Nature Podcast 28 September 2006
The Nature Podcast from Nature, the international weekly journal of science, brought to you in association with Bio-Rad. Potent siLentMer Dicer-substrate siRNAs are now available with proven performance for guaranteed 85% gene silencing. Come take a look. On the web at http://www.bio-rad.com/rnai End
Chris Smith: In this week's show, the bacterium that can bring itself back from the dead.
Miroslav Radman: We've discovered a bacterium that, like Lazarus, can be brought back to life by reconstituting the genome from hundreds of little pieces.
Chris Smith: Also, if you thought spiders only made silk from their back ends, then you could be in for a surprise.
Adam Summers: When we put a large tarantula spider on a piece of glass and tilted the glass, it was producing silk not just from its abdomen, but from its feet, from the tips of its toes.
Chris Smith: And from one sticky subject to another: science in Iran.
Reza Mansouri: I hear sometimes from some of my colleagues, mainly from Europe, that they are not going to collaborate with a terrorist country like Iran.
Chris Smith: More from Tehran's Reza Mansouri coming up later. Hello, I'm Chris Smith. Welcome to this week's Nature Podcast. First today, meet the bacterial equivalent of Lazarus. It's a microbe called Deinococcus radiodurans and it's a name that's highly appropriate because this bug can tolerate having its genetic material smashed to pieces because it's evolved a way to put it back together again. It's an evolutionary trait that's enabled it to survive in some of Earth's harshest places including, it seems, in a tin of corned beef. Here's Miroslav Radman. Nature advance online publication 27 September 2006; Nature advance online publication 27 September 2006
Miroslav Radman: I'm happy to have made the discovery with my colleagues, on the 50th anniversary of the discovery of a fascinating bacterium called Deinococcus radiodurans that was discovered as a contaminant in canned meat that has been sterilised by enormous doses of ionising radiation.
Chris Smith: So it wasn't as sterile as people thought then?
Miroslav Radman: Well, it's sterilised against everything except Deinococcus radiodurans.
Chris Smith: Which suggests it's got some kind of way of persisting?
Miroslav Radman: It's got some kind of way of surviving doses that are three to five thousand the lethal dose for humans.
Chris Smith: And how on earth is it doing it?
Miroslav Radman: That was the question that lasted for 50 years and I'm so happy that we came with the mechanism. It is a by-product of resistance to desiccation which is a radical dehydration. It can maintain its potential to live even in the desert, burned for months by UV light of the sunlight, and when one looks at bacteria under these conditions, they are radically dehydrated, the genome is broken into 100 pieces, there's no trace of metabolism. These bacteria are clinically dead and principally, by re-assembling its genome from hundreds of little pieces, back in the correct order, and then starting re-synthesising all of the components, that's the mechanism of this "resurrection".
Chris Smith: How does it manage to put all the genome segments back into the right order because people who were doing the human genome project had taken donkey's years to achieve that feat?
Miroslav Radman: Yes, this is, indeed, a physical process that is formerly analogous to the contig assembly by the computer in the shot-gun sequencing of genomes like human genomes. The hardest work is done by computers. How do you assemble thousands or even millions of little pieces that have been sequenced in the correct order? And this bacterium does it with a few hundred pieces, with its own DNA in a physical way. So it's a computer-free contig assembly and the principle is really that you have to have at least two copies of the genome, and this bacterium does maintain two copies of the genome, even when dehydrated and starved.
Chris Smith: Are they individual circular chromosomes?
Miroslav Radman: Yes. They are individual circular chromosomes that are identical and now they are broken randomly, or close to randomly, by the ionising radiation, so you have pieces that overlap like ABC overlapping with CDE and then they, apparently, pair and use each other as templates to extend the strength, making long single-stranded tails which then find each other by Watson-Crick complementarity, and the genome gets reassembled.
Chris Smith: Given what this bug's capable of, the mind boggles what you think you might be able to exploit this for, in terms of practical applications.
Miroslav Radman: Well, if we could reproduce this process of fragmentary assembly in cell-free extracts, break the cells and still get the process, then we could dump into this Deinococcal soup, mix together genomes of insects, plants, bacteria and so on, and look for bacteria that would solve some of our problems such as bioconversion of energy, synthesis of new drugs like antibiotics and so on, and make something new that mother nature wouldn't make because of the barrier between species in normal reproduction in a normal sexual exchange of genes. That's one biotechnological dream that one could think of.
