Nature Podcast 23 November 2006

Introduction

This is a transcript of the 23 November 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, researchers have found that some people can taste words that are on the tip of their tongues before they can even say them

Julia Simner: I show them a picture of a platypus and they say oh, that's... um, I know what it is and I'm tasting Dutch chocolate, but I don't quite know why, so what we're able to show is the taste will flood their mouth even before they're able to name the word.

Chris Smith: And we'll be hearing more from Julia Simner very shortly. There's also hope for improved therapies for colon cancer, a scientist isolate a stem cell that causes the tumours to recur.

John Dick: I liken to having a weed in your back garden, you can keep cutting the leaves off of that weed and the weed is going to keep re-growing, but if you actually go in and cut the taproot the leaves will eventually wither away, and what we need to understand is what are the cells that are at the root of cancer?

Chris Smith: And just when we thought we'd finished the Human Genome Project...

John Dick: We found huge chunks of DNA missing from every individual that we studied.

Chris Smith: Someone comes along and throws a huge spanner in the helix. And then there's this.

Rebecca Forth: Keep it going now, keep it going, keep it driving, that's excellent, keep it driving...

Chris Smith: No, its not a recording from the Nature press office, in fact it was Nature's Mike Hopkin finding out whether he's up to the job of scaling Everest. We'll be finding out how he got on just as soon as he's finished being resuscitated. Hello, I'm Chris Smith, welcome to this week's Nature Podcast. First up Julia Simner and the subject of um, what's the word, um, synaesthesia, that's it. She's been looking at what happens when people with synaesthesia, who normally experience a taste sensation when they hear certain words, end up in a tip of the tongue situation, in other words, doing what I just did and not being able to remember the word. Bizarely they can't actually remember the word they want but they can still taste it. Nature 444, 438 (23 November 2006)

Julia Simner: In a nutshell our study looked at a group of rare individuals who experience a type of merging of the senses, we show that for these individuals merely thinking very hard about something is enough to trigger a perceptual sensation of taste in the mouth and that different tastes are experienced depending on what they're thinking about.

Chris Smith: So how did you actually do the study?

Julia Simner: The study is based on a technique which has been used a lot before and it's quite a clever technique, I like it quite a lot. What we had to do was place our synaesthete in a tip of tongue state. Now tip of tongue is the common sensation of knowing a word but not being able to say it so, for example, if I showed you a picture of a platypus you might say "oh, I know what that is, it's a um, um... oh I know what it is, it's a platypus", but at that moment when you're saying um, you're in top of tongue state, you've basically retrieved the meaning of the word but you just don't know how to say it. So this is really the technique we use for our synaesthete, we show them picutres of unusual objects, a platypus, artichoke, gazebo, words that they don't use in everyday languare and we just ask them to name what was on the picture and in all cases they recognise a platypus, they know exactly what it is but these words are very good at placing somebody in a tip of tongue state.

Chris Smith: And then how did you assess their synaesthetic experiences at the same time as they were experiencing the tip of the tongue situation?

Julia Simner: When they're in a tip of tongue state, when they're umming about the word, we say okay, you don't know what this word is but do you know what it tastes of? And so the synaesthetes tends to say something like, you know, I show them a picture of the platypus and they say oh, that's um, um, I know what it is and I'm tasting Dutch chocolate but I don't quite know why. So what we're able to show is that when they're in a tip of tongue state the taste will flood their mouth even before they're able to name the word.

Chris Smith: So what does that tell you about where in the processing order the experience of synaesthesia comes in the stream of conciousness?

Julia Simner: Well our aim really was to ask one specific question: if words trigger taste is the taste triggered by the word meaning or is it triggered by the sound of the word and the spelling of the word? And what the tip of tongue experiment is able to show us is that those tastes are triggered by word meaning because when you're in tip of tongue state you simply don't know the sound of the word, you don't know the spelling of the word, you don't know anything about it at all. The only thing you know is a word meaning and so what we can do now is we can say that, in our model of synaesthesia taste centres are linked to word meanings, not to the part of the brain that processes the sound of words.

Chris Smith: And if you then present that person with some Dutch chocolate do they then turn around and say ah, platypus?

