Nature Podcast 7 September 2006

Introduction

This is a transcript of the 7 September edition of the weekly Nature Podcast. Audio files for the current show and archive episodes can be accessed from the Nature Podcast index page (http://www.nature.com/nature/podcast), which also contains details on how to subscribe to the Nature Podcast for FREE, and has troubleshooting top-tips. Send us your feedback to mailto:podcast@nature.com

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Chris Smith: This week clear evidence of unintelligent design in the way the body deals with damage and cancer.

Gerard Evan: So I used to think that evolution had turned us into a well-oiled machine but now I realise we're just a load of garbage that's cobbled together that works just about well enough.

Chris Smith: More from Gerard Evans shortly. Also how the ancient carbon locked away in permafrosts is now coming back to haunt us as those permafrosts melt.

Katey Walter: We have discovered hot spots of methane bubbling where the bubbles of the methane have radio-carbon ages tens of thousands of years old, even though they were made by bacteria only yesterday.

Chris Smith: We'll also be hearing how volcanoes heat themselves up, which could trigger an eruption.

Jon Blundy: Decompression crystallisation, as we call it, is capable of heating up magma and triggering eruptions without the need to invoke some foreign source of heat.

Chris Smith: And how chemists are catalysing the process of making just left- or right-handed drugs.

Amir Hoveyda: If you're a chemist working in the area of medicine and you want to make molecules and test them you will be able to make those molecules a lot more quickly.

Chris Smith: That's all in this week's Nature Podcast. Hello, I'm Chris Smith. First up this week, are we all victims of unintelligent design? Well, that's the view of Gerard Evan who's used transgenic mice to investigate the workings of the anti-cancer gene p53 which stops cells with damaged DNA from dividing. By temporarily switching this gene off in mice when they're exposed to a cancer-causing dose of radiation he's found that it's possible to abolish the symptoms of radiation sickness but without affecting the likelihood of developing tumours. This of course could have profound implications for the way we deliver chemotherapy to human patients. Nature advance online publication 6 September 2006

Gerard Evan: For a long time we've known that the body has many intrinsic mechanisms that suppress the emergence of cancers, and these mechanisms are called tumour-suppressor mechanisms, and one of the most important is a protein called p53. Now, p53 is known to not only suppress cancer but also to get rid of cells that have encountered DNA damage, and for a very long time it's been assumed that the way that p53 responds to DNA damage is also the way that it gets rid of cancer cells. And I think what we've done is for the first time uncover evidence that maybe the DNA damage response and the ability of p53 to suppress tumours are not necessarily the same.

Chris Smith: So what have you actually done to try and work out what role p53 is playing in this process?

Gerard Evan: So what we did was we've got a new kind of model where we modified the p53 gene in a mouse so that actually we put a switch on it. So we can take these mice and flick p53 either into the functional or non-functional states reversibly. And then we can ask questions about, well, let's say this animal gets exposed to radiation – which we know is going to cause cancer – does it need to have p53 functional at the time of the radiation exposure in order for p53 to suppress the cancers? So now what we do is we take the animal, we expose it to a low level of radiation, which eventually will give the animal cancer. Now, if we have p53 functional at the time we expose the animal to radiation the animal gets radiation sickness. And then we say, well, let's put p53 back into the off state, has the death of all those billions of cells – which cause the animal some sickness – has it killed off all the potential tumour cells that the radiation would otherwise have caused? And the answer, amazingly, was, no, not at all. So it seems that all of that sickness you get from being exposed to radiation or chemotherapeutic drugs if you're a cancer patient doesn't seem to protect you from the cancers that those damaging agents would have caused.

Chris Smith: So what's actually going on?

Gerard Evan: Well, it turns out that when we do the reverse experiment, which is we don't have p53 functional at the time of radiation, of course the animals don't get sick because they're protected. Now what we do is we assume that they have got lots of little potential baby tumours in them, and now a bit later on we restore p53, but because there's no more damage – because it's all been mended – the animal doesn't get sick, but it turns out it still is protected from tumours.

Chris Smith: So does this mean if you've got someone who's an oncology patient, they have some kind of tumour, and you want to deal with them, that temporarily and paradoxically switching off their p53 for a little while could actually save them from some of the nasty effects of chemotherapy?