Chris Smith: So, next time you tuck into a pork pie, just think of the mosaic of interesting genetic sequences that could have been created by any Deinococcus radiodurans that might be in there. That was Miroslav Radman from the Université de Paris Renes-Descartes, introducing a Lazarus bacterium that can piece its genome back together, even after it's been shattered by radiation. Now if you're at all arachnaphobic, it might be time to cover your ears because Adam Summers, from UC Irvine in the US, has a sticky story to tell about big spiders. Nature 443, 407 (28 September 2006)
Adam Summers: We've found that tarantula spiders, at least one species of them, produces silk with their toes, so they actually are producing the same sort of silk that spiders produce to make webs, except that instead of producing it out of their spinnerettes, which are on the back end of the animal, what's called the opisthosoma or the abdomen, they are producing it out of those eight little legs that are up on the front end and, of course, they're tarantula spiders so there's nothing really little about them.
Chris Smith: But why would they want to do that. Why do they need the silk to come out of their feet?
Adam Summers: Tarantula spiders are terrestrial. They run around on the ground and we suspect that this silk is used to increase both friction and adhesion with their toes. Spiders have a really well known dry adhesive system that's quite similar to the gecko toe, but that doesn't always work and so having some sticky silk that comes out can give them a little more traction. And remember, these are great big spiders and they don't have a very well armoured exoskeleton, so if they fall, they're in real trouble.
Chris Smith: So the theory would be that they, first of all, glue themselves to a surface and then as they move along, they're laying down a line that can essentially be a prevention to stop them falling.
Adam Summers: Well no, not quite. So what you've just done is given a very nice description of what's called drag line silk and most true spiders will lay down a drag line, every step they take they glue down a little bit of silk behind them and if you knock them off a table or something, they'll just hang by this thread. That's not what's going on here. These threads are unbelievably short. It was only through, basically, happenstance that we managed to visualise them at all. They are on the order of one or two millimetres long coming out of the foot, and so they are really only visible if you're looking at the footprint that's been left behind in the event that the spider skids its foot a little bit.
Chris Smith: Is that what you did to see them?
Adam Summers: Well, we had a very lucky thing happen. One of the authors on the paper was in charge of getting spiders to walk on glass and we were then going to look at the footprints. And one day he sort of took a longer break than usual and left the spiders on a tilted piece of glass, and when he came back, these spiders, which don't like to climb on tilted glass, and so they sort of freeze and don't move, the spider had slipped backwards and as it slipped backwards, you could actually see this little bit of silk at the end of each foot, and once we'd seen that silk, we knew how to get it and how to visulalise it and so we were able to see it when they were walking normally and able to put it under the scanning electron microscope and visualise exactly what the fibres themselves looked like, as well as subject them to some chemical tests and see that they are just as difficult to dissolve as regular spider's silk.
Chris Smith: So what came first, actually the ability to spin silk from the abdomen or the ability to spin silk from the feet, from an evolutionary point of view?
Adam Summers: Therein lies the really interesting question and Cheryl Hyashi, who's at the University of California at Riverside and is a co-author on this paper, she uses genetic techniques to try and understand which of two scenarios happen. The spinnerettes, which make silk in all spiders, are thought to be vestigial limbs. Did those limbs have silk because all arthropod limbs have silk? Or, did the limbs gain the ability to produce silk because the hardware for producing it was already in the genome and it was being expressed in the spinnerettes?
Chris Smith: Adam Summers there describing how tarantula's produce silk from the tips of their toes. Shortly, east meets west as Iranian cosmologist Reza Mansouri joins us to shed a little light on science and politics in Tehran. And we've also got a unique insight into how evolution works and that's all thanks to some brewer's yeast. First, though, with a whirlwind round-up of stem cell technology, the perils of sloppy statistics and the frequency of hurricanes, here's Anna Lacey talking with Nature's Jo Marchant and Jim Giles.
Anna Lacey: Debate around the use of human embryonic stem cells has been raging for a number of years now and scientists have desperately been trying to find an ethical solution. Now, a news story in this week's Nature suggests a way of using dead embryos and bringing them back to life. So, Jo, how have they managed to do this? Nature 443, 376 (28 September 2006)
Jo Marchant: Well it's not bringing embryos back to life exactly, but what they wanted to do was try to develop a human embryonic stem cell line from an embryo that had, basically, that had actually died, that had stopped developing in culture. So they took 161 donated embryos which had been donated from IVF clinics and, although some develop normally, some stopped dividing after three to five days, some stopped dividing after six to seven days. And what they found was that from one of the embryos that stopped dividing after six to seven days, they were actually able to get a normal looking embryonic stem-cell line.
