Do You Have Skinny Genes?

05 January 2016
Presented by .

With the New Year, there's often a resolution or two to make a new you. But what makes you, you? Given that we share over 99.9% of our genes with each other, there's a lot of variety in that 0.01%. Just look around you now - no two people are alike! Is it just your genes or is there something else at play? In this edition of The Naked Scientists, Graihagh Jackson goes in search of what makes a person, an individual beginning by asking why her brother got sixpack abs and she didn't...

In this episode

00:55 - What makes you, you?

Take a look around you, no two people are alike. Even within ourselves, we're always changing but just how much can we adapt?

What makes you, you?
with Professor Mike Tipton, University of Portsmouth

When you say the word "me", you probably feel pretty clear about what that Peas in a podmeans. But what actually makes you, you in a physical sense? And why are we so different? Mike Tipton put Graihagh Jackson's stamina to the test by repeatedly exposing her to cold water to show just how different we all are...

Mike - A friend of mine who was the last remaining human physiologist, I think, at one of the universities in the North of England, and biomolecular guy asked him what he did, and he said "human physiology".  And he said "my goodness, human physiology.  How do you deal with all that variability?" and, of course, it's in the acceptance that people vary and, in trying to find out what that source of variability is that you gain understanding into why some people survive in cold or heat, why some people even survive on intensive care, and some don't.

Graihagh - This is the drive for Dr Mike Tipton's research, at the University of Portsmouth, he's finding out why we vary so much. And believe it or not, it's not to curb my curiosity when it comes to why Charlie has abs...

Mike - We share much the same genetic material, but what parts of that genetic profile are activated and which aren't is one source of the variation and the other is people's experience.  So, how much time they've spent in different condition and how physiologically and psychologically adapted to those conditions they become.

Graihagh - You've designed some sort of horrific demonstration for me to partake in today.  Can you tell me a little bit more about what we're going to be doing?

GraihaghMike - Yes. Well probably the most dangerous response to an extreme environment that we know is the 'cold shocks response' to sudden exposure to cold water because generally you lose control of your ability to breath-hold.  That leads the aspiration of just the one and a half litres that you need to drown.  And so one of the things that we've been looking at are ways of trying to protect people, not only in terms of technology (clothing, lifejackets and things like that) but also physiologically against that response.  Now we know that humans can adapt to altitude, can adapt to heat but there's always been a bit more of a question mark over whether or not they can adapt to cold, and particularly cold water.  So what we'll try and do today is see if there's a very short protocol of repeated exposures to cold that can actually improve your chances of being able to control your breathing on exposure to cold water and, therefore, diminish the chance of drowning.

Graihagh - Mike mentions drowning here because when people fall into the water, they gasp and by gasping they inhale water - it's part of the fight or flight response, you need oxygen to do either - and whilst above ground this is okay, it's a good thing, in water, it's why drowning it's the third most common form of unintentional death worldwide. Other than to stop this gasp response, the demonstration aims to show how much we all vary (my heart rate reading will be different to others for instance) but also, how adaptable we all are. This is why Mike thinks he doesn't have to do the demo with me, although it's probably not the only reason...

Mike - No, I mean there's all kinds of reasons.  Some of which you've touched upon, but there are other reasons as well. One - somebody needs to be monitoring what's going on.  And, in fact, there is a long tradition in extreme environmental medicine and physiology that the people who research in it are normally their first subjects - you know they test themselves.  And so, I've done this, which is one of the reasons you're doing it now.

Graihagh - So we're going to look at how quickly I can adapt to these cold water environments by monitoring my heart rate and, also, how long I can hold my breath?

Mike - Yes, very simple

Graihagh -   How cold is this water going to be?

Mike - I think about 15 degrees.  So that's about the average sea water temperature around about this time of the year.

Graihagh - I was a little nervous to say the least.  Once wired up to the ECG, my heart rate had rocketed to 90 beats a minute - normally it's around 50.

Mike - So what we'll ask you to do here is we'll stitch the shower on.  We'll ask you to start a breath hold just before we switch it on, and then hold your breath as long as you can.  Then, we'll also have a little look at your heart rate ECG just over that one minute, and then we'll warm you up, wait 10 or 15 minutes to get you back to normal.  Then do the same thing again and look what happens over 5 one minute immersions.

Graihagh - It's quite cold.  I feel like I could maybe hold my breath.  How long's that been?

Mike - About 30 seconds... And that's it.

Graighagh - That's it!  Like it's no big deal.  Brain freeze and slightly shaky.

Mike - You've done excellent.  So we'll keep you there and we'll put the water to warm and that will warm you through.  Then you can come out and have a bit of a rest and we'll go again. Shall we put that straight round to warm?

Graihagh - Yes. [screams] That's not warm!

Mike - I timed your - depends where you want to mark the end of your breath hold - but if it's with the start of speaking, it was about 2 seconds.