Gerard Evan: I think that's right. So actually suppressing p53 function in the patient's normal tissues certainly won't prevent you from treating the tumour because the tumour didn't have any p53 to start with, but it may allow you to use higher doses of radiation without the terrible side effects. And I suspect that what we've got now is we've just got a typical example of unintelligent design where an ancient piece of machinery has been co-opted into tumour suppression, and for that reason our DNA-damage response and our tumour-suppressor response are both conduited through the same engine, through p53. And I think the important point is it doesn't need to be that way, it's just what we've been stuck with by evolution, and possibly by intervention with drugs we can improve on what nature has handed down to us.

Chris Smith: University of California San Francisco's Gerard Evan, who's found that temporarily switching off p53 can prevent the pathological response to radiation but without affecting the ultimate chances of developing tumours. Now as the world warms up permafrosts are beginning to melt which is allowing bacteria to turn carbon-rich material laid down over 30,000 years ago into the greenhouse gas methane. But how much gas is being produced? Well, it's very difficult to quantify because most of it bubbles out from so called thaw lakes. But now Katey Walter from the University of Alaska Fairbanks has used bubble traps to measure how much methane is emerging, and it's enough to increase the methane contribution from northern wetlands by up to 63%. Nature 443, 71–75 (7 September 2006)

Katey Walter: This work is all about quantifying a new source of atmospheric methane which was previously not recognised as a large and significant source, and that is bubbling from thaw lakes, lakes where the permafrost is melting and the lakes continue to expand as they melt into that permafrost, that's where they get the name thaw lakes.

Chris Smith: So how have people tried to measure this in the past, or haven't they?

Katey Walter: In the past scientists have measured methane emissions from lakes in two ways, they measure the diffusive emission where methane moves along a concentration gradient, from the sediments into the atmosphere, and they've done that by just measuring the concentration of methane in the surface water of the lakes. Another source of methane from lakes is bubbling, and that's a much more difficult source of methane to quantify because bubbling is very rare both in space and time.

Chris Smith: So what have you done to get these accurate quantitations of them?

Katey Walter: We have the excellent opportunity in Siberia to study bubbling because when the ice forms on the lakes in Autumn it's like putting a piece of Saran Wrap across the surface of the lakes, it traps the bubbles in place as they wobble to the surface and then they freeze into place in the ice. And we can walk across the ice and map out the distribution of point sources and hot spots.

Chris Smith: So you walk out on the ice, you can see where the bubbles are coming up. But then how do you physically work out how much gas is there?

Katey Walter: We've constructed bubble traps out of greenhouse plastic and copper wire and we place those either under the ice or in the summer when there is no ice we just place them floating under the water surface and each trap captures the bubbles that come up continuously. And so we would go out every day and measure the volume of bubbles that had collected.

Chris Smith: So in the grand scheme of things how much methane is this actually contributing to the global environment?

Katey Walter: Well, scaling up, the type of Siberian lake that we were studying, we estimate that methane emissions from these lakes is about 3.8 teragrams per year. Now, these lakes are only a portion of the northern lakes in general so if bubbling is something that happens everywhere then this could be an even much larger phenomenon than just the scope of our Siberia work. And now we see that just adding this small portion of Siberian lakes to the northern wetland emission estimate it increases it by up to 63%, ten to 63%.

Chris Smith: So what are the implications if you add this to the global warming equation, then?

Katey Walter: This is a new positive feedback to global warming. Methane is a very strong greenhouse gas and so as methane is being produced it is trapped in the atmosphere, increasing atmospheric warming which then enhances the thaw and the expansion of these lakes further. So today there are still about 500 gigatons of carbon remaining in this unique type of Siberian permafrost and it's projected that during the next century the majority of that will degrade and that can release tens of thousands of teragrams more carbon into the atmosphere.

Chris Smith: So should this provoke a rethink of what we think is actually likely to happen in terms of global warming in the future, then?

Katey Walter: Well, one component of the general circulation models that is missing is permafrost degradation, and especially with regards to the large pools of carbon that are stored in permafrost. That carbon content is still poorly known let alone these positive feedbacks to climate change that can happen from permafrost degradation. So yes, we do have a lot of rethinking and incorporation of these new sources.