Anna Lacey: Well this sounds miraculous, but how did they know they were actually dead and they weren't just alive and they managed to coax them out in some way?
Jo Marchant: Well normally, the standard embryologist criteria for an embryo being dead is, basically, if it doesn't divide for two days. What this may do is stimulate debate about what it actually means for an embryo to be dead. I mean embryologists, for practical purposes, would basically say well, if it hasn't divided for two days, it's not going to develop any further. But ethicists and other people might have different views on that.
Anna Lacey: So how are they managing to do this then? What's the method behind it, behind being able to take the embryonic stem cells out of an embryo that, otherwise, would have been thrown away?
Jo Marchant: Well, it's just a normal method that you would use. They take a cell and culture it in the normal way that they would use to develop an embryonic stem-cell line. They said that when they looked at these embryos that had stopped dividing, some of the cells in those embryos looked deformed and looked damaged but there generally were also some other cells that looked perfectly healthy.
Anna Lacey: But how do they know they're definitely healthy and we're not going to have some kind of health implication further down the line, once they've been grown into something miraculous and put into a real person's body?
Jo Marchant: Well in terms of looking at the chromosomes and just looking at the general characteristics of the cell, it seemed fine. Obviously, it will take more research to characterise that further and make absolutely sure. But it seems fine at this stage.
Anna Lacey: But there are other ethical alternatives being published at the moment and a recent example is the Robert Lanza paper that was published in Nature. Why is this method, in particular, so special and are people actually going to buy it?
Jo Marchant: Well that's the big question really. I mean, I don't know if this is special compared to the other alternatives, but there are certainly lots of different things that people have been trying. One is a group who developed human embryonic stem-cell lines from a parthogenetic embryo so that's, basically, an unfertilised egg that developed into an embryo-like structure that never would have had the capability to develop any further. We've also got Robert Lanza's work where he took single cells from eight-cell embryos and was able to develop stem cell lines from those. But, in the long run, most people who are against embryonic stem cell research still seem to find problems with these. I guess, ultimately, it will come down to the different governments that don't want to fund human embryonic stem-cell lines and whether they will be convinced that this does solve their ethical objections.
Anna Lacey: Thanks Jo. Now sticking with Robert Lanza, publicity surrounding his paper was recently criticised because, although describing an ethical alternative for stem-cell production, the embryos themselves were eventually destroyed. But criticisms of Nature and other high level journals don't stop there. Talking now to Nature's Jim Giles.
Anna Lacey: Jim, how have Nature papers come under fire?
Jim Giles: Well, Nature, like many other journals, has been criticised in the past for getting its stats wrong. Stats are difficult and scientists often get them wrong when they file all their papers. So a couple of Spanish researchers in 2004 went through some papers from the British Medical Journal and Nature and they checked the statistical analysis and also looked at the way that numbers were rounded up. When they did that, they found a surprisingly high number of mistakes. Around one in three papers in Nature appeared to have some sort of statistical problem and around one in four in the BMJ had the same thing and when their paper came out, it prompted quite a lot of media coverage; headlines like sloppy stats shame science, that was in the Economist, and also prompted some journals, including Nature, to look at the way they did their peer review processes. Nature 443, 379 (28 September 2006)
Anna Lacey: So what's happened since then?
Jim Giles: Well recently, a physicist in the United States has gone back to the original paper by the Spanish researchers and looked at the statistics they used, and he's claiming that they, somewhat ironically, got their own statistics wrong and actually the rounding errors, which is one of the things that these ecologists were claiming was problematic in the papers, aren't errors at all.
Anna Lacey: Well, that sounds excellent news for Nature but not all of their paper was shown to be wrong, is that right?
Jim Giles: Yes. There were two key results in the original paper and one of them appears to be right. And even if an aspect of the original paper was shown to be wrong, I still think this new result illustrates just how hard it is for peer reviewers to spot statistical mistakes in papers. It's kind of interesting that the journal which published the original paper by the Spanish researchers, actually is a journal that's dedicated to publishing papers in research methodology, so you would think that the peer review there was done by people who have a fantastic handle on statistics and I'm sure they are, I'm sure they do, but that doesn't mean that mistakes can't creep through.