Graihagh - Yes.  Well the initial shock I think I did one of those pwhh - sort of horsey noises.

Graihagh ScannerMike - Actually, do you know what you said (bleep).

Graihagh - Can't use that in the recording.

Mike - But actually, that's really common

Graihagh - Assured me that I was really normal in my poor language choices.  I did four more of those minute long immersion. Later, over a hot cup of coffee, Mike talked me through the results...

Mike - So what we've got is the ECG which was recording your heart, and we've got a respiratory trace as well so we can get the breath hold time.  If we look at the first one, of course, what we can see is that, unsurprisingly, you were quite excited about the prospect...

Graihagh - I'd go for nervous, not excited. 

Mike - Yes.  Well your heart rate was quite raised.  You managed a breath hold time of about two seconds on your first one, and we can see exactly where that finished here because there's quite a lot of movement on the ECG trace that equates the expletive that you offered us at that time, but anyway it's interesting.  So there's a big respiratory drive that's come from going under the cold shower that's prevented you from holding your breath. Interestingly, on the second one your heart rate was higher.  Of course, once you've done it once, you're just that little bit more anxious the second time and the response is greater.  So going through three, four, and five, your breath hold times went from sixteen on number three, to 44 seconds on number four, and 45 seconds on number 5.  Which suggest to me, that you'd almost reached the level at which you were not going to habituate any more.  Your heart rate response kind of supports that.  It tends to follow a different pattern in that it stays high and then suddenly drops.  So you were 125 on the first, 150 on the second, 65, 62, 56.  Now that, I mean 56 is a remarkably low heart rate so, congratulations on that but it does also tell us that you've probably habituated as much as you're going to do.  So that five immersions was enough to reduce that response.

Graihagh - What's going on for me to adapt to that environment, in my body?

Mike - Well we think the adaptation occurs somewhere central to the peripheral cold receptors. Because we see a difference in the profile of the heart rate habituation and the respiratory habituation, it's probably happening beyond that point as well.  The other think that kind of suggests that is that, if we do a full habituation to cold, we can reduce the cold shock response by about 50%.  We then ask people to come back 14 months later and it's still reduced by 25%.  So it's a fairly permanent alteration in the neurophysiological response to a peripheral cold response stimulus.

Graihagh - Because, interestingly enough, I felt much, much better by the fourth and fifth one.  It wasn't as uncomfortable and I felt much more relaxed actually.  So surely, psychology has something to, some role to play in this?

Mike - It definitely does.  In fact, when we look at the two variables we examined today - heart rate and ability to breath hold.  Well heart rate is, in normal circumstances, is not under very much conscious control but, of course, breath holding is.  You've got a drive coming from those skin receptors which you're trying to suppress, and so part of what's going on is you're getting better at suppressing that drive as well as the drive going down as well.  We know that there is a sort of psychophysiological component.  But also, you can sensitise people; they get a little but anxious.  So there is a well-known presenter who has come and been immersed with us, and I always start an immersion in cold water by counting down 5, as I did today and now, if I see this person on the street I only have to count down from 5 and I think is heart rate doubles.  So we've kind of sensitised him.  And so yes, absolutely, this is not just a physiological adaptation, it's an interwoven physiological and psychological adaptation. So, if we put this in the greater context, the ability for that adaptation is a combination of your genetic profile which determines other things like fitness, fatness, and also your experience of exposure to the environment. So everybody has the ability to adapt.  That adaptation is limited compared to what we can do intellectually and is also determined by a combination of the environmental exposure that you've had and the genetic basis of you as an individual.

12:53 - DNA decoded... with singing

What's the difference between DNA, genes and a chromosone? No, this isn't some terrible science joke...

DNA decoded... with singing
with Barbershop Quartet Bald Zone

There's quite a few things at play when it comes to what makes you, you: there's DNAthe environment, your genes, your lifestyle even... But how much do they all interact and is there a dominant force or factor in all this? To understand, Graihagh Jackson decided to meet the barbershop quartet, Bald Zone, to better understand the peculiarities of DNA...

Graihagh - So DNA: it's a molecule - a bunch of atoms stuck together and in the case of DNA, in the form the shape of a long, spiraling ladder. That's if you stretched it out - in real life, it's actually tightly wound up and sandwiched between structuring proteins to form a chromosome.

This recipe for life is in each and every one of our cells and a gene is just a section of the recipe - an instruction like 'peel the potatoes' or 'dice the onions.'

And just like those words can be broken down into individual letters, genes too are made up of a sequence of four letters or bases, which scientists call...

Singing

And A pairs with T, and G goes with C

A different sequence of bases would make a different gene, just like how a different sequence of letters would make up a different word!

They can be really long 'words' - over a million letters long or as short as 300 letters long...

Humans have roughly 20,000 thousand genes. And these genes code for certain proteins - you may have heard of haemoglobin - this is a protein found in red blood cells and helps to transport oxygen around the body...