Julia Simner: Well it's really interesting, actually, whether it's two directions or not. So in the vast majority of cases synaesthesia seems to be unidirectional, that means it only works in one direction. Interestingly there are two amendments to make to that. The first is that every now and then we do find a synaesthete who's bio-directional, so I do know one lady in America, she's one of our participants, and for her not only can she tell us that William tastes of potato but she can also tell us that potato word is William. The second thing to qualify this study is that some recent studies seem to suggest that, even for those synaesthetes that have it in only one direction, consciously, it's possible that there might be, sort of, a subconcious bio-directional link that, even though they can't tell you what a potato word might be, that when they taste potato or they think of potato they are actually accesing the accociated word, even though they can't bring it to a conscious level.

Chris Smith: Edinburgh University's Julia Simner who's found that synaesthetes, when something is on the tips of their tongues, can still taste the word they want, even though they can't remenber it, showing that it's actually the meaning of the word that triggers their synaesthesia rather than the sound. And now to colon cancer which is one of the Western worlds leading cuases of death. But there's every reason to be optimistic now because in two independent papers in this weeks Nature, scientists have described how they've uncovered a chemical marker called CD133 which singles out tumour cells that have stem-cell-like properties and this is very important because it's these stem cells that probably cause the disease to spread and recur. Here's Toronto University's John Dick. Nature advance online publication 19 November 2006; Nature advance online publication 19 November 2006

John Dick: Work in the leukaemia's and breast cancer and brain cancer had suggested that, in fact, certain cancers seem to be hierarchically organised, there are only rare cells in the cancer that actually have this unique property of keeping that cancer going and that means that those cells must have this property that we call self renewal which is a property that's aligned with stem cells. Colon cancer, of course, represents one of the major human cancers and it had not been determined whether or not the same principle actually holds true for this kind of a cancer and it's critically important because the reality is that, despite the therapies that we have today, still a great number of people who have colon cancer relapse which means that our therapies are not completely effective.

Chris Smith: So what sort of strategies are you coming up with to try and surmount the block?

Paul Riley: Well, what we've been doing, is we've been looking at certain factors and proteins, really in their role in heart development and, in doing that, we've found a protein that seems to also stimulate adult cells as well.

Chris Smith: So what have you done to try to work out exactly what is going on in colon cancer and to show that, in fact, what we've found for breast and our other tumours is, in fact, holding true in colon cancer too?

John Dick: The fundamental way to test which cells have the capability to make a cancer was take human colon cancer cells, take immune deficient animals that don't recognise the human cells as being foreign, we transplanted different doses of cells and basically asked how many cells do you need to give to get a tumour and what we've discovered was that only one in 60,000 cells actually has the ability to initiate tumour growth.

Chris Smith: And what sorts of cells are they? They're obviously some kind of very potent stem cell in there that's driving this but what are the other cells doing if they're not actually proliferating the tumour?

John Dick: Well the cells could be proliferating but they don't have the capacity to initiate the graft. And so we've focussed on this marker called CD133 which had been predicted from other tumour systems and other stem-cells systems to be an immature cell marker, and so we looked at colon cells in the colon tumour and realised that is was expressed but it was variably expressed. Some samples only had 1%, some samples had 20%. So we fractionated those cells and we collected two pots of cells, one which would be the bulk of the tumour, which were 133 negative and then a smaller fraction which were there 133 positives. We took those to our assay system, implanted both of them and asked which one's gave tumours and what we found was that only the 133 positive gave tumours, we never got tumours from the 133 negative cells.

Chris Smith: Our second paper in Nature this week, by Ruggero De Maria in Italy, finds largely the same result, Rigero you've actually extended these findings, though, in vitro?

Ruggero De Maria: Yes, we're able to get a population of pro-genitals and stem cells, CD133 positive, growing almost forever so we have cells growing for almost two years now in culture and they are able to reproduce the same tumour at least histilogically very similar to the tumour from the patients from which we derived these cells.

Chris Smith: And in the same way as John Dick has just described, by transplanting those cells into animals, you were able to recapitulate the tumours in vivo too?

Ruggero De Maria: Yes, the tumours are very similar to the tumour of the patients, like in terms of a cytokeratin expression CDX2 which is the normal marker used by pathologists for diagnostic procedures.

Chris Smith: So now that you're in this position to propagate these stem cells, what are the implications of being able to have this technology and have this cell marker so you can identify these stem cells?

