too much fibrous material is produced and that can lead to scarring. Well, now a team at Bristol University has discovered how these fibroblast are turned on by another class of inflammatory cells called macrophages and if the signal between the two is blocked it's possible to make wounds heal, with much smaller scars.
We sent Ben Valsler to Bristol where he met Professor Paul Martin.
Paul Martin: When our skin is damaged, wounded; fallen out in a scratch--our knee, or something, a whole cascade of events is initiated. Very quickly you forms a scab, and underneath that scab the tissues are trying to repair the hole in the skin, and there are several layers to the skin: the upper layer is epithelial layer and that's got to crawl forwards and close over.Beneath that there is a layer called dermis or connective tissue, and that tissue when it repairs, repairs with a scar.
So this response to tissue damage repair is not perfect. It turns out the reason we form a scar in that dermal layer--the reason we contract the connective tissue down is because inflammatory cells, white blood cells, rush out of blood vessels by the wound to kill bugs. As well as doing that, they talk to the wound fibroblast, and it seems that one of their conversations is just like a bad bi-product of their normal job, is to tell these fibroblasts to form a scar. So what we attempted to do was to figure out what that conversation was and what, in molecular terms, the fibroblasts did in response to hearing that conversation; and we identified as a hot candidate, a gene called osteopontin. It looks as though it screamed on in wound fibroblasts when they saw inflammatory cells.
We had a mouse that didn't raise a big inflammatory response, and when that happened that mouse healed its wounds without a scar, and didn't switch on the gene osteopontin. So there's a correlation: inflammation osteopontin; osteopontin scar, but that's only a correlation. It doesn't prove osteopontin is the bad boy. So what a Japanese post doc, Ryoichi Mori did, was to knock down in a normal mouse, this gene osteopontin; he knocked it down by delivering in a pluronic gel--this is a gel that's liquid at cold temperatures. As soon as you apply it to the body--to the mouse wound--37º, it hardens up, fills the would gap and oozing out of it is an antisense oligo which knocks down this gene osteopontin.
When he did that he found that these wounds that should have scarred; didn't. So that now demonstrated the correlation, osteopontin scar, was functional. That osteopontin was the reason they scarred. So then Tanya Shaw, another post doc in my lab, what she asked was, what are those inflammatory cells telling the fibroblast that makes the fibroblast switch on this gene osteopontin which leads to scars? So she knew that there were a whole list of growth factors that macrophages are known to make. So she took some fibroblasts in a dish and she threw all of those factors, one at a time, on to those fibroblasts until she found one that caused the fibroblast to scream on osteopontin. She identified one factor, PDGF: platelet-derived growth factor that looked as though it could do the job.
But the sort of - the real tasty bit of experiment was she then bathed the fibroblast in an antibody that blocks PDGF, and then she applied macrophages to the fibroblast, so those macrophages now pump out all the signals that they normally make in wounds, but the fibroblasts did not respond by switching on osteopontin. So that proved that macrophages are talking to fibroblasts via this signal PDGF and that was what, in a wound situation, was telling fibroblast to switch on osteopontin; and osteopontin was causal of scarring.
Ben Valsler: So just by watching what happens with different chemical messengers and different genes being activated, you actually were able to spot several different angles of attack, in order to allow wounds to heal healthily but prevent scarring. But what does osteopontin do in healthy, normal, non-wounded tissue? Are we running the risk of blocking a gene that's actually quite important?
Paul Martin: We absolutely are. My own impression is--and this is why you need to do, you know, very careful, gentle clinical trials. Certainly in the mouse experiments that we've done these wounds that have been treated with an agent that blocks osteopontin, heal the wounds better, faster and without scarring. Whether that will translate into the clinic isn't clear, whether there will be some downstream problem isn't clear, I can't even guess the sort - Now, you asked what it does, you know, what the function of this gene is? Well it's called osteopontin; osteo-bone--it's involved in bone cell development in the early embryo. It has some signalling roles in immune cells, many of these multiple roles it has might be involved in the wounding situation. We don't know and we need to look hard.
Ben Valsler: There are some situations where wounds will heal without scarring inside the mouth. They tend not to scar at all, and foetal tissue in fact gets will heal without scarring. Could we look at these situations to see if there are other pathways we could look at that perhaps wouldn't run the risk of blocking genes that might otherwise be useful?
Paul Martin: Good idea--look! We are a lab that comes from developmental biological. We are interested in how tissues are built and understanding how tissues are built in embryos gives you clues how they might be rebuilt in the adult. We are one of the labs that has shown that embryonic tissue doesn't scar. Embryonic tissue, when you damage it, doesn't raise a robust inflammatory response and we think that's one of the reasons why it doesn't scar, it's because there is no inflammatory cells turn up at the wound, osteopontin doesn't come on, so we're trying replicate what works beautifully in an embryo in an adult essentially.