These proteins mix together with other chemicals in the body to build things like eye colour, or freckles or indeed whether you're a tenor...

Singing

...or base...

Singing

Graihagh - Pretty cool huh? Thank you to the barbershop quartet, Bald Zone for helping me out with this one, here on the Naked Scientists. They were singing an old Jamaican folk song The Banana Boat Song - do you know how many genes you share with a banana? Go on, have a guess. It's 50% - you share half your genes with a banana. Pretty mind blowing stuff, eh?

15:55 - Why humans are so different

We share almost all of our genes yet, we are totally different. Even siblings are very different, so what determines your genetic recipe?

Why humans are so different
with Professor Hugh Montgomery, UCL

We share almost all of our genes with one and other yet, we're totally different. Ifcrowd you get a combination of your parents genes - what determines what traits you get from which parent? Professor Hugh Montgomery took Graihagh Jackson through her A, T, Gs and Cs...

Hugh - Well fairly straightforwardly you've got your genes.  You probably know roughly 20,000 genes is what you've got, and it's that common inheritance of 20,000 genes that are pretty much the same that makes you a human being - that's what determines your species.  But you inherit half of those genes from your mum and half of them from your dad and what determines the way you are is the combination of those genes that you inherited, the gene variants in them, and the environment that you expose them to.  And that's why you're different from your brother, or indeed from any human that's ever lived before or who will ever live in the future.

Graihagh - When you say gene variants - what do you mean?

Hugh - Well there are subtle variations in that sequence that means that those genes differ very slightly.  Now some of those variants don't do anything functional at all, but some of those little changes are in areas that regulate the way the gene is expressed - so you could imagine that as being a slightly twitchier brake or accelerator pedal in the bits that control the gene.  So those gene variants can make no difference or they can make quite big differences, and those variants come in different flavours.  There are big differences where you can have an extra bit of a chromosome tacked on the bottom end, or you could have a bit missing which is called deletion variance, or you can have copying errors where pretty much an entire block of a gene has been copied several times, so you end up with repeat sequences.  So lots of ways in which it can vary.  Not much of it's variable though.  You are very, very similar to other human beings in your genetics but you are very different in who you are.

Graihagh - This is quite a staggering thought - we share almost all of our genes with one and other yet we're totally different. So your environment must be a pretty important factor in shaping you, just how much though?

Hugh - The rest of its environment and, as a rough rule of thumb - and it is rough, you could say that roughly 30% of the variation in any particular trait, any particular way you are, will be down to the genes you've got and sometimes it's a lot more.  So, if you look for instance at how fat teenagers are - 13/14 year olds - oddly enough more than 70% of the variation in that is due to genes.  And that applies to everything - it applies to whether you drink alcohol, if so how much, how tall you'll grow, how fast you'll run.  So, if you think of the alcohol thing, there's strong genetic traits whether you choose to drink and, if so, how much but a very, very strong environmental signal.  So, if you're in a country where you cannot buy alcohol then you can't drink any, and it it's priced to a point where it's massively expensive, alcohol consumption will be low, and that's an environmental factor interacting with the genetics you've inherited that predisposes you to choosing to drink.

Graihagh - Hmm... My brother and I, we grew up together and experienced the same environmental pressures, so does that mean Charlie has a six pack gene?! Is there even such a thing? As it turns out, there are actually very few 'fitness genes' that we know of...

Hugh - If you don't know where to look it's a needle in a haystack.  There are probably another three or four for which there is solid evidence; there are good data to say its influential.

Graihagh - You discovered the first fitness genes - the ACE gene. I wonder whether you can just unpick what that is and, actually, how you discovered it, because you've already mentioned there's 20,000 genes.  How did you just identify that one gene as being really key in your fitness ability?

Hugh - Well I suppose it's probably fair to say we found that, to a degree, by chance.  There are many ways in which you can try to identify the relationship of one gene or gene variant with a physical trait.  We took what's known as a candidate gene approach.  So it's where you have a suspicion that a gene or a gene variant is doing something and then you look to see whether it is.  Now in this particular case, this gene called ACE which encodes something called angiotensin-converting enzyme - that's why is known as ACE, and we wanted to know whether this gene and its product Ace regulated heart growth in humans.

So I asked the Army if I could ultrasound scan the hearts of army recruits at the start of training and at end of 10 weeks of training.  If we could relate the size of their heart to the gene they carried.  So in principle exercising makes you heart grow stronger - it's like any muscle, if you exercise it, it will grow.  In this case, the recruits are all basically the same age and race and in those days the same sex as well - all men, and they were all undergoing exactly the same physical training, and they were eating the same food, drinking the same water.  So in this case, we controlled for the environment.  So they were all getting the same environmental drive for the heart to grow and, therefore, pretty much all of the difference in heart growth will be genetic.  So we have taken the environmental bit out and what we found was we were right.