Ruggero De Maria: It's very important because you can characterise these cells extensively. So we are doing a lot of analysis for different protein levels and RNA levels, and microRNA levels so we can get a lot of information for finding some way that we can target to cure the tumours. We're also developing a stem cell bank that can be used for pre-clinical studies because the majority of pre-clinical studies are done with regular cell lines and I think that these cells are not very representative of the real disease.

Chris Smith: And John do you share that view and also what will you be doing to take this forward now you've identified this stem cell?

John Dick: Yeah, I think our focus will be to try to purify these cells to even higher extent. Our analysis had shown that while every cancer-initiating cell was 133 positive not every 133 positive cell is a cancer initiating cell. In fact, only one in 250 of them are and so we certainly have a way to go to try to achieve higher purity.

Chris Smith: But from a patients perspective, John, the thing that everyone wants to know is now you can identify the stem cell that's probably the culprit behind recurrent disease, are we any closer to being able to get rid of it?

John Dick: Well, I think first of all we need to prove that contention, I think we need to understand the growth properties of these cells, we don't know whether they can lie dormant. Leukaemia stem cells really spend a lot of their time lying dormant and it explains why those cells can be swimming in a sea of anti-proliferative chemotherapy agents and they would survive and then be responsible for growth back. We need to determine what the growth properties are for these colon cancer-initiating cells.

Chris Smith: John Dick and before him Ruggero De Maria from the Italian NIH in Rome, describing how they've isolated tumour stem cells from colon cancers and these cells will, hopefully, provide useful clues as to how to better treat the disease in future.Coming up shortly we'll be finding out what it takes to reach the top of the world's tallest mountain. Also a new way to pinpoint reefs at risks from storm damage and the world's first molecular movie as scientists watch molecules twist and bend in real time. But first to the Human Genome Project which we all thought we'd finished but then along comes Matthew Hurles from the Wellcome Sanger Institute in Cambridge and he's found that far from having a complete genome, most of us probably have pieces missing from some parts of our genetic code and multiple copies of others. Nature 444, 428–429 (23 November 2006) ; Nature 444, 444–454 (23 November 2006)

Matthew Hurles: We've discovered that there's a type of variation, and it's copy number variation, in which large chunks of DNA in the genome can vary in copy number so that you can have two copies, I'll have one copy, another person can have no copies at all, in some cases.

Chris Smith: That sounds pretty dramatic because we're quite well acquainted with diseases in which you have too many of a certain copy of gene like, say, take chromosome 21, you have three copies of that and you get Down's Syndrome, so how do you rationalise that with what you found here?

Matthew Hurles: Well, chromosome 21 is a big chunk of DNA, it's tens of megabases long. What we find is that there's a middle ground where there are these chunks of DNA of the region of 50,000 bases to, say, five million bases which you can loose and actually have relatively little effect.

Chris Smith: Is that just because they're junk?

Matthew Hurles: Well, that's the interesting thing, many of these things are not just junk, they contain the bits of DNA that actually do the work, they contain all types of functional sequence, they contain genes, non-coding RNA's, things that we think are incredibly important but we don't know what they do just because they're incredibly well conserved between humans and fish.

Chris Smith: So how do we live without them?

Matthew Hurles: Very good question – we don't know. What we know is that we've taken 270 apparently healthy individuals and we've catalogued the amount of this type of variations of their genome and we've found that up to 12% of the genome can be varying in copy number amongst these individuals.

Chris Smith: Is the same true in other animals, not just humans?

Matthew Hurles: Absolutely, this is probably a general phenomena of most genomes and they can be tolerated in humans and certainly mice where we've looked. Some people have worked on chimpanzee genomes, so it's not something that's peculiar to humans; it's certainly common to all mammals.

Chris Smith: How did you stumble across it?

Matthew Hurles: Well, there have been some intriguing studies which have shown, on a small scale – maybe looking at 10% or the genome or looking at a few tens of individuals, where this kind of variation has been found, we decided the only way to understand how important it was, would be to take 100s of individuals and look over the entire genome.

Chris Smith: So, presumably, given that this is within your own DNA, you can trace this back in a familial fashion? Where you get these things from and where they're going?