Chris Smith: Katey Walter, and as Katey points out, methane being a potent greenhouse gas fuels its own production by accelerating the process of global warming. She estimates that between 1974 and the year 2000 the amount of methane produced by expanding thaw lakes may have increased by almost 60%. Nature's podcast bringing the world of Nature to life. Coming up shortly chiral catalysts that can selectively produce just right- or left-handed molecules, how to smooth over turbulence in pipework, and the Shuttle launch that didn't take place. First though, volcanoes. Here's Bristol University's Jon Blundy, who's found a clever way to get a glimpse atthe inside of an active volcano to find out what happens to magma when the pressure's off. Nature 443, 76–80 (7 September 2006)

Jon Blundy: The paper really is the result of about 15 years of research I've been doing with colleagues in the US and at Bristol on some rocks from two currently erupting andesite volcanoes, one in Mount Saint Helens, and the other is Shiveluch volcano which is in the Kamchatka volcanic arc in far eastern Siberia. What we found rather remarkably is that as the magmas that fuel these volcanoes rise up beneath the volcanoes they crystallise in response not to cooling but to decompression, so a change in pressure causes them to crystallise. And as a result the crystals are forming in these magmas not because the temperature is going down but because the pressure is going down. And a curious side effect of this is that as the magmas crystallise they actually get hotter because the process of crystallisation releases latent heat of crystallisation and that causes the magmas to warm up. And although that's an effect that had been anticipated from simple thermodynamic considerations for many years this is the first proof that this is actually going on beneath these two active volcanoes.

Chris Smith: How did you actually prove that, because clearly you can't get inside a volcano to see it happening?

Jon Blundy: Well, that's one of the big challenges for the geologist, to try to track temperature variations in magma that is rising up beneath an active volcano several kilometres beneath the surface is extremely difficult. What we've done is we've looked at some little trapped globules of frozen liquid, they're now glass but they were once a silicate liquid, and these little globules are trapped in crystals, and the little globules are formed as the crystals grow and they can equilibrate and they can exchange chemical components with the surrounding liquid as the magma moves upwards. And they can do that for some period of the magma's ascent, and then eventually they become sealed off. Now, from the composition of that liquid – which we analyse with a variety of microprobe techniques – and the composition of the crystal just next to that little globule of liquid we can actually calculate the pressure at which the trapping occurred and we can also calculate the temperature. And when we piece together the evidence from these two volcanoes we see that the temperature increases by about 100 degrees.

Chris Smith: Now, I know you said that this had been predicted but not proven, and now you've obviously got the evidence for exactly how it can happen, but is it actually changing our view of how volcanoes in general actually work?

Jon Blundy: It is really because one of the interesting things that you see at many explosive volcanoes is evidence from the crystals they contain that shortly before they were erupted they were heated, and that's led to a quite long-lived paradigm that the trigger for an explosive eruption is the injection of a much hotter, less silica-rich magma into the system, and that's the trigger for the eruption. What we've shown is that the simple process of magma rising beneath a volcano and crystallising can release heat of about the observed temperature rise to trigger volcanic eruptions. So to an extent we've shown that the process of decompression crystallisation as we call it is capable of heating up magma, mobilising it, and triggering eruptions, without the need to invoke some foreign source of heat, if you like, some additional hot magma injecting into the system.

Chris Smith: Bristol's Jon Blundy describing how as magma ascends beneath the volcano it decompresses and crystallises, and that crystallisation produces heat that can then trigger further eruptions. Now, from volcanoes to handedness, not of people, but of molecules. Just like us the sugars and proteins used in our cells can exist in right- and left-handed forms which are mirror images of each other, or enantiomers. Now, the same goes for drugs, but in the context of drugs only one of the two forms might be active, which means that a chemical reaction producing both forms will only have an effective yield of 50%. Now Amir Hoveyda and his colleagues have produced a small molecule which works as a highly efficient chiral catalyst and produces a molecule with the right-handedness in a ratio of 98 to 2. Nature 443, 67–70 (7 September 2006) , Nature 443, 40–41 (7 September 2006)

Amir Hoveyda: The catalyst is the molecule that's almost a magical molecule that allows you to cause a transformation, a chemical reaction to occur that would otherwise not occur. A chiral catalyst is a catalyst that generates molecules that are handed. Now, handedness is extremely important in nature, one of the attributes or characteristics of some molecules is that they are handed, just like our two hands, our left hand and our right hand they are not super-imposable, they are mirror images of one another, and in nature molecules that are mirror images of one another can be very different. So this catalyst generates molecules that are not super-imposable on their mirror image and it generates only one of the hands, selects with very high selectivity. So some of the most important drugs, pharmaceuticals, are chiral, are handed, so our body is like a glove where one molecule will fit in and one hand will fit in and the other hand will not.

Chris Smith: What sort of molecules will your catalyst affect the production of?