Graihagh - Now, remember how Hugh talked about how genes variants and how genes express themselves differently? In the case of the ACE gene you could you could have few extra base pairs tacked on to the end, which they called the I variant;

Hugh - Or you could have missing, which is called deletion variance.

Graihagh - The deletion variant form of ACE is called simply called, D.

Because you get one gene from your mum, and one from your dad you can be DD, II or DI.

If you have the DD, you produce much more of this muscle making protein, ACE. The army folk grew bigger hearts but they actually worked harder too.

If you're II, you may work less hard, but as a result, you're much better at conserving your energy and thus, endurance sports...

Hugh - And what we found that people with two D versions of genes, hearts grew many, many tens of times more than the people with two insertion bits, the bits present where they had low expression of this ACE.  Now one of the obvious confounders of that would be to say, well yes, Hugh but that's rubbish isn't it, it's just that the DD people worked harder and their heart had to work harder to do the same exercise.  And we thought, well that's not true, but we'll look and see and it turned out that it was true.  That to get the same external workout on a bike, if you measure how much people were pedalling to get the same external workout, the poor old DDs were having to do a lot more mechanical work and their hearts were having to work a lot harder too.  Anyway, to cut a very long story short that told us that ACE was important with fitness, and what we found was that the I version of the gene tracks with endurance performance.  So, this is if you're wanting to do something that involves fatigue resistance or very long very long distance running, you want the I version, and if you want to build up strength or do a power sport like swimming or sprinting, then you want the D version.

Graihagh - What are you?

Hugh - Well I'm a DD.  I should put a caveat on this - this is a very personal view - I don't think it's a good idea to be genetically tested but, as it was back in the day, I did run mine for experimental reasons and I know that I'm a DD.  Now it fits with my sporting history; I was a strong swimmer, so all of that tracks well with that genotype.  The bit that doesn't is mountaineering.  Mountaineering is very strongly skewed towards IIs.  DDs - there aren't many amongst elite mountaineers.  Only about 5% of the elite mountaineers we've looked at are DD.  I'm not elite; I can certainly get up big mountains though, and I suppose the point about that is most things in life aren't down to just one gene variant - there are many gene variants.

Graihagh - I'm starting to think everything about my life might be slightly predetermined and I have no choice in where I'm going or what I'm doing.

Hugh - Well it's certainly true that part of it is.  I mean the part of you, you have not been able to regulate what colour you hair was unless you get a bottle and dye it.  You couldn't regulate how tall you chose to grow, you just grew didn't you?  You ate and you grew.  If I told you; if you really, really, really, really starve yourself to the point of ridiculous, you wouldn't end up a few inches shorter.  You might have had some control over it but beyond that you wouldn't.  So a lot of what you are; you just need to think of some of things like your behaviours as being like hair colour, they are strongly genetically influenced but you have some control over them.

25:05 - Reshaping your genetic destiny

If genes aren't the only factor in fitness, what other forces might be shaping who we are? Could we therefore control our genes?

Reshaping your genetic destiny
with Professor Tim Spector, Kings College London

If genes aren't the only factor in fitness, what other forces might be shaping who Nimmy and the twinswe are? Could we therefore control our genes? Quite possibly... Professor Tim Spector talks through the emerging field of epigenetics with Connie Orbach.

Tim - I thing genes are overrated and we have to remember that we have less genes than the worm.  So clearly, it's what you do with you genes rather than the number and the type of the genes that are important, because we like to think we are a bit more sophisticated than the average worm.  So my work has really shown that genes are overrated; there is no real such thing as genetic destiny and that we've evolved to be much more flexible than people think.

Connie - Overrated! That seems a little controversial.  Any everyone says how similar identical twins are.  I wanted to look a bit deeper into this so I thought I'd go to meet a pair that I know really well.  Meet my nieces, Florrie, Mabel and their mum, Nimmy Orbach...

Nimmy - it turns out Mae Mae's got the same mummy as you so you've to share, you do.  Is Mae Mae allowed a cuddle from mummy as well?

Florrie -   No!

Nimmy - They are completely two separate people.  Their reactions to, you know, a bump, bumping their head.  A reaction to the food in the moment.  They like completely different things, they make completely different choices.  They often want the same thing as one another in the way that siblings do.  You want what your brother's got, what your sister's got.  They're definitely twins but they're definitely, definitely two separate people.

Connie - And that's amazing because really, at this age, they've spent absolutely every, almost every second of their life together.

Nimmy - Pretty much.  I think they've been apart; there was one walk where they were taken separately on different walks and other than that they have literally been, you know, in the same house or, yes they're always together yet completely different.  They were completely different from the moment they were born and lots of the things that we could see as differences between them at the beginning that we kind of didn't want to associate with them at the beginning, have stuck a bit.  You know, the whining and the groaning and I won't tell you which one is more of a whiner than the other one in case she listens when she's older.  But one whined more than the other and she still does a little bit.  It's amazing that they can have had the same experience, the same upbringing, the same genetics, and be so completely, undeniably different.  Can't you Florrie?

