Nature Podcast 29 June 2006

Introduction

This is a transcript of the 22 June 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: In this week's Nature Podcast – Dr Heal Thyself. We'll be hearing how Ron McKay and his colleagues are persuading the brain to self-repair after an injury.

Ronald McKay: We've shown that we can stimulate recovery by stimulating the endogenous stem cells that are in the brain.

Chris Smith: We'll also be taking a trip to the aquatic equivalent of the carwash with Redouan Bshary who's found that fish shop around for the cleaner that will give them the best deal.

Redouan Bshary: If the cleaner fish cheats then the incoming client will actually avoid this cleaner fish.

Chris Smith: Also, there are fresh insights into how prion diseases, despite being caused by the same protein, can trigger different diseases like Mad Cow Disease and Scrapie.

Jonathan Weissman: We took a pure protein and misfolded it into two confirmations and showed that the strains propagated robustly.

Chris Smith: And how did you spend the June 21st? Shortly we'll be joining Oliver Morton for a worldwide cross section of science on the solstice, including an unusual nutritional experiment in Denmark.

Oliver Morton: The barcodes don't tell you how much it costs but they tell you what the food content is so that they can monitor the eating habits of obese families.

Chris Smith: Hello, I'm Chris Smith. Welcome to the 29th June edition of Nature's Podcast. Now, as we've just heard, there's encouraging news this week that it might be possible to trigger stem cells in the brain to repair injuries caused by strokes. The finding hinges on using specific proteins to reactivate some of the cellular pathways that first helped to build the brain in the embryo. From the National Institutes of Health in Bethesda, Maryland, here's Ron McKay. Nature advance online publication 25 June 2006

Ron MacKay: It's clear we can stimulate very extensive increase in the numbers of stem cells following an injury. What we're using is a pathway of proteins that activate pathways that are extensively studied in development in cancer. And the most interesting feature of the report is that if we activate the notch receptor that the notch receptor is linked to the classic cancer growth pathway.

Chris Smith: How did you actually induce the lesions in the first place that you then wanted to make good?

Ron MacKay: Well, you basically go in and you just close off a particular blood vessel in the brain so that you have a very uniform type of injury. And then these animals were treated with proteins that bind to and activate the notch receptor and similar proteins that activate the FGF receptor

Chris Smith: And how do you get the proteins in? Presumably you have to inject them?

Ron MacKay: Yeah, we pump them in actually. We pump them into the middle of the brain. So the brain has a tube and there's a sort of hole in the middle of it and we put the proteins in the middle.

Chris Smith: So into the ventricle?

Ron MacKay: Yeah, exactly.

Chris Smith: And is it just a behavioural measure then? Do animals seem to be performing better or have you actually done the histochemistry to show that you've got stem cell in migration and then recapitulation of different bits of the brain?

Ron MacKay: We've done both and it's clear that we get benefit by both measures. What's not clear is how the two measures relate to each other. It's likely, you know, that in any of these real sort of in vivo settings, where you're really trying to model a disease, there's more than one response to the treatment that you need to understand. Here there are at least three different tissues. One is the cells of the brain. The second is the cells of the blood vessels – the vascular system. And the third are the cells of the immune system. And it's possible that all three are showing a response. That brings me back to the possibility that the notch ligands are activating a very fundamental set of responses. If that's true, we're really in luck.

Chris Smith: I guess the thing that stands out most in this is given that the body clearly has the capacity, on the basis of what you've found, to make good some of this damage, why doesn't it happen already?

Ron MacKay: I think the answer to that is really interesting. If you were a mammal you would need a lot of energy. You can't sit under a rock for six weeks and get better. Now, if you're a lizard you can. You can sort of sit around, you don't use up much energy, your tissues can recover and then you can go off about your business. But if you're a mammal that's not an option, and, in fact, not only can you not sit around you pretty quickly become somebody else's lunch because they can't sit around either. So in mammals, it seems to me, what's happened is that injuries of this type you've developed a way of very rapidly shutting them down and if you survive you survive but there's no selection for regenerative response to major brain injuries. And so that, it seems to me, is why we don't normally have it. And with a bit of luck what we're doing now is stimulating such a response and in the conditions that human beings live in you can take care of somebody for the several months it will take to allow regeneration to occur.