Amir Hoveyda: A range of organic molecules anywhere between from anti-cancer agents, anti-AIDS agents, any diabetes compounds. So basically it is the catalyst that will allow our chemists to significantly shorten the number of hours that they will spend making molecules, so a molecule may become much less expensive if it's being marketed as a drug, the number of days that chemists will have to spend to make molecules will be reduced, or if you are a chemist working in the area of medicine and you want to make molecules and test them you will be able to make those molecules a lot more quickly.

Chris Smith: How did you come up with the design for the catalyst in the first place? So that you could do that?

Amir Hoveyda: This is a very good question, so now the word design is something that can be much debated. We have worked for a number of years on chiral catalysts that are made out of amino acids so we knew that that could be a direction we could go to address that need which is developing a sialylation catalyst. Also the environment, two of our colleagues here, one is Ross Kelly, the other one is Scott Miller, one has shown that hydrogen bonding is a very important component of catalysis, and the other one, Scott Miller, has shown that a class of compounds called imidazoles can be very important in catalysis. So basically the right environment, a need, and screening. So once we knew peptides could be the answer and we knew hydrogen bonding could be important we basically began to screen a small number of candidates and fortunately one of those candidates ended up being a very exciting hit.

Chris Smith: If you could shrink yourself down to the size of the catalyst and take a sort of bird's eye look at it what would it actually look like?

Amir Hoveyda: If I were a molecule and this catalyst was approaching me I wouldn't think it is a catalyst because most catalysts are much bigger. It is a heterocycle that is called imidazole, it's a ring of five atoms, two of them are nitrogen, then it's attached to a common amino acid which is called isoleucine, it's commercially available, and then it is capped by a simple amine. So it is extremely simple, I mean, it is a very common building block in organic chemistry, in chemistry, and we make these catalysts by three very trivial steps from commercially available compounds, compounds that you can buy from any vendor that sells chemicals.

Chris Smith: Amir Hoveyda from Boston College in the US explaining how he's developed the first example of a chiral catalyst that can produce only molecules with the right sort of handedness. This is the Nature Podcast from the 7th of September edition of Nature with me, Chris Smith. If you would like to drop us a line with any feedback about this programme we'd love to hear from you. Please write to mailto:podcast@nature.com. Now, what happens when liquids flow along a pipe? Well, normally a fluid establishes what is known as a laminar flow, with the liquid at the centre of the tube moving the fastest, and the liquid next to the wall of the tube moving more slowly. But if the pipe has a rough surface or if the fluid starts to move too quickly the flow becomes disorganised and turbulent. The accepted wisdom was that once the flow has become turbulent it remains that way, but now, Björn Hof from the UK's Manchester University has found that it's just not true and that a better understanding of the physics at work in a pipe might lead to better ways to solve the problem and keep things moving more smoothly. Nature 443, 59–62 (7 September 2006) , Nature 443, 36–37 (7 September 2006)

Björn Hof: The general assumption up to now was that once the flow in a pipe has become turbulent it will remain turbulent for all time. However, what we found now is that this is not the case, so our experiment finds that turbulence will decay after a certain time, and this time actually increases very rapidly with the flow rate.

Chris Smith: How were you actually doing this? Did you have a giant pipe in the laboratory to do the measurements with?

Björn Hof: Well, we actually build the new pipe just for this purpose, and in order to make this pipe very long – I mean, all labs have a certain size limitation and what we had to play with was 30 metres – but what you can do of course is to make the diameter smaller and smaller, and what is important for these experiments is the length in terms of diameter and so on, what we achieved now is a pipe which is 7,500 diameters long and that is, about ten times longer than most of the existing pipe used for such experiments.

Chris Smith: So how does the experiment actually work?

Björn Hof: What we do is initially we create a turbulent region in the pipe somewhere close to the entrance stage and then the turbulent region will travel down the pipe at the mean velocity of the flow and we can then observe at the end of the pipe if the flow is still turbulent or if it has gone back to the laminar.

Chris Smith: And what are the implications of what you found?

Björn Hof: We give this example in our paper of a garden hose with a flow rate of one litre a minute, which is a fairly small flow rate. In this example flow is typically the turbulent and if you now, from our findings, tried to extrapolate how long it will take for this turbulence to decay then you come up with a number of five years. So at these flow rates, although they are relatively small, you're already beyond any practical applications.

Chris Smith: With that in mind, though, are there any other areas in which this might be applied where it may have direct relevance?

Björn Hof: One of the essential points is that the turbulent state and the smooth laminar state are still dynamically connected and therefore there ought to be a way of by perturbing this turbulence slightly, if you're able to kick it in the right direction, to speed up this re-laminarisation process. So if only you knew how to influence this turbulence in the right way then it should be possible to speed the process up considerably in an exponential fashion and then you could actually come up with some low-cost control mechanisms for these turbulent flows.