Connie - Okay.  So it seems there is something in this, and much more than just my two year old nieces.  Tim has actually spent the last 23 years studying 10,000 pairs of identical and non-identical twins.

Tim - The last five or six years, I've turned my attention to why identical twins can very often be different.  When all of us look at identical twins we see amazing similarities but, when you scratch beneath the surface, we find that although there's a general tendency for things to go together.  When there's a key event like heart disease or Type 1 diabetes, the chances are when one twin has it, the other one actually won't have it.  So this goes against popular perception where they think, identical twins who are essentially clones with 100% of their genes identical in every cell of their body, end up having rather different lives.  Not only diseases, but also more likely than not if one is gay, the other is more likely to be straight.  If one has extreme political views, the other one may have different political views.  So sometimes it looks like this part of our makeup makes us much more flexible than we'd have believed.

Connie - You're saying some really quite fundamental differences if we're talking about diseases, which we expect to be quite genetic but also beliefs.  It's not just nature, it's not just nurture but there's something else going here.  What is that?

Tim - I think another big player here is epigenetics.  That is the way in which our genes are switched on and off by chemical signals, and these chemical signals vary in all of us and can be influenced themselves by genes, but also by our environments and by chance.  And one of the projects we've been looking at for the last five years is what differences between identical twins for any of these traits can be explained by differences in how their genes are epigenetically altered.  And it looks promising that some of these changes; the differences in identical twins can be explained by these epigenetic switches.  We don't yet know they're totally causal or whether they're just passengers at the moment.

Connie - Can you maybe give me an example.  Take me through what can happen throughout their life to end with very different consequences.

Tim - Often there was a story of a family trauma happened when they were young teenagers or kids, and they react differently to that trauma.  If there was a divorce, one would take comfort eating, the other would become anorectic and you'd then get a chain reaction after that because the two of them would, in effect, alter their genes because of that and in a way would always be different after that point.  Time after time, twin studies have shown that twins will react differently to the same environment, which is kind of weird, but it might be an evolutionary idea that to keep us more variable and keep us less predictable as a race and transfer, in a way, different genes on to the next group of people.  So that our predictability is perhaps being linked to our survival and the way we've escaped predators, and it might explain some our quirkiness in the human race.

Connie - When you mentioned epigenetics, we're talking about lifestyle and life events influence being back on your genes.  Is that something that you can pass on to the next generation?

Tim - You certainly can in animals.  Laboratory animals have shown that, for example, anxious experiences or stress can be passed on to the next generation even if that generation wasn't stressed, and there's epidemiological evidence that you can pass on some of these experiences on to your grandchildren.  But the data is great in humans, but I think there's an increasing awareness that this is a phenomenon that does occur in nature so that the offspring are perhaps better adapted to a different environment than the one the mother had, and what we don't yet know is how important this is humans.

Connie - So I guess Florrie and Mabel may only get more different as time goes on and they start to make their own life decisions.  Maybe the saying's right and 'variety really is spice of life.'

Nimmy - Where's Mabel gone?

Connie - Where's Mabel gone?

Nimmy - Hey Florrie, where's Mabel gone?

Graihagh - So Connie you're here with me now.  Your twin nieces are absolutely adorable by the way.  And that's really quite a staggering thought that what I'm doing now might affect my genes enough that my kids might feel those effects also.

Connie - I know it really changes what you think about just general everyday decisions.  You know so often you think, hey I can do whatever I want - I'm young - I can smoke some cigarettes, I can go out and drink but then when you actually think about what that might mean down the generations, maybe we're all going to just become really sensible and maybe a bit boring.

Graihagh -   Do you really think it's going to change how you view things and how you do things?  Perhaps you might encourage yourself to go on that run or not have that extra drink.  I mean often it's so hard to envisualise something that's so far away and so far in the future.  I mean for me anyway when I'm thinking about having children.

Connie - Yes.  I mean that's definitely true.  I think the situation we're in with climate change shows that as much as anything else.  Maybe I say I'm going to be more responsible, but probably, no, probably it's not going to happen.

33:36 - How do we evolve?

When it comes to flies, scientists can measure changes in DNA and in theory, we could use the same method to see if humans are evolving...

How do we evolve?
with Simon Collier and Dr Sam Lewis, University of Cambridge

Initially, what drew Graihagh Jackson to Cambridge University's fly lab was to Fruit flylearn about how scientists measure evolution - flies are often used to model humans when it comes to this sort of stuff - but when Graihagh arrived, she was completely overwhelmed by fly lab manager Simon Collier's office...