Anna Lacey: But statistics, however difficult they may be, they are important and it makes the difference between whether a paper is published or not a lot of the time, so do you think that all journals should be getting in their own dedicated statistician to do this for you?
Jim Giles: I think, certainly, that will improve the peer-review process, and if you look at the top medical journals, they tend to have statisticians that are paid to sit in on editorial meetings and can be involved in making decisions whether to accept or reject papers. The problem is that top medical journals make money and they can do that, but there's a huge number of small journals that are run on a shoe string and they can't afford to employ statisticians.
Anna Lacey: Now finally, this week there's some controversy surrounding the link between climate change and hurricanes, so what's been going on there?
Jim Giles: Well this paper goes back, really, to the political impact of Hurricane Katrina. It was seized upon by some environmental groups who said, look, this is the sort of thing that we're going to see more of due to climate change and, of course, President Bush's record on climate change has been criticised and the occurrence of Hurricane Katrina was used to attack Bush. Now, in the aftermath, it appeared that some of the political appointees in US government agencies were seeking to play down some scientific papers that linked global warming to increased hurricane activity. Nature 443, 378 (28 September 2006)
Anna Lacey: There are some people at the National Oceanic and Atmospheric Administration who don't agree with withholding information about linking climate change and hurricanes and they tried to release a statement saying that it may be contributing to hurricane intensity and that further research is needed. Why has that been withdrawn?
Jim Giles: Well, it's not a hundred percent clear. I mean, earlier this year, there were a lot of media reports saying that some researchers at that agency had been prevented from talking to the press and these were the researchers that appeared to say, yes, we believe there's a link between climate change and hurricane intensity. Several scientists complained about the way the agency was presenting the science, and in response to that, the agency said, okay, let's get a group of scientists together and try and work up a consensus statement that reflects a sort of diversity of views on this potential link. That appeared to be going fine. What we found out last week is that had gone up to the department of commerce, which is the part of the government that oversees the agency, and, at that point, it had been blocked. It's not really been made clear exactly why that's blocked, but given the fact that the government in the past has sought to play down that link, it will be seen by many people as another example of the Bush administration seeking to play down or even, in some cases, censor science that doesn't fit their political agenda.
Chris Smith: Nature's Jim Giles and Jo Marchant there, speaking with Anna Lacey. This is the Nature Podcast from 28th September edition of Nature, with me, Chris Smith. In a minute or two I'll be exploring the nuts and bolts of how evolution has fashioned two different strains of yeast. But first, how scientists have managed to produce a Bose-Einstein condensate in a solid material. Now a Bose-Einstein condensate occurs when atoms are cooled to temperatures very close to absolute zero. At this point, a large fraction of them collapse into the lowest quantum state which turns them into a super fluid and you can see quantum effects manifesting themselves on the macroscale. The principle was first demonstrated about 11 years ago using a cloud of rubidium atoms that had been cooled to within a millionth of a degree of absolute zero. But now, Benoit Deveaud-Pledran from the École Polytechnique Fédérale in Switzerland has achieved this feat in a solid material and at the much higher temperature of 19 Kelvin. Nature 443, 409–414 (28 September 2006) ; Nature 443, 430–433 (28 September 2006) ; Nature 443, 403–404 (28 September 2006)
Benoit Deveaud-Pledran: What we\'ve tried to demonstrate is that we did achieve Bose-Einstein condensation in solids. Starting ten years ago, Bose-Einstein condensation has been realised at very, very low temperatures, one micro Kelvin.
Chris Smith: But this was using gases, clouds of atoms and things?
Benoit Deveaud-Pledran: Clouds of atoms. And we\'ve tried to reach the same state within a solid with the possible advantage that the temperature is much more easy to access than the micro Kelvin temperature.
Chris Smith: So, what's the benefit of actually doing it in the solid, apart from the temperature difference, though. Are there other things that you can do as a result of having achieved this?
Benoit Deveaud-Pledran: We don't know yet. In principle, the advantage of doing it in a solid is that we should be able to manipulate these condensates in a much easier way. In fact, the holy grail of what we are looking for is Bose-Einstein condensation at room temperature. So you would not even need to cool the device.
Chris Smith: Could you also end up with a sort of superconducting system if you had something that was capable of generating these condensates at room temperature?