Now you asked about the mouth and that is an interesting situation. You're right it is a place in the human adult body that repairs very efficiently, rapidly--not totally without scars but certainly they're reduced. Oral tissue has a much reduced inflammatory response, a different sort of inflammatory response. Maybe that's because the saliva in the mouth and in the saliva are anti-microbial activities and things, so you don't need such a robust inflammatory response.
Why do some people scar more than others?
Chris - It was a good question and we think inevitably it's down to overactivity of some elements of the immune system and some people make more of these gene products, that are being discussed between Ben and Paul Martin there, and it could be that this leads to more inflammatory response at the site of the wound, therefore more production of fibrous tissue by those fibroblasts and that's why you get more scar tissue. Of course you mustn't ignore the fact that if you get an infection in the wound as well this can prolong the time it takes the wound to form and that again encourages you to make more fibrous tissue.
Curing Infant Jaundice
with Professor David Phillips, Imperial College London
Chris - We sent along Meera Senthillingham to meet with David Phillips who is at Imperial College to do an experiment that many of us have done a few minutes after we were born.
Meera Senthilingam: On today's show, we're looking at skin and skin colour, and one colour babies can occasionally go, is yellow when they're suffering from jaundice; and it's long been thought that exposure to sunlight, or more specifically, the blue light in sunlight, can make this colour go away. So this week I've come to Imperial College in London to meet Professor David Phillips in the Chemistry Department.
Now firstly David, what actually causes Jaundice in a baby?
David Phillips: Well, we all have a turnover of red blood cells, we destroy the old ones in our body as we make new ones. When the old ones are destroyed they break down to a porphyrin molecule called Bilirubin. Bilirubin is a bright yellow colour and in its normal form it is fat-soluble, so it dissolves anywhere in the body where there is fat. Now in an adult we have an enzyme in our liver and bile which converts that fat-soluble bilirubin into a water-soluble form which allows us to excrete it but a baby does not have that enzyme because it doesn't need it in the womb because the mother does the excretion.
So when the baby is born, it has a problem. It is producing lots and lots of this yellow colour, bilirubin, but it doesn't have the enzyme and you have a lot of fat just under your skin so that's where the bilirubin goes and hence the jaundice.
Meera Senthilingam: Now you've got a very interesting experiment. We've got a glass baby here filled up to its thigh level with a yellow liquid. What's this yellow liquid then?
David Phillips: This is the authentic material which causes jaundice in newborn babies, this is bilirubin which is dissolved in a simulated fat solution, it really represents the jaundice in the newborn baby.
Meera Senthilingam: So what are we going to do now in this experiment?
David Phillips: Well first of all I'm going to give him a drink of water, because I want to show you that the bilirubin will not migrate into the water. It will stay in the fat solution.
So I'm going to lie him down--he is a very unusual baby, he drinks through a funnel and I'm going to insert the funnel into his mouth and then I'm going to pour in about 300 millilitres of water. Then I'm going to hold him up and you'll be able to see that the yellow colour stays in the fat solution, it does not go into the water. This is still water-insoluble bilirubin.
Meera Senthilingam: Yes, you're right. So the yellow fat solution essentially is still there. There are some bubbles on the top and then a clear layer of water on top of that.
David Phillips: So this baby has a problem. If he were left untreated, if it were a real baby, then this can lodge in the central nervous system and before the fifties it caused death in severe cases. Now what I'm going to do, is I've got a little hand-held ultraviolet lamp, which puts out actually quite a lot of blue light; and it's the blue light which is effective, because the yellow solution here, the bilirubin, in it's fat-soluble form is yellow, which means it's absorbing the blue part of the spectrum and the red part of the spectrum. Blue is more energetic than red and so it's the blue light which is the effective light.
So now I'm just going to do irradiate his legs with this blue light for about 2 - 3 minutes.
Meera Senthilingam: So whilst we wait for this blue light to have its effect, there is quite an interesting story as to how this was actually found out about in the first place.
David Phillips: Yes, it was an Essex Maternity Hospital and a nursing sister called Judith Ward, who is in the habit of taking babies out into the sunshine and stripping them down to their nappies, because she thought sunlight was good for them. On one occasion she took a baby back in for inspection on the ward by a physician whose name is Cramer; and when they took the nappy off this Caucasian baby they found that where the nappy had been, he was bright yellow; and so they both realised that sunlight must have converted the bilirubin in some way.