Simon - Yes.  We definitely have a fly theme.  I've worked with flies now for 20 - 25 years and, through the places I've been, I've accumulated a number of sort of fly souvenirs and my students like to give me little gifts of models flies or pictures of flies that they've drawn, and they sort of surround us right now.

Graihagh - They are great.  I really like them.  I feel like I've seen more of a fly than I've ever considered before.

Simon - Yes, and people don't really look closely at the these animals.  I mean we just have them buzzing around and mostly we think they're a nuisance, but they are really quite spectacular when you get up close and see what they're really made of. 

Graihagh - Ok, back to the science and to see what flies are really made of, Simon and I 'took flight' to the flylab...

Simon - So we're now standing inside the main flylab and we are surrounded by benches which have microscopes on and this is where fly people work.

Graihagh - So I don't know quite what I expected but I think when I came here I did actually expect more of a pet shop but actually you're right, its desk after desk, microscope after microscope.

Simon - Yes.  So out here is does just look like a lot of microscopes, but if we walk over here into one of the constant temperature rooms and we'll see it looks quite different.

Graihagh - Oh.  It's like a sauna in here.  It's nice and humid.  Actually, I'd say more steam room than sauna.

Simon - Yes. We keep this at high humidity and the temperature is about 25 degrees centigrade, which is a warm summer day.

Graihagh - Tropical and there are rows after rows of little test tubes filled with flies.

Simon - Yes.  So you can have a look.

Graihagh -  Oh they're all jumping around.

Graihagh - At the bottom of each tube you can see something that looks green and that's the food.  And the food is very simple; it's just cornmeal, sugar, and yeast - very cheap too, and if you leave the flies in that tube you can essentially just walk away.

Graihagh - It reminds me of a little essay I wrote when I was very young - I was about 7 years old - where I write about what the perfect pet is, and I write it's a snail because they don't need much looking after, and you can go on holiday and not have to worry about it and they don't need much food.  And afterwards, when you get bored - you can eat it.  And what strikes me about these is they are also very low maintenance although you probably don't want to eat them.

Simon - Well I'm sure we occasionally do by mistake, there are so many around.  Yes and they are low maintenance and I think, when you do the sums, we can accommodate, I believe, 60,000 of these tubes in these four rooms.

Graihagh - So if you can accommodate 60,000 tubes - there must be what 30, 40 flies in one of these tubes?

Simon - Yes.  Probably several hundred actually flies in each of these tubes, so you can do the maths and work out just how many flies we can have here...

Graihagh - I don't trust my maths!  Well as long as they're contained, although I do feel a bit itchy.  So these are all, obviously, various experiments going on.  What sort of things would they be looking for and doing with them?

Simon - A whole variety of things. But I mean the fruit fly is used as a standard model for biomedical research, and what I mean by that is we use the fly as a model so we can understand some general processes which apply to us as much as to the fruit fly

Graihagh - One fly fan is Sam Lewis - a postdoctoral researcher at Cambridge who works on evolution and genetics...

Sam - Well these are fruit flies which are one of the main model organisms that we use to study evolution.

Graihagh - So if you look at them down a microscope - what do you see?

Sam - Well one of the easiest things to see is the difference between males and females.  Females have a very white abdomen and the males are a bit slimmer and have a kind of black bum, basically.

Graihagh - And I assume when you are looking at them, you don't look at them down a microscope and see their DNA, so how do you go then from fly to looking at it's DNA?

Sam - Unfortunately for the fly, the first step is to grind them...

Graihagh - Brutal...

Sam - Then you can extract their DNA and then you can work out the work out the sequence of As, Cs, Gs, and Ts that make up a certain gene.

Graihagh - Why are flies so good to use as models when you come to look at genetics and evolution?

Sam - Well, it's the combination really of the amount that we know about most of the genes that they have, but also the amount that you can manipulate them to find out more about those genes.  So you can do a lot of different experiments putting them on different diets, or under different temperatures, and then you can look and see how that changes their genetic makeup and how that might then be triggering evolution.

Graihagh - How would you look at that?  How would you determine whether a fly has evolved or not?

Sam - There are two possible approaches - well a number of possible approaches, but two main ones are either comparing the genetic makeup of flies from different habitats and seeing if there are differences in the genes that might help them respond to those habitats.  Or you could take flies that you know the genetic makeup of at the beginning of experiments, split them into different regimes, so maybe one in a hot environment, one in a cold environment, and then evolve them under that selective regime for a number of generations, and then look at time points through the experiment to see how the genes are changing and, given that this is the only difference between them, you get a good idea of how they are responding to that change.

Graihagh - So say a fly's been put in a progressively, or generations of flies have been put in progressively warmer and warmer environments, how quickly would a fly evolve to be more comfortable, let say, in a warmer environment.  Is it within a few generations?

Sam - Usually it's slower than that but, given the precision that you can measure these things at, you can pick up changes that occur in dozens of generations.  I mean you can get really large effects by just looking at a few hundreds of generations which, obviously, would be a lot harder to do in humans, but in flies that's not all that long.