Chris Smith: The man who is pushing brain repair up a notch. That's Ron McKay from the National Institutes of Health in Bethesda, Maryland.And now for a paper from last week's edition of Nature which has helped to shed some light on a grey area in our knowledge, or perhaps that should be black area because John Miller from the University of Michigan has uncovered how, paradoxically, black holes can produce half of the light in the universe and it's all down to magnetism. Nature 441, 953–955 (22 June 2006) ; Nature 441, 938 (22 June 2006)

John Miller: Black holes, matter falling into black holes, that process can actually be incredibly luminous but the actual mechanisms which make that process luminous and which can actually contribute up to half the light in the universe, those mechanisms haven't been clearly revealed before. I think what our observations show is that that process must be fundamentally a magnetic one.

Chris Smith: But what's actually generating that light?

John Miller: It's the process of gas falling onto the black hole, at a high mass transfer rate onto the black hole. The gas settles into a disc structure, something that's sort of familiar to common experience when you see a picture of a nearby galaxy. It's sometimes flattened and pancake-like. These discs that we have around black holes are different. They're not made up of individual stars but sort of a plasma gas and as the gas falls into the black hole frictional forces heat up that gas and the gas grows at a characteristic temperature. In this case the characteristic temperature is in x-rays.

Chris Smith: And the light can still escape from the black hole?

John Miller: That's right. One thing that's counterintuitive about this result is that gas falling into the black hole can glow very brightly until it crosses that event horizon that many people know about when we talk about black holes. Once a particle or a photon crosses that event horizon surely it's never heard from again but until that moment light can escape from matter and even matter can escape from its orbit around the black hole.

Chris Smith: And you think the process that's driving that is a magnetic one?

John Miller: Yes. That's what our observations indicate. The frictional force in the accretion disc, which makes this radiation possible and which makes it possible for the matter to fall onto the black hole smoothly in the first place appears to be a magnetic one. And we've inferred that by looking at a wind that's blown off of the accretion disc and we find that that wind must be driven by magnetic forces.

Chris Smith: How can you see a wind though? What are you looking at?

John Miller: What we actually look at is absorption through the wind that's blowing off the disc. If you like, you can imagine a wind that's almost like steam coming off of a pancake in one sense except the steam coming off of our pancake isn't rising upwards. It's coming off sort of along the plane of the pancake itself. What we do is we look through this steam or this wind and we see absorption in characteristic elements in the x-ray band. And so we can infer quite a lot about the gas in this way. We can infer its temperature. We can infer its density. And if we gather all this physical information we're then able to try and assess how is that wind is blown off the accretion disc in the first place. Our conclusion is that in this case it really must be magnetic.

Chris Smith: You looked at one sort of typical black hole to make these observations but do you think that this is the exception rather than the rule?

John Miller: It's always possible. I suppose that must be said. I tend to think not. We've seen similar winds in other black holes but just in a little less detail. So what made this observation special was we happened to look at a source that was very bright so we got exceptional detail. And it was a very long observation, which helped as well, but this black hole bears many important and, I would say, overwhelmingly strong similarities to other black holes, which I think makes the result important for other black holes as well.

Chris Smith: John Miller from the University of Michigan. And now back to Earth. The summer solstice and what scientists worldwide are up to on the Northern Hemisphere's longest day. Speaking with me on the 21st June, here's Nature's Oliver Morton.

Oliver Morton: Some while back some of us were kicking around ideas and we thought it would be really nice to try and sum up the scientific world in just one day and the question then became what day we should use. One answer came back that maybe we should use the summer solstice because at least for those of us in the Northern Hemisphere, which is most of us when it comes down to it, that's the longest day so we can maybe get as much science as we could possibly cram into 24 hours. That's how it started off and from that basis we just put out feelers to people around the world. We used our own news staff for all sorts of things and just tried to pick up moments from all sorts of days, some ordinary, some extraordinary, that go together to make up a portrait of what the scientific world does in just 24 hours.