Matthew Hurles: Absolutely, at the small scale we can show that you can trace it back to your parents. So we studied families and we showed that the chunks that were missing in the offspring could be found missing in the parents. But equally you can show that the pattern that you see over the whole genome of chunks missing and lost is actually indicative of your ancestry, so we looked at populations from Europe, from Africa and from Asia and we showed that you could actually cluster those individuals, if you didn't know which population they came from.

Chris Smith: Are there any pathological syndromes associated with it, though, when it really does manifest to something?

Matthew Hurles: There is a well known set of disorders known as genomic disorders where the genomic architecture pre-disposes that region of the genome to rearrange again and altering in copy number and we see that these kinds of regions are clustered around these duplicated sequences. But we do find there are known recessive disease alleles in amongst the variance that we find in these, apparently, healthy individuals because they are carriers for these diseases.

Chris Smith: Where do you think they actually come from? And it is a selection process, so some conceptuses will be just completely incompatible with life, and so they will just be deleted whereas others, which will contain copy number variations which are compatible with life, would slip through the net and be inherited?

Matthew Hurles: Absolutely. There's two processes going on, there's mutation generating the variation and selection removing it. Now mutation is probably generating this all over the genome and selection is removing it from certain regions of the genome and what we can do is we can show that, although they're spread over the genome and they do encompass functional sequences, they are biased away from functional sequences, so I suggest there is the action of selection removing some of these from the genome.

Chris Smith: Matthew Hurles who's found that we are much more of a genetic mish-mash than we first thought, with some genes going AWOL and others boosting their numbers without our knowledge. Now another person who is interested in genetics is UCL's Rebecca Forth who is trying to track down what makes some people better mountaineers than others. We dispatched Mike Hopkin to find out if he's got what it takes Published online: 9 October 2006;

Rebecca Forth: You're doing well, you're doing really well. Keep it going now, keep it going, keep those legs going, keep driving, keep pushing it [overtalking]

Mike Hopkin: That's the scary sound of me being put through my paces on an exercise bike by Rebecca Forth at the human performance lab at University College London. The aim is to find out whether an ordinary bloke like me has got what it takes to survive on the world's tallest mountain. I volunteered to take part in a piece of research called Project Everest which tests sea level dwellers to see whether some of us could scale the dizzying heights of the Himalayas without passing out. Besides pushing her guinea pigs on exhaustion on the bike her tests also involve starting her subjects of oxygen rich air to see how they cope and I can tell you, it doesn't feel very nice. I asked her to explain the science behind the sadism.

Rebecca Forth: Keep it driving, this is excellent, keep it driving, you are doing really well. Basically what I am trying to look at is the differences that we see in terms of performance on a mountain, see if we can actually show that those differences are attributed to differences in genotypes and there's a particular genotype that I'm looking at and I think that one of these types of genotypes actually shows that you're better prepared to go up Everest than if you didn't have it.

Mike Hopkin: What are you looking for in your study subject to try and find out whether they've got what it takes?

Rebecca Forth: Well, first of all I'm looking for very normal people to come in to be tested and then, from that, I'm looking at a different range of how people respond to hypoxia. So the lack of oxygen, whether they're very sensitive to it or whether they're not very sensitive to it, then I'll check their genotype to see if the one I think should mean that they're sensitive actually is the case.

Mike Hopkin: If you think this all sounds like lots of hard work then spare a thought for Forth's colleagues who, next year, will travel to Everest to do many of the same test on themselves on top of the mountain! Who would be enough of a nut job to actually do this?

Rebecca Forth: It's a collection of medics and scientists, but in there there are a lot of experienced mountaineers as well, Sandeep Dylan who is a doctor with the army, has climbed Everest twice and one of the other climbers, Mike Grocott, he used to work in Nepal for the mountain rescue, so there are experienced mountaineers but they do have the scientific background as well and they're out in ToyOy at the moment and they are, basically, using it as a dry run for the Everest trip next year, so they've got all the scientific equipment out there and the exercise test that you did today where we took you to exhaustion, they will actually be performing at various stages up Everest and, at the same time, they are going to be measuring the amount of oxygen that is actually in the subject's brains. At base camp there will be a lot of volunteers, I think 200 volunteers will be tested but as you get higher up it will be the actual climbing team who will be the subjects at the same time and it will culminate in an original recording of a blood-gas level at the summit of Everest, from somebody who's climbed it without any oxygen.