Benoit Deveaud-Pledran: If we find a way to have a charged particle, yes. For now, the particle that we have is neutral and I don't have a good idea, yet, to reach a superconducting system but, in principle, yes, there is no problem. Basically, this is what people have achieved with standard superconductors. This is another kind of the Bose-Einstein condensate.
Chris Smith: So how did you actually do this in the solid from first principles? What did you do to achieve this?
Benoit Deveaud-Pledran: The idea was to get particles that should be able to condensate, which we call the boson, and these particles should have a mass which is light enough to allow for reachable temperatures in a solid, and about 15 years ago, people discovered that in a solid, you could have a new state which is a copy of electronic excitation with photons, which we call polaritons, and these guys have a mass which is 10-4, the mass of an electron. These are incredibly light particles. In principle, these should be able to condensate at temperatures very close to room temperature.
Chris Smith: How are you doing it in a solid, though, because that obviously explains the particle nature, but what's the solid aspect of this?
Benoit Deveaud-Pledran: Okay, the solid aspect is that we have to confine both the electrons in the solid and the light in the same region of space. So, basically, we have a layer which is about 100 angstroms in thickness where we have the electrons sitting and this is in between two mirrors that have a rate of reflectivity of 99.99%, and so, in the same region of space, we have electrons and photons, to keep things simple, and they couple. And instead of having on one side electrons and on the other side photons, we have a coupling of the two particles, which we call polaritons.
Chris Smith: Benoit Deveaud-Pledran. He's produced a Bose-Einstein condensate in a solid material at 19 Kelvin.Now, with just 25,000 genes to play with and over 98% of our genome in common with a chimpanzee, a lot of what makes us different from other primates lies in how our genes are regulated. So how does evolution do this? To find out, Annie Tsong and Brian Tuch have been looking at two related yeasts, including brewer's yeast, Saccharomyces, and Candida. But when the dissected apart the molecular mating machinery in the so called A and alpha cells of these yeasts, the two had completely reversed the way their gene expression was regulated. A distant ancestor, though, showed signs of being a half-way house. Nature 443, 415–420 (28 September 2006) ; Nature 443, 401–402 (28 September 2006)
Annie Tsong: We've been looking at mating in yeasts and, yes, there are two mating types, A and alpha, and what we found is the group of genes, the A specific genes, which are on in A cells and off in alpha cells in every yeast that we looked at. Well, it turns out that their positively regulated in ancestor yeast but negatively regulated in modern yeasts.
Chris Smith: But why is this important?
Annie Tsong: Well, evolution of gene transcription seems to be a very important mechanism by which evolution occurs, and there are several lines of evidence for that. For instance, humans and chimps have more than 98% of their genome identical and in order to explain that, we think that many of the differences must be, not just in the genes themselves, because there are so few, but actually in when and where those genes are expressed. So we believe that this is a very important mechanism, generally speaking, by which evolution occurs.
Chris Smith: Well let's turn now to co-author, Brian Tuch. Brian, how did you go about dissecting what was going on in these two yeast families?
Brian Tuch: Well, the first thing we had to do was to identify what the A specific genes were in Candida. It was already known what they were in Saccharomyces cerevisiae, so Annie determined what they were in Candida albicans. From there, we determined which of those were likely, the ones that were shared between the two species, were likely to be the ancestral A specific genes. And from that, in many yeast species, we identified the regulatory element that controls those genes.
Chris Smith: Experimentally speaking Annie, what did you have to do to dissect out these pathways?
Annie Tsong: We used a number of techniques including gene knockout techniques, and micro array techniques, so what we were able to do was knock out the specific transcription regulator that was responsible for mating and then look at the transcriptional response of the cell, to having this important gene knocked out.
Chris Smith: And then there was a computation element, wasn't there Brian, on top?
Brian Tuch: Right, so once those genes were identified, we then mapped the genes that were orthologous between the two organisms as well as to 14 other related yeasts and then, with that in hand, we performed a motif-finding with a finding called MEME to identify the regulatory elements that controlled these genes. So these are elements which actually confirm the A specificity of these genes. They keep the genes on in A cells and off in alpha cells.
Chris Smith: And so, Annie, once you had that piece of information, how did you then take it forward?