Chris Smith: Have there been any interesting things that people have sent in to you?

Oliver Morton: There've been remarkable things. For instance, it just happens that today is the day that the cervical cancer vaccine has been approved for use in Australia. We have the man who developed it out in Australia talking about the press conference he went to about that or we have the latest deepest images from the Hubble Space Telescope. Here's a lovely one. We have one of the wine technicians at the Bavarian Health and Food Safety Authority setting up a laboratory sample so it can sample wine while he's out drinking it on his office annual away day when he'll be out at a vintage car museum. We've got people talking about super computing in Paris and talking about making clocks out of light in Ontario.

Chris Smith: My favourite one is the supermarket run by the Department of Human Nutrition.

Oliver Morton: Yes, the supermarket run by the Danes. That's absolutely wonderful in which the barcodes don't tell you how much it costs but they tell you what the food content is so that they can monitor the eating habits of obese families. Yes, that's terrific. And there are all sorts of things. Mostly it's not about finding particularly spectacular things except when you stop and look at this many aspects of it science, as a whole, just comes up as being more spectacular than we even thought. It's not just about the individual discoveries. It's about this extraordinary planet wide venture of hundreds of thousands of people trying to understand the world, looking out at other worlds. It's quite an extraordinary impression that I think the pages give.

Chris Smith: So you've done the solstice. What are you going to do next? Do you think maybe how scientists are spending Christmas or something?

Oliver Morton: No. I think this is pretty much a one-off. We've chosen one day and I think we've done it all the justice that we could. Yes, it's a special day but also, as Dickens said, "it's a day like any other" and that's what we're celebrating because, basically, all the days are remarkable.

Chris Smith: And people can read this in this week's edition of Nature?

Oliver Morton: Yes, it will be in the 29th June edition of Nature. We're getting it in just one week from start to finish and it will also be, of course, on the website.

Chris Smith: And is it just pieces of text or will there be other things to complement the insight into peoples' days?

Oliver Morton: It's got text. It's got pictures. We may even manage a few other tricks up our sleeves.

Chris Smith: A solstice in the life of a scientist. That's Nature's Oliver Morton.Nature's Podcast – bringing the world of nature to life.

Chris Smith: This is the Nature Podcast from the 29th June edition of Nature with me, Chris Smith. If you'd like to find out more about any of the reports we're discussing, they're all available on our website at http://www.nature.com/nature. There's also a text transcript to accompany this show, which is available at http://www.nature.com/podcasts and if you'd like to send us any feedback then drop us a line to mailto:podcast@nature.com.Coming up shortly, why it pays to be seen to do a good job – at least if you're a cleaner fish – and the first insights into the mechanisms of Mad Cow Disease and other prion diseases like it. But, before then, biodiversity. As humans intrude into more virgin territory, habitats are being fragmented and disconnected from each other, a bit like scattered oases in the desert. Models have been made to study this situation but what about animals that move from one patch to another? That's not really been looked at. Here's Kristin France. Nature 441, 1139–1143 (29 June 2006)

Kristin France: In the last ten years or so a lot of studies have shown that losing biodiversity or the number of kinds of organisms in a system can cause declines in important ecosystem processes like nutrient cycling and primary production, however, most of those studies have been done in single patches and mostly with plants and we were interested in how biodiversity of mobile organisms might affect ecosystem processes in patchy landscapes. So basically trying to make it a little bit more real world by adding space and by using organisms that can choose where and what they want to eat.

Chris Smith: What did you actually do here?

Kristin France: We used these small crustacean grazers that live in sea grass beds. And they're fairly small. You can see them without a microscope but they're fairly small. We basically constructed these little experimental landscapes, essentially out of five gallon buckets and, basically, we can contain them and we can identify how many we put in of each species and then we let their populations grow and they can swim back and forth between the different patches through a dispersal cord or sort of tubing.