Mike Hopkin: And that's never been done before, presumably.

Rebecca Forth: Never been done before.

Mike Hopkin: And that's not hard to imagine why. But enough about that, what about me? Could I climb Everest? Well, the results of the genetic screen aren't in yet so I probably shouldn't pack my bags but it is really all about the genes anyway, surely being super fit could help to propel somebody up a mountain?

Rebecca Forth: Actually it doesn't correlate at all, so physical fitness doesn't relate to being able to perform on the mountain and, actually, it can be detrimental because if you imagine someone who is super fit, does lots of marathons, maybe cycles, maybe does triathlons and mentally they feel they can stretch their body to extremes and when you start climbing a mountain, whilst they can deal with the physical challenge in the sense of the incline of the mountain, they can't deal with the altitude and the change in the oxygen and if you are gung-ho about climbing the mountain in that way then you are going to suffer and those types of people do tend to suffer because they've tried to climb it too quickly, when you just need to let your body acclimatise.

Mike Hopkin: So even being a finely tuned athlete at the peak of physical condition might not do me that much good, which makes me kind of glad I didn't waste loads of time training, although it might have made the exercise bike a bit easier. It's tough work being a science journalist.

Chris Smith: I wonder who the poor soul is who's going to carry that exercise bike all the way to the top of Everest? That was Mike Hopkin being put through his paces by UCL's Rebecca Forth, who is trying to find out what maketh a mountaineer. You're listening to Nature's podcast from the 23rd November edition of Nature with me, Chris Smith. Now from the top of the world's tallest mountain to the bottom of the sea. Joshua Madin has come up with a way to predict the vulnerability of coral reefs to damage by storms and Tsunamis. Nature 444, 477–480 (23 November 2006)

Joshua Madin: We know that hurricanes and tsunamis can have devastating effects on coral reefs and what we did was try and think about corals as an engineer might think about a building, where wind can push over a building if it's not built in a strong way. So we used an engineering kind of approach to calculate the forces a coral is subjected to by wave or a storm surge or a tsunami and the probability of colonies being ripped from the seabed.

Chris Smith: Surely the hardest thing for any model to get to grips with all the different species of coral because there are so many different types?

Joshua Madin: That's right. Our model can deal with any kind of shape because shape is one of the factors used to calculate the coral's vulnerability at the wave forces and to show this in our study we chose a subset of different species that grow in very different ways. For example one of the species grows into more mound-shaped like colonies with broad bases. And, as you can imagine, these are fairly sturdy. Another species, however, grows into more table-shaped colonies with a narrow central stalk and this species was particularly vulnerable to wave forces.

Chris Smith: The thing is that the corals of different species are also distributed in different places across the reef, aren't they, so how does your model account for that too?

Joshua Madin: That's a good question, yes, vulnerability also depends where a coral grows on the reef and so what we did is we used a four decade long hind cast of auto motion over the reef which accounted for how a wave decays as it moves over a reef and then we could look at the thresholds imposed by these gradients in relation to the strength of the corals that lived over the reef.

Chris Smith: But in making a model like this can you be reasonably sure that it doesn't matter whether I live in Hawaii or the Great Barrier Reef or the Cook Islands, that your model is going to hold for wherever I am geographically?

Joshua Madin: So the model looks more specifically at corals as individuals and their particular shapes and their vulnerability to water as it rushes by a coral colony. The differences you're going to get when you go to different geographical regions are differences in the strength of the substrate to which these coral colonies are attached and also differences in the kind of wave regimes and these are elements that need to be looked at when you start exploring these patterns at larger scales.

Chris Smith: What groups of people would find this study useful and this particular model, how would it be employed, do you think, in terms of the big picture?

Joshua Madin: Well coral reefs are not only beautiful but they provide a lot of important resources to humans and therefore should be protected. So people who might well find this work interesting will be managers who can use this work to assess the vulnerability of their reefs. Also climate risk modellers can use our work to forecast how reefs might look under different future climate change scenarios and, possibly most importantly, this work is important to all of us who appreciate the beauty and diversity of coral reef ecosystems.

Chris Smith: Now just to play Devil's Advocate, Josh, if a hurricane is coming, it doesn't matter how much preparation you put in, it's going to wreck your reef, isn't it, so in what way is this model valuable in that respect?