Annie Tsong: So, one of the most fascinating aspects to us was the fact that we knew, historically, these genes were positively regulated in an ancestor but negatively regulated in modern Saccharomyces cerevisiae and its closest relatives. So, by looking at yeasts that are related to Saccharomyces and Candida to different extents, we found a modern yeast, which seems to have hallmarks of both positive and negative regulation. It's actually related to other two yeasts in a way such that it seems to be a transitional state. So, in a sense, we think that what happened, was the genes went from being positively regulated in an ancestor, to being dually regulated in a transitional yeast, and, finally, to being negatively related in modern Saccharomyces cerevisiae.
Chris Smith: But Brian, now you've reached this point, what are the implications for these findings?
Brian Tuch: One of the really interesting things, as Annie alluded to before, is that change from positive to negative regulation occurs seemingly without a whole lot of troubles; without disrupting the A specificae of the genes in the process. And what this means is that here we've identified a case where transcription regulation seems easy to evolve. And so I think that's interesting to the field, in general, and people have always believed that it would be easy to evolve transcription regulation and here we see it happening with a few small changes to the proteins, the transcription factors involved, as well as the genes they target.
Chris Smith: UCSF's Brian Tuch, and UC Berkeley's Annie Tsong describing how they've tracked the evolution of the mating gene regulation in yeasts. And those findings, naturally, give us clues as to how the regulation of our own genes must have changed over time.Finally this week, science in Iran. Nature's Geoff Brumfiel caught up with cosmologist, Reza Mansouri, from Sharif University in Tehran, to discuss, amongst other things, what's obsolete about the way they treat science in the Muslim world.
Reza Mansouri: Roughly speaking, concept of science in the Muslim world is heavily based on the concept of theology and, through the course of time, the last 800 or, maybe, 900 years, it has been a reduced to theology. Science philosophy and international philosophy sciences, just that part which was relevant to theology, relevant to religion, you see, or used for religion, needed for religion, that was the only part that we are allowed to teach.
Geoff Brumfiel: I wanted to turn now to a difficulty facing Iranian scientists, which is the issues surrounding Iran's strained relations with the West. How has this affected the way science is done?
Reza Mansouri: I remember it was, maybe, about 50 years ago, once we wanted to subscribe to Science magazine. We received the reply: Science is not to be sent to Iran because of political reasons, that and that and that. Even now, I hear sometimes from some of my colleagues, mainly in Europe, that they are not going to collaborate with a terrorist country like Iran, which is ridiculous, but anyhow. These are some of the reactions from the scientific part of our communication. But many of our colleagues have difficulty to getting visas for different countries, or attend some of the scientific meetings. But the world is big and there are many, many possibilities and we have tried to use all of that, so not to be isolated in science, and therefore, even though we have had restrictions, we could do something to flourish science in Iran and I hope that the restrictions will be less and less in the future.
Geoff Brumfiel: The main reason for the current strain between Iran and the West right now, is a scientifically-related programme, Iran\'s nuclear programme. As a physicist in Iran, as a member of the physics community, what are your views on Iran's nuclear programme?
Reza Mansouri: First let me say that the restrictions are surely not due to that solely, because we have had, even before any problem we had with regard to nuclear issues, we have had these restrictions after the revolution in Iran, you see, so now, we had issued, I mean the Physics Society of Iran, I was in prison at that time, issued a statement about nuclear issues of Iran three years ago. I would say the major point in it is that we urge our government to bring more rationality in all aspects of nuclear issues, you see, that's a major point.
Geoff Brumfiel: This is a bit of a delicate issue, but how closely tied are academic physicists to the nuclear programme in Iran? Is it a completely divorced government situation or, have physicists helped out with it? What's the relationship there?
Reza Mansouri: Yes, it's almost no relationship and I would say the nuclear issue in Iran has almost nothing to do with science and with physics, it's a little bit of chemistry and technology. It's not physics and it's not science. But I would say everyone who understands a little bit of physics and science knows that this is just an old technology, not even a new one, and not a high technology.
Geoff Brumfiel: So what is going on with string theory in Iran? Why do I see so many string theory papers coming out of Iran?
Reza Mansouri: That's a very interesting question. I remember exactly the beginning of the revolution, some old colleagues just sat together and spoke about what we could do for Iran. Is it understood that we have to look for excellence, in some areas that we may be strong and that we may get strong at that so that will be the field of physics. So we began with that. It happens that the most active field physicists in our country were working on the string theory at that time. So they tried to be of a school, so to speak, and we did know that that was the only way which was somehow independent of all these political fluctuations regarding war, regarding cultural revolution, all that, and we really tried hard to build up schools. So we have it now, string schools, so to say somehow.