Chris Smith: When you do this, what do you find, given the dynamic nature of the system?

Kristin France: We find that allowing organisms to move among the patches, picking and choosing where and what they want to eat actually significantly modifies the effects of biodiversity on ecosystem processes like how much sea grass there is in a system and how many grazers there actually are in the system. And, essentially, habitat fragmentation or eliminating the connections among the patches actually made the effects of declining biodiversity worse. Or, to say it another way, when habitats are fragmented and animals have difficulty moving back and forth between patches diversity is even more important.

Chris Smith: That sounds pretty serious. So what are the implications then for the real world?

Kristin France: If we want to apply all this work that we've done on biodiversity and ecosystem processes to the real world, which is obviously patchy and where organisms are obviously moving around, we need to think carefully about how connected patches are and how we can best manage a sort of dynamic landscape. And it turns out, not surprisingly, it's a bit more complicated than managing an isolated patch.

Chris Smith: Are you worried about the situation, given what you've found?

Kristin France: I am definitely worried, however, in some ways it was kind of encouraging because we found that both diversity and connecting patches had some beneficial effects for ecosystem processes and, in some ways, they actually kind of interacted so that when, at lower diversity, if you were connected, it might be sort of at a similar level than if you were at high diversity and not connected. So it may be that while we have to worry about those problems there may be sort of a trade-off and we can just kind of manage. Okay, well, we're going to be able to conserve lots of diversity here but we're a little bit worried about habitat isolation. We might be able to sort of manage for both and then there may be some scenarios where we can do a better job with one than the other.

Chris Smith: Why do you think you saw the result you saw?

Kristin France: I think there are two things. I think one thing is that we did use mobile animals that can pick and choose their habitat and, actually, when you allow them to move around there are things that they like to eat and things that they don't like to eat. And so we actually found that by allowing them to move around they ate what they wanted to eat and left behind what they didn't want to eat. That actually led to sort of a greater spatial variability in how much food was left in the system.

Chris Smith: Water World with a difference. Kristin France from the Virginia Institute of Marine Science, showing why the connections between isolated ecosystems are so important to biodiversity and the overall stability of habitats.Now, remaining with a watery theme, Redouan Bshary in last week's Nature found that when client fish present themselves for a spruce up by cleaner fish, which help to remove parasites, they pay very close attention to the service that the customers ahead of them are receiving. If the cleaner cheats by eating the client's mucous instead of his parasites, for example, he'll be shunned in favour of a more honest tradesman. Nature 441, 975–978 (22 June 2006)

Redouan Bshary: We discovered that client fish that visit cleaner fish to have their ectoparasites removed, that when they arrive at the cleaning station they actually pay attention to what the cleaner fish is doing to other clients. So if the cleaner fish cheats its current client by feeding on mucous then the incoming client will actually avoid this cleaner fish. So cleaner fish gain a kind of reputation. And the second part of our experiment shows that because clients look at what cleaner fish are doing cleaners are more cooperative in the presence of these image-scoring clients than in their absence. So they are more altruistic because observing clients will visit them afterwards and this is something that until now has only been found in humans.

Chris Smith: How did you actually do this experiment though?

Redouan Bshary: We did experiments in an aquarium set-up where we placed natural clients that had mucous and ectoparasties on them with Plexiglas plates where we put prawn meat and fish flakes. Now, cleaner fish prefer prawn meat over fish flakes and so we try to make them feed against their preference. This is the kind of problem and now with the plates we have them attached to a lever. We let the cleaner fish feed on the first plate. As long as it feeds on flakes the interaction goes on. And now the cleaner fish has to move on, do not feed on any prawn items on the first plate to be able to access the second plate because if the cleaner fish kind of cheats on the first plate we remove the second plate as well.

Chris Smith: And so that shows that they can feed against their will but then how does this prove that they change their behaviour in the presence of observers?