It was very quickly adopted throughout the Western world even though the chemistry was not understood.
Meera Senthilingam: Have there been any developments in understanding of the chemistry behind this?
David Phillips: What we know is it's a very fast reaction. That is, when the light is absorbed the reaction occurs immediately and the most likely candidate is what's called a cis-trans isomerization reaction. There is a carbon=carbon double bond which is locked in a particular position with substituents on the same side of the molecule; that's called the cis form. That represents the fat-soluble form of this molecule; and then when you shine the light on the molecule, it unhinges the double bond which leaves the molecule free to rotate to 180º and then the bond re-forms. Now you've got these substituents on the opposite side--that's the trans-configuration. In doing that you open the molecule up so it presents a carboxylic acid group which is water-soluble to allow the whole molecule to dissolve in water.
In the fat-soluble form that carboxylic acid is buried inside the molecule and so the whole molecule is hydrophobic.
Meera Senthilingam: Okay. So you've been irradiating the baby with the blue light for a while now.
David Phillips: Now what I have to do is to shake him violently to mix the two solutions up.
Meera Senthilingam: Okay. That's good!
David Phillips: Here we go! And now I think as the two solutions separate out I hope you will now be able to see quite clearly that the yellow colour has now migrated into the water layer, just through that photo-chemical reaction.
Meera Senthilingam: Wow! Now that really is extremely impressive. There's been a complete reversal; so up to the thighs which was previously yellow with the fat-soluble solution is now clear; and then the layer which was water above the thighs of this baby are now completely yellow, so it has been 100% reversal of the colour.
David Phillips: Mm-Hmm. Now this little baby can do exactly what you or I do -
Senthilingam - And he is excreting the yellow bilirubin via his urine.
David Phillips: You can now see that this is quite a good demonstration of something that actually occurs. Of course in hospitals you don't use sunlight to do this, we use an artificial blue light which fits over the baby's crib, and usually about a 30-minute irradiation is enough to convert the bilirubin.
Meera Senthilingam: So essentially, David, if a baby is exposed to blue light then, the bilirubin will be filtered out through the kidneys then and be excreted in the urine?
David Phillips: That's correct. In a water-soluble form then it drains away from the skin through the normal drainage processes in the body, down through the kidneys where it's filtered out and then from the kidneys into the bladder and then out in the normal way.
Meera Senthilingam: This treatment with blue light is temporary basically until a baby develops this enzyme that they need?
David Phillips: Yes, a kind of holding operation. A normal baby will develop the enzyme within a day. If a baby is born prematurely or with any liver malfunction, which is really very common, then it might take a lot longer for the enzyme to develop. It's therefore not any good for adults who have jaundice, because that's a clear indication that there's something badly wrong with the liver.
Meera Senthilingam: So this baby has now excreted its bilirubin out and it's now clear and healthy?
David Phillips: Yes, and with any luck, it's developing its enzyme and so it won't need this treatment ever again.
51:55 - Will the stupid outbreed the clever?
Will the stupid outbreed the clever?
We put this to James R. Flynn, presently at the Sage Foundation in New York, but normally a Professor at the University of Otago in New Zealand. The question of this dysgenic mating, and by that we mean that people with lesser education are having more children than people with more education, would, if it were universal and persistent, and not contradicted by anything else, probably be a problem over a period of 100 or 200 years. But it's not universal and countries where everyone has a middleclass lifestyle, like Scandinavia, and where you have real educational quality for everyone, you don't have this trend. Now you can always say, "is there any chance that countries like Britain, or America will achieve that degree of social justice, maybe they won't." But there is the Flynn effect, that is: well we might be losing one IQ-point a generation through dysgenic mating, we are picking up something like 9-points a generation due to environmental factors. Better schooling, more interaction between parent and child, a more cognitively rich environment. Now that may run out of steam eventually but we don't have any real reason to be concerned in the meantime. If IQ gains due to environmental factors stop happening and if we are silly enough not to make our societies more equal, then over a 200-year period you might start worrying about the fact that the brighter people aren't having as many kids.
Why are Inuit people dark skinned?
We put this to anthropologist Nina Jablonski...
Yes, there is a great contrast. Swedes evolved lightly-pigmented skin and light eyes and, due to a different set of genetic changes, people living at the same latitude, the Inuit people, in far North Eastern Asia and in Alaska have actually darker skin than we would predict, and dark hair.
Now the dark skin is very interesting, because the Inuit experience very, very, high levels of reflected ultraviolet radiation - long wavelength ultraviolet radiation - from the snow. So their dark skin actually protects them from this high amount of UVA radiation.