Joshua Madin: I think this model is particularly valuable because a manager will be able to assess the vulnerability of their coral reefs and therefore look at possible economic losses due to these large disturbances, but also to plan strategies which will help the reef recover.

Chris Smith: Joshua Madin from California's National Centre for Ecological Analysis and Synthesis, describing his new model to help managers protect their reefs better from storms and tsunamis. And now to a storm of a very different kind, that's brewing quite close to home, in fact on Nature's shores. It's been sparked off by the publication of a letter from a Polish politician and Jo Marchant has the story. Nature 444, 265 (16 November 2006) ; Nature 444, 265 (16 November 2006) ; Nature 443, 890–891 (26 October 2006) ; Nature 443, 406–407 (23 November 2006)

Jo Marchant: Should Nature censor the views of its readers? Judging by the debate in the blogosphere this week, there are a lot of people who think so. It started last week when we ran a correspondence letter from Maciej Giertych, a Polish member of the European Parliament in response to a story we had published about an anti-evolution campaign being launched in Poland by his political party. Giertych denied he was a creationist but went on to list what he described as scientific evidence against the theory of evolution, including the idea that geological strata can form sideways and that dinosaurs co-existed with humans. The letter has already provoked protest from the scientific community, not just against Giertych but against Nature for even publishing it. On the popular Pharyngula biology blog there are now well over 50 comments on this, many of them saying things like "Nature seems to swirl down the sink" and "What in the world were the editors thinking?" So were we right in publishing the letter? I have with me Roger Stanyard, founder of the British Centre for Science Education which campaigns against the teaching of creationism in schools and Maxine Clarke, Nature's correspondence editor. Hello.

Maxine Clarke: Hi.

Roger Stanyard: Yeah hello.

Jo Marchant: Roger, you wrote on the ferengular blog that you were amazed that Nature decided to publish the letter, can you explain why you thought it was such a bad decision?

Roger Stanyard: There were two reasons for it, one it gives publicity to the creationists that allows them to state that they're being taken seriously by, what is in fact a very prestigious, world-class publication. I think there's actually another danger related to that, the particular person involved is political, his family are highly political and they've been involved in fairly extreme politics for a generation or so. I think there there's a second danger that it's going to be used as a political tool as well as a tool to proselytise creationism.

Jo Marchant: So, Maxine, you've heard Roger's reasons, why did you think it was a good idea to publish the letter?

Maxine Clarke: Well, the politician had been contacted for the news story that we published the week before and didn't answer the journalist's queries and then wrote into our correspondence section with his views. I judged that his views were interesting for our readers and my colleagues agreed and so we published the letter, along with another letter which was actually on the other side, as it were.

Jo Marchant: His views are obviously outside of the normal scientific opinions that Nature would ally itself to so why did you think his views were interesting?

Maxine Clarke: Because they are pretty outrageous and that he's actually an elected official and I though it was quite interesting for his potential voters to know that he felt this way.

Jo Marchant: Roger, would you not agree that, if a prominent politician has these views, it's good for voters and other people to know about that?

Roger Stanyard: Certainly but the audience of Nature is not the general public. What concerns me is that he's going to actually use the letter to justify his position to a much broader audience which, for the most part, are scientifically illiterate. I have to say, as an aside to that, that as a letter addressed to an audience of Nature, it was probably quite a good idea because the person was showed up, very well, to have extreme scientific views which are completely outside the mainstream of science.

Jo Marchant: So Maxine, Roger seems to have conceded that for Nature's audience it was a useful letter, do you think that we should be worried about how creationists or politicians might use this letter to a broader audience?

Maxine Clarke: Well obviously as editor of a Nature section, one has to make editorial judgements for the journal that you're publishing the letter in. I do accept that there's a wider agenda and that people can misquote or miscite an informal, un-peer reviewed letter to the editor as something which it isn't. The jury is out but Nature has published many, many correspondences in the 130 years that it's existed, many of which have been wrong headed, many of which have been wrong headed on this very topic and evolution is still a strong concept.

Jo Marchant: Okay, thanks both for that discussion and for anyone who wants to know more about the issue of creationism in Europe, there's a special report on the topic in this week's Nature.