Redouan Bshary: Because we can have a control experiment where the second plate is left inside the aquarium, accessible to the cleaner fish, until the cleaner fish has eaten prawn item on this plate. So in the control situation the cleaner fish can cheat on the first plate and still access the second plate. In the experimental situation the cleaner fish has to be completely cooperative with the first plate in order to be able to access the second plate. And we find that only in the experimental situations cleaners are more cooperative than in the control situation.

Chris Smith: So, in the human context, does this mean the Good Samaritan wasn't so good after all and was actually doing it for what other people who were seeing what he was up to might think?

Redouan Bshary: This is actually also the general evolutionary explanation for the behaviour in humans that, in principle, one of the major future benefits of being altruistic, of helping other people, is that bystanders observe this action. In humans we have an additional option. We can talk about our good deeds. In the evolutionary sense we would argue that social prestige is a very good incentive to behave altruistically in humans.

Chris Smith: So it certainly pays to be seen to be doing a good deed. And there we were thinking that the Good Samaritan did it for all the right reasons.Now, fish and chips often go together but in this instance it's computer chips. Mercouri Kanatzidis from Michigan State University has uncovered a new form of the semiconductor germanium, which like silicone might have a variety of interesting properties when you shrink it down to the nanoscale. Nature 441, 1055–1056 (29 June 2006) ; Nature 441, 1122–1125 (29 June 2006) ; Nature 441, 1126–1130 (29 June 2006)

Mercouri Kanatzidis: We have been able to make a new form of a very basic semiconductor that is used all over electronics and so on such as germanium, which is related to silicone. Silicone is the semiconductor that is used in computers and various electronics. Germanium is just as important. We have been able to build a new form, using molecular chemistry of germanium, which may have some interesting properties.

Chris Smith: What's special about your new form and how have you done it?

Mercouri Kanatzidis: Let's talk a little bit about the old form which is a bulk dense crystalline phase that has been going for over 70 years and it has been refined and studied since the 50s. It is an exceptional electronic material but, say, for the last ten, 15 years, there has been interest in changing this form and making new forms. One example is polysilicone that has appeared maybe in the late 80s, early 90s and caused a lot of excitement because polysilicone has optical properties. The way that happened was the dimensions of the silicone material became smaller and smaller that it's in the nanoscale and then gave rise to the new optical properties. And so ever since we've been interested in trying to build germanium and silicone with very small dimensions.

Chris Smith: So how have you done it? What have you done?

Mercouri Kanatzidis: We thought maybe if we found a single ion of germanium or silicone, and say if it were an anion and then if we brought in a cation of the same substance we can combine them together in an organised fashion. The anion and the cation could combine forming a neutral germanium material and the challenge was to find such a soluble source and to do it in an organised fashion. What we did was we took a liquid surfactant that dissolves in an organic solvent and when it's in very high concentrations it organises in three dimensions over long distances and so the anion goes in between these organised micelles that the surfactant forms. And then when we add the cation the two combine forming a continuous network around the organised medium building up what is a porous network of germanium.

Chris Smith: And why is this new form much better than the existing form and how do you see it being used?

Mercouri Kanatzidis: It is not much better – it is a new form and the excitement is that because we now have made the dimensions so small we would see new physical phenomena such as new optical properties. We don't know very much about the form because we've just had it for a few months. So it's not as well studied yet as the other form, which has had a history of about 50 years. So it's not so much that this form is better than the old form. It's a new twist on an old material that may create new properties, not to have some of the same properties only better but new properties that the old material did not have.