Chris Smith: So it's not just a pipe dream. You can get rid of turbulence after all. That was Björn Hof. Now, finally this week, to the launch of the Space Shuttle Atlantis, originally scheduled to take place on August 27th, Nature's Geoff Brumfield went down there to watch it happen, but unfortunately things didn't quite go according to plan.

Geoff Brumfield: Okay, here's the deal, I convinced the Podcast folks to fly me down to Florida and cover the Shuttle launch. You see there are these great beaches near Cape Canaveral and I had a plan, go there, file a quick snippet from the launch, and spend the rest of my time playing in the surf, all on the Podcast dime. It was the perfect crime, until... rain, lots of it, and plenty of lightning too, which led to this.[unidentified male speaker]Good afternoon everyone, this is our briefing on the postponement of launch STS115 with Atlantis. Here to talk about the circumstances surrounding the postponement is LeRoy Cain, the Launch Integration Manager for the...

Geoff Brumfield: This is not good. As it turns out the launch pad was struck by lightning during the storm. The Shuttle Programme Manager, LeRoy Cain, lays out the situation as clearly as possible.

LeRoy Cain: We have one indication on one of the ground systems on vent arm, the ET vent arm, and... but we don't know yet whether it's a real indication or instrumentation. We also have an indication on the flight vehicle, on the orbiter, an indication on one of the essential 1BC bus that is showing a slightly out of... above a limit. But again we... it's a... it was an 80 millisecond data sample and it's not enough information to go on.

Geoff Brumfield: Now, your guess is as good as mine what he's talking about. I'm pretty sure I heard the word, essential, in there somewhere. Anyway, they want to take a few days and check things out, so they're calling the launch off, and while we're waiting this tropical storm, named Ernesto, comes straight for Florida, before you can say, lift off, we're in another press conference.[unidentified male speaker]Good morning everyone, and welcome to our briefing on the status of STS115. Here to talk about the circumstances relative to Ernesto is LeRoy Cain, the Launch Integration Manager...

Geoff Brumfield: Ernesto's bearing down on us, and Shuttle managers have made a decision to move Atlantis off the pad. That means no launch, at least while I'm here, LeRoy Cain sums up the mood in the room.

LeRoy Cain: We are here to go launch the Space Shuttle, I mean, that is why all of our friends and colleagues have travelled here for these final preparations and reviews, and that's what we're about. So, yes, there's a disappointment. I'm disappointed.

Geoff Brumfield: Disappointed? I'm screwed! I've got nothing. I'm getting a little desperate, I need to give the Podcast something from this trip. I make a last-ditch appeal to NASA spokesman, Allard Beutel. Alan, I want you to do your best impersonation of a Shuttle launch for us right now.

Allard Beutel: Yeah, it makes a lot of noise... yes.

Geoff Brumfield: Are you sure you don't...

Allard Beutel: Yes, I appreciate the invitation...

Geoff Brumfield: Oh, oh, no, no, no. I, I'm willing to pay you money. They're really going to kill me, because they've spent a lot of money on this. Come on, just a little, just a little whoosh.

Allard Beutel: I'll let, I'll let the Kennedy Space Centre professionals who do this for a living give you, three, two, one, we have lift off.

Geoff Brumfield: Well, I guess that's all the Podcast is going to get. And since there's a day or so before the storm actually hits I'm headed to the beach. From Cocoa Beach... I mean, Cape Canaveral, I'm Geoff Brumfield.

Chris Smith: And I can thoroughly recommend Cocoa Beach, although I should warn you, Geoff, that in the wake of severe storms pieces of Portuguese Man of War jellyfish often end up in the surf. Unfortunately no one told me that when I took a dip there after a hurricane. Well, on that painful note that's it for this week, and thanks very much for listening, but do join me next time, when I shall be dipping a toe into the early universe. In the meantime, this week's edition of the Naked Scientist will be reporting daily from the BA Festival of Science in Norwich, UK, you can catch those reports via the Naked Scientist Podcast at http://www.thenakedscientists.com. This week's Nature Podcast was produced by Derek Thorne and Anna Lacey, and I'm Chris Smith. Until next time, goodbye.AdvertisementThe Nature Podcast is sponsored by Bio-Rad, at the centre of scientific discovery for over 50 years, and on the web at http://www.discover.biorad.com.