Chris Smith: Thanks Jo, finally this week, we're off to the movies with Zurich University's Peter Hamm. He and his team have found a way to watch molecules in action as they change shape and move. Now this is a major step forward because, until now, we've had to rely largely on crystal structures which are fixed in position so they can provide only a snapshot of what a molecule might look like and do. The team use infrared spectroscopy in two dimensions to track the movements of key chemical groups and they can do it incredibly fast. Nature 444, 431–432 (23 November 2006) ; Nature 444, 469–472 (23 November 2006)

Peter Hamm: What we really want to do is to develop what I would call a molecular movie, we want to be able to see molecules move and, up till now, this is not really possible, in particular if you do it on really fast timescales, the fact is that molecules move on extremely fast timescales of pico seconds or even femto seconds sometimes and we know from theories that this is so, but it's very hard to make that visible by real experiment.

Chris Smith: Because, I mean, most of the time, when we think of things like enzymes, when we gain the 3D structure of them by, say, X-ray crystallography, you're just getting a snapshot in time, you're not actually seeing the dynamic behaviour of that molecule are you?

Peter Hamm: That's exactly true. So the established tools which exist in chemistry and biology, this is mostly X-ray catering [?] methods and also NMR mass spectroscopy, they provide aesthetic or a time emerged structure of this system, but it's clear that these are actually dynamic objects and we want to make this visible with the kind of work we do here.

Chris Smith: So how have you done that?

Peter Hamm: We developed something which is called two dimensional infrared spectrophscopy. The essential idea is that we measure an infrared spectrum, infrared spectra measures molecular groups in molecules, for example, something like a CO group and the idea of this 2D infrared spectroscopy is to spread out such an spectrum in two dimensions and what's happening then, whenever two vibrations are coupled to each other by some effect, basically by coming close to each other in space, when they are coupled to each other then there is a cross kick appearing in this 2D spectrum and this cross kick tells something about basically special affinity of these two molecular groups.

Chris Smith: So how fast can you see a molecule move?

Peter Hamm: In principle, like the spectroscopy, the time resolution the spectroscopy gives us is limited by one pico second or so, which is, for biological processes, super fast. I think I would say biologists would say that this is essentially infinitely fast.

Chris Smith: So how do you manage to resolve individual molecular groups within a big macromolecule so that you know what each of the different chemical groups are doing and where they're moving to, how are you actually seeing that in high enough resolution?

Peter Hamm: In a way that's actually a little bit of a problem, of infrared spectroscopy, as compared to, for example, NMR spectroscopy, this spectra resolution is not very high. The molecule we studied here is a relatively small one and for such small molecules it's resolved, we see one individual band for one particular CO group of the molecule and we can actually assign that by various methods so we know exactly which band corresponds to which group in the molecule.

Chris Smith: So do you think you'll be able to get this to work with bigger molecules, that's of course where you really want to go with this, to see an enzyme really chewing up a substrate, isn't it?

Peter Hamm: In a way, yes, this is the ultimate goal of it but it's going to be a hard way, we are working on this, we will have to work with labels, almost artificial labels and the one way which has been shown already, by other people that this is possible, to do labelling is with using isotopes, and with isotope labelling which can be put at very specific positions in such a molecule we shift recreational bands by a known amount and in this way we can identify this band.

Chris Smith: Peter Hamm, from Zurich University describing how he's used two dimensional infrared spectroscopy to track very rapidly the movements of very different chemical groups in a molecule to show how those groups move and interact with each another. Presumably if his movies were to be shown at the cinema, of course they would need to be X-ray'ted. Well on that cringeworthy note, that is it for this week. Thank you very much for listening and do join me next time when I shall be exploring the workings of a bizarre machine from thousands of years ago. Meanwhile, if you want to find out a bit more about any of the reports in this weeks programme, they're all available from our website at http://www.nature.com/nature and if you'd like to send us some feedback, the address is mailto:podcast@nature.com. For more science, in the meantime, this week's Naked Scientists podcast explores the science of Antarctica, we'll be diving into the deep freeze with a look beneath the ice of today and also winding the clock back 50 million years to a time when Antarctica was covered in forests and home to giant penguins, we'll also be finding out about the research projects that are ongoing down there right now.That's all in this week's edition of the Naked Scientists podcast which is freely available from http://www.nakedscientists.com. This week's Nature Podcasr was produced by me, Chris Smith with Anna Lacy and Derek Thorne. Until next time, goodbye.

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