Chris Smith: Mercouri Kanatzidis from Michigan State University announcing a new form of germanium with hitherto as yet undiscovered properties.Now, finally this week, BSE and other prion diseases. These are fatal disorders caused by the accumulation of an abnormal form of the nervous system's own prion protein. But since it's just a protein why should BSE cause a very different disease presentation than its relative in sheep, Scrapie, or the sporadic human Creutzfeld-Jakob disease? Adding a crucial piece to the puzzle, here's University of California San Francisco's Jonathan Weissman. Nature advance online publication 28 June 2006

Jonathan Weissman: We've addressed a central and probably the most enigmatic feature of prion biology and that's the fact that prions come in different strains or flavours. So a prion is an infectious protein, completely unlike a virus because there's no DNA or RNA in it. The idea is that the protein is infectious based on how it's misfolded into this toxic self-replicating form. But one of the central enigmas of the prion idea or hypothesis was that prions came in different strains or flavours and you could have what seemed to be the same infectious protein causing a very different type of disease. So a classic example of this is the Scrapie and Mad Cow. Scrapie and Mad Cow don't differ just because Scrapie is typically in sheep and Mad Cow is in cows. They're actually really rather different diseases. They have different pathologies and if you put them, for example, both of them in the mouse you get clearly different diseases out. So why is that so surprising?

Chris Smith: Given that the actual protein, the raw material that's actually feeding the process is the mouse's own prions, suggesting that the abnormal behaviour of the two things, the differential behaviour, must relate to the shape of the thing that started the disease in the first place?

Jonathan Weissman: That's exactly right. You hit the nail on the head. Strains are a very familiar thing from virology but if it's an infectious protein and the protein's encoded by the host and is identical what could be causing these strain differences. And, in effect, you had to do one of two things. You had to either say there was some other element in it that was responsible for these differences or you had to say that not only could a protein misfold into an infectious conformation but it had to fold into more than one infectious conformation, at least one for each strain. And, basically, we now know that the latter is true.

Chris Smith: How do you know that though, Jonathan? What's the proof here?

Jonathan Weissman: This has come from a number of studies, including our own studies, on this use prion system which I think because of the amenable nature of the system are the clearest. In effect, we took a pure protein covalently identical made in bacteria and misfolded it into two conformations and infected yeast with this and showed that you got these different strains and that these strains propagated true, robustly and that they were due to solely differences in the conformation of the protein.

Chris Smith: How do you misfold them? What's the actual method of making the protein take on the incorrect shape?

Jonathan Weissman: It turns out the protein does it all on its own. You make the protein and you have to keep it in very strong denaturants to prevent it from forming the infectious prion form. So all we do is remove these chemical denaturants and allow it to spontaneously form this misfolded form. And it turns out the conditions in which we produce the infectious form dramatically alter the conformation. The way I think of it, as an analogy, is a pachinko game, where you have the metal balls that are thrown up and then they bounce down and land in one of the wells. The wells are the different prion forms and if you tip the game one way or another you're going to land in a different well.

Chris Smith: And you reckon that yeast is a good model for what's going on in cows, sheep and, unfortunately, humans?

Jonathan Weissman: There is now very good evidence that similar differences in conformation underline human/mammalian prion strains as well. So we think it's quite a genuine phenomena of protein misfolding.

Chris Smith: Jonathan Weissman. And Jonathan also told me that, surprisingly, his work has also shown that the most virulent prions are also the least stable. So by falling apart the proteins can then seed fresh aggregates elsewhere in the brain. Perhaps then the best way to tackle the disorders might be to find ways to stabilise the protein rather than knock it to pieces.Well, that's it for this week and thanks for listening. Next time I shall be looking at seismology in Hawaii and witnessing the emergence of a new threat to Australia's koalas. Don't forget the new Nature newsblog, which provides a digest of sites and news stories and enables you to comment on them. You can also comment on this podcast, which is listed there, and to find it point your browser at http://www.nature.com/blogs.In the mean time, this week's edition of the Naked Scientist looks at, amongst other things, Benjamin Franklin's contribution to science and what you can catch in the average garden. That's the Naked Scientists podcast, which is freely available from http://www.thenakedscientists.com. The Nature podcast is produced by Derek Thorne and Anna Lacey and I'm Chris Smith. Until next week, good-bye.The Nature podcast is sponsored by Bio-Rad, at the centre of scientific discovery for over 50 years and on the Web at www.discover.bio-rad.com.