Their dark hair, we're not exactly sure, but almost certainly the dark hair of eastern Asian peoples was a consequence of small population effect: the genetic drift in the ancestors of all East Asian Peoples.
Chris Smith: So, Nina, with that in mind, do you also see increased pigmentation or re-pigmentation amongst seafaring people, because, of course, they'll get the incident radiation off the water surface?
Nina Jablonski: Yes, and many of these seafaring peoples are naturally very dark and they have an excellent potential for making more pigment in their skin. So yes, we need more genetic studies of these people so that we can better understand how their pigment systems work...
Were we wearing clothes as we moved out of Africa?
Nina Jablonski: Oh! But we weren't. About 50,000 years ago we were not wearing clothes. We probably had the ability to drape some skins over our bodies, but we certainly didn't have sewn clothes until about 14,000 years ago. So basically we were mostly naked; and occasionally covering ourselves up. One of the ways in which we kept warm also was we had a vigorous shivering response, so we would be able to huddle together, and shiver together to stay warm at night. But clothes came very late in human evolution. Chris Smith: Ideal for The Naked Scientists.
Would a base tan be best?
Nina - A basal level of tanning is a bit problematical because it costs a lot (in terms of your body) to make melanin. Melanin is a big pigment and where you need it. For instance, if you live in equatorial Africa you really need it. It's worth the expense. If you live outside of the tropics where there isn't a lot of sun then it doesn't pay off and so that's why in some populations you have the ability to tan but in very northern, Eurasian populations you don't have the ability to tan at all. There's so little UV. Basically, the body economises.
How did human races form?
Nina - Well, it's a big question and one can argue that there are no such things as human races, because human races are basically defined by us socially. When you go to Britain or the United States or Brazil or India there would be different groups that would be defined as different races. In many respects races don't exist. What we do see are lots of patterns or genetic variation. Some of these patterns are related to our appearance but those are just a tiny fraction of our genes that actually contribute to these differences in appearance. We have tremendous amounts of variation that don't coincide with these classic racial groups that have been defined in various places. The long and short of it is races are an outdated, ancient construct that we'd best ignore.
Does beta carotene help against sunburn?
Nina - Beta carotene probably has some beneficial effect by preventing damage to collagen as opposed to protecting as a sunscreen, per se. Because beta carotene, the precursor of beta carotene (retinoic acid) does influence collagen production in the skin. Taking beta carotene could, in fact, have some beneficial effect on stimulating collagen formation. Really, you don't want to get out in the sun and get that much ultraviolet radiation so that this reaction has kicked in, in the first place. You should protect yourself from the sun except for short or moderate lengths of exposure. Don't bask in the sun.
If Africa moved further south, how would we have evolved?
Nina - The rate at which Africa is moving south is very slow. I doubt that this really would have affected human evolution. The timescale of human evolution is very short compared to the timescale of movement of the African continent.
Is there more UV at the equator?
Nina - There is considerably more UV at the equator and considerably more UVA than UVB. UVA is the type of ultraviolet radiation that begins the process of vitamin D formation in the skin. There's a lot more UVA as well. At the equator you get bathed, absolutely drenched in UV. And it's quite a bit hotter. At other latitudes you get considerably less ultraviolet radiation, especially the short length UVB.
Do blood group diets work?
Chris - I guess we can ask this in two ways: One is - Where do different blood groups come from? And is there any evidence that eating a certain diet, if you have a certain blood group, has any kind of physiological evidence that it's any use?Nina - Well blood groups, of course, are related to the types of antigens, these proteins present on the surface of our red blood cells. We have, for instance, high concentrations of A blood type in Europe, O in Asia, B in the Mediterranean area and so forth. The problem is that you find lots of geographic heterogeneity in blood types, and so if you go to the circum-Mediterranean for instance you'll find not only B blood types, but A and AB and O as well. And so the idea of there being pure blood types in any one area is not very good. And, perhaps the most important thing is because of this these blood type related diets, basically, are rubbish. In any given geographic area, there will be people with various blood types that will have shared other aspects of their environmental history. For instance, many people living in Britain today, there will be a moderate percentage of A blood type, but also many other blood types there, they will have shared a common agricultural background, eating dairy products and so forth. Lets say if they have O blood type, according to the blood type diet they should eat a particular type of diet, but in fact all of those Os, As and ABs all descended from people with a similar farming and dairy background. That recent experience, regardless of their blood type, is going to be more important to determine what kind of diet they should eat today.So pay attention to where your ancestors lived, as opposed to what their blood type is.