Graihagh - Yes.  I was going to say a dozen generations to see some changes and then say a few hundred for quite large changes - that seems remarkably fast.  Is that comparable in humans?

Sam - I don't think we really know without doing those kind of experiments.  It would be very difficult to say how quickly you could have seen it if you were looking a bit earlier.

Graihagh - I suppose the difficulty is, is that we have not been looking at people's genomes for the last dozen generations, let alone hundreds of generations.  We're just not that easy to study like the fruit fly and I suppose the other thing is, at least in a fruit fly, you can just expose it to a warmer environment or a colder environment, whereas, I'm not sure any human being would be happy with that sort of condition.  But there are so many things interacting and going on with humans that it's really hard to pinpoint what's changing where.

Sam - Yes, exactly, and one of the hardest things, I think, about inferring human evolution is kind of with humans and with moving populations and intermixing of different genes, it makes it a lot harder to say for certain when a change occurred, or even if that change is causing the effect that you think it is.

Graihagh - But I suppose that doesn't mean we're not evolving.  We just might not be able to tell how we're evolving.

Sam - Yes. There are some examples where there are kind of relatively clear changes that correlate with alterations in diet, for example, in humans.  So a gene called amylase breaks down starch and if you look at populations which have a high starch diet, they have more copies of the amylase gene, so they would have more amylase protein than populations with a low starch diet, that's being acted on by natural selection to allow humans to break down starch.

Graihagh - I'm thinking of potato farmers in Peru...

Sam - Yes.

Graihagh - High starch diet.  There is starch in potatoes - isn't there?

Sam - Yes.  I'm not sure which populations they looked at exactly.

Graihagh - Well probably my mum as well, and myself are big potato eaters so we probably have that starch gene as well.  So does that mean we are still evolving?

Sam - It's probably very difficult to say we are still evolving currently but it would be very surprising if we weren't, and we certainly have been up until very recently when we last looked.

Graihagh -  Last looked!  When did we last look?

Sam - The last few generations.

44:24 - Will mankind ever stop evolving?

To answer this question, we turn to horses. Why? Until recently, scientists thought they had reached a genetic limit when it came to speed

Will mankind ever stop evolving?
with Dr Jim Usherwood, the Royal Veterinary College

Will there ever be a point when we stop evolving? There might be a clue when Different horseswe look at horses. For years, scientists thought that race horses had reached their selection limit. They'd been bred and bred - the faster stud paired with the fastest mair - but trainers just couldn't make them any faster... However, some research published recently suggests that this may not be the case, as Jim Usherwood explained to Graihagh Jackson...

Jim - Okay, so we've been measuring race horse times for hundreds of years and over the last couple of decades, the very best horses have really been doing the same sort of times for the same sorts of distances and, we've been thinking of that, really they're not getting much better despite all the efforts in breeding and training that have been put in.

Graihagh - That's Dr Jim Usherwood from the Royal Veterinary College. There is a caveat here though. For thoroughbreds, there isn't a big enough gene pool or, you might say, not enough top dogs to mate with...

Jim - Here we're talking about thoroughbred racehorses and this is thoroughbred with a capital T which declares the breed, and the rules for being allowed to race in these races are fairly strict and constrain your breeding really quite strongly.

Graihagh - However, a publication earlier this year suggested that actually, we may have had it all wrong...

Jim - So there's this interesting, fairly recent study that shows that in elite short distances races, time is getting a bit better.  They agree that the winners of the elite races at medium/long distances aren't changing much but, in the shorter distances, they do appear to be getting better.

Graihagh - Why might this be the case?  Why might they be stopping short at the mid to long distances but getting faster at the short distances?

Jim - The authors of the Exeter report suggest that there could be a new influx of genes coming in from America.  Where I say new, they're still all thoroughbreds but, no, it can't be apparent from that kind of measurement whether it is genes or training.  Both could have accounted for a change there.

Graihagh - So horses haven't appeared, at least, to have reached their selection limit.  Do you think we'll ever get to a point where they will?

Jim - So, you can't infer from times whether it's selection limits or whether training is changing, of course.  Do I think that they might reach some genetic limit?  I just feel as though the limited genetic pool will probably constrain things to a certain extent.

Graihagh - Obviously with horses, we're choosing which horses to breed with which but, I suppose, when you're taking into account humans, that's a very different matter.  Would you ever consider humans to reach, perhaps, a selection limit?

Jim - When you're thinking about humans, of course, the genetic diversity is huge.  We don't have a Jockey Club or a Greyhound Board saying 'only these sorts of humans can race,' so we do have some diversity to work with.

Graihagh - Because there's so many of us and we're intermingling with each other all the time - there are a huge number of genes floating around - unlike the world of thoroughbred horses. But is there a limit on what we could achieve? Will we just continue to run the 100m faster and faster or will we just level off?

