Nature Podcast 24 August 2006

Introduction

This is a transcript of the 24 August 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.

There is a clarification associated with the audio and transcript edition of the 24 August Nature Podcast.

Advertisement

The Nature Podcast, sponsored by Bio-Rad. From detection to analysis, Bio-Rad provides the most complete selection of RNA interference products. Come take a look on the web at http://www.biorad.com/rnai.

Chris Smith: This week, a way to make embryo friendly human embryonic stem cells.

Robert Lanza: What we have done, for the first time is to actually create human embryonic stem cells, without destroying the embryo itself.

Chris Smith: A neutron star with a strange story to tell.

Scott Ransom: So we found very strong, strange radio emission from a neutron star that has some of the strongest magnetic fields known in the galaxy.

Chris Smith: And keeping it in the family, how amoebae facing hardships stick together, but only with their relatives.

Natasha Mehdiabadi: What we found is that they actually prefer to form fruiting bodies with kin.

Chris Smith: More on that story later. Hello, I'm Chris Smith. Welcome to this week's show. Now, if you're a regular listener to the Nature Podcast, then you might remember me talking to Robert Lanza, from Advanced Cell Technology, and he told me last year, about his approach to making ethically acceptable stem cells. http://www.advancedcell.com/, Nature 442, 858 (24 August 2006)

Robert Lanza: We have shown that you can generate embryonic stem cells, using a method that does not interfere with the developmental potential of the embryo, and we have actually done this in the mouse model. It will take up to a year, or possibly longer before we can repeat this in humans. Of course we won't know for sure, until we do the experiments.

Chris Smith: He collected single cells from early stage mouse embryos, and then used those cells to produce pools of stem cells, but most importantly the donor embryos weren't harmed in the process, and the same trick could be used with cells collected from early human embryos, for the purposes of PGD, or pre-implantation genetic diagnosis. Well, that work has now been completed, and earlier this week Robert told me what he's found.

Robert Lanza: We have shown that we can not only generate stem cells without destroying the embryo, but that that remaining embryo also has the potential to go on to create a healthy hatching blastocyst.

Chris Smith: How is that achieved, Robert?

Robert Lanza: Well, what we're actually doing is removing a single cell from an eight-cell stage embryo, and then we actually culture that cell in the petri dish, and are actually able, though various manipulations, to create stable embryonic stem cell lines.

Chris Smith: Are you satisfied that those cells that you generate are pretty much normal? In other words, they have normal genotypic and phenotypic characteristics?

Robert Lanza: Yes, it appears as though these cells are absolutely identical to all the other human embryonic stem cell lines we have in the laboratory, including the so-called presidential stem cell lines. They differentiate into all three germ layers, they are totally normal karyotypically, and they also are able to turn into the different germ layers, in both teratomas and embryoid bodies, and through various other techniques that we've studied. In fact we've been able to turn these into endothelial cells, into vascular structures, into retinal pigment epithelium. They appear to be absolutely normal in all respects.

Chris Smith: And do they appease President Bush's objection to the fact that you're destroying life, to create or further life, with traditional technology?

Robert Lanza: Well, as you know, the president objects to the fact that you would be sacrificing one life to save another, and in this instance there is no harm to the embryo that we're biopsying.

Chris Smith: And the fact that you say this could be used as a useful source of stem cells, in order to repair an individual in future, but not everyone's going to have PGD done are they, though?

Robert Lanza: This is correct, but the important thing about embryonic stem cells is that they are immortal, so that if you generate, even a few dozen lines, those lines are immortal, and would allow us to proceed into the clinic, for instance, using lines that have not been exposed to mouse feeders, and using the newer technique. So I think the goal here is just to generate the lines that everyone would be comfortable with, and that, at least here in the US, we would be eligible for federal funding, and of course there are people who would prefer to actually use lines that may have been derived without destroying an embryo.

Chris Smith: So when will you be able to test these cells formally, and check out their clinical potential?

Robert Lanza: Well, we've already done this, I mean at least pre-clinically. I mean we've tested these cells in various animal models, and shown that the differentiated replacement cells that we have generated are actually functional. And again we have also studied these, in terms of all the various markers, and we have shown that these cells appear to be normal in all respects.

Chris Smith: That's Robert Lanza, from Advanced Cell Technology in Massachusetts, with a way to produce human embryonic stem cell lines that don't harm the donor embryo. Now sticking with the very small we move to the microbial world, and how bacteria can target proteins to specific regions on their cell surfaces. By studying two proteins, which are normally sent to different parts of the Streptococcus bacterium Gunnar Lindahl, and his team at London University have pinpointed how it's achieved. Nature 442, 943–946(24 August 2006)

Gunnar Lindahl: The background to this is that we have been interested in the problem of how proteins are secreted from living cells, and we have been using bacteria to study this problem. It's well known since many years that most secreted proteins have a so-called signal sequence, which promotes secretion with the protein at the cell membrane, and this signal sequence is located at one end of the protein, and it is