Jim - I think every time boldly write down what this limit is, the fun of athletics is that we tend to be wrong, and demonstrably so.  Before Usain Bolt, we are not saying those times are going to be broken.  Put it this way something as fundamental as why you get tired when we run isn't terribly well understood.  We can observe that we do, but why do we get so much more tired running than cycling?  And if you can't do something as simple as that then I doubt any guess at what estimates of top speed.

Graihagh - One thing that springs to my mind is - I'm thinking of all the sorts of drugs but also all the technical advances in say shoes or what have you - surely we'll just engineer stuff to meet our needs, to make us faster?

Jim - So that's one of the odd things about sport.  They go about putting some pretty arbitrary constraints on what you're allowed to change.  You could say shoes - you should be getting faster and faster shoes.  Yes, faster shoes have been invented, and then banned.  You can think of brush spikes, or you can think the Fosbury flop was allowed but somersaulting long jump isn't allowed.  So it depends on what the sports going to allow as to how much you're going to allow technology or technique to radically change things.

Graihagh - Would a simple solution just not to be 'hey, let's just have two different Olympic races.'  Let's have one with all the technology we can possibly get to see how fast we can get versus a more standard approach, I suppose what we do today.

Jim - And there you're touching on the ideas that motorsports got.  Do we allow technology to be part of the sport?  And sport doesn't have a consistent answer to that.  Cycling is an interesting one where the Tour de France put constraints on bike design to keep it fairly even, keep if fairly consistent across the years.  The Tour de France bikes are by no means the bicycles that we could design but it's losing some of the fun of the change you could make.  I'm torn between the two.  Should it just be a pure measurement of what humans can do - maybe...  I do quite technology actually.

Graihagh - I think in my eyes I think I'd quite like to change to see just what we could achieve if we were allowed to.

Jim - Are you interested in how humans can change? In our muscles and biomechanics can change, or are you interested in how well you can make a pole vaulting pole?  Of course, a better pole vaulting pole allows you to jump higher.  At some point, you don't want one that pings somebody so high that they get really, really hurt.  You could imagine weird prosthetics that would allow you to run really fast, but it means that you could really hurt yourself if you go round the corner the wrong way.  So there are bits where you want to keep people safe and you've got the question of - do you want to measure technology or humans?  Athletics tends to be focused on the humans.

50:46 - A different approach to getting fit

Getting fit can be a bore, but what if cardio was less about fitness and more about friendships?

A different approach to getting fit
with Paul Sinton-Hewitt, Founder of Parkrun

Parkrun is something that has taken the world by storm. It's a simple concept - Running9am on a Saturday, hundreds meet up for a 5 kilometre run. But as as founder of Parkrun, Paul Sinton-Hewitt explained to Graihagh Jackson, it's not really about the running...

Paul - I might not have said this ten years ago but where I stand today, looking at the Parkrun, then I realise that the running aspect of Parkrun is probably is one of the least important aspects of Parkrun.

Graihagh - Parkrun is something that has taken the world by storm. It's a simple concept - 9am on a Saturday, hundreds meet up for a 5 kilometre run. It started in Bushy Park, just outside of London, which is why you can hear parakeets galore in the background of this interview! But as a founder of Parkrun, Paul Sinton-Hewitt said, it's not really about the running...

Paul - What we do really, really well, and what is of vital importance is this community that supports people on the fringes of society to find to find friends, to find help, to be integrated into society and to improve their own wellbeing.

Graihagh -   Because what's really striking to me is that, obviously, you have this fantastic community going on where everyone - people on the fringes as you said get to meet other people - but also there is this fantastic benefit that hundreds of thousands of people are doing exercise every Saturday which they might not have otherwise done.

Paul - That's absolutely correct.  And it's not something that we really focussed on in the past but, right now, 2 million people are registered and a 1.4 million of those have participated - a hundred thousand people taking part every week.

Graihagh - You've sparked a bit of a global running 'revolution' then haven't you?

Paul - We call it a movement. 'Revolution' is probably a bit strong.  Everybody can run. Anyone who can walk can run and what parkrun does is it focusses, it's achievable for everybody and we just make it fun and, that way, I think we are changing people's behaviour.

Graihagh - What I'm going to be taking away from this is genetics can play a role in our abilities, there's no doubt about that, but also how training and lifestyle can significantly affect those ability but most importantly, our quality of life. You might die at the same age but actually, you're more likely to live those 80 odd years fit and healthy rather than as a bit aged and decrepit.

So, as the New Year dawns, whether it's at the gym, in the park or on the dance floor, I shall be keeping fit and having fun in the hope of a new me for 2016... Perhaps, even with a six pack to rival my brother Charlie's!

Charlie - Yes.  I don't see why not.

Graihagh - You're too nice!  I totally thought you were going to be like 'yeah right.'

Charlie - No. I think you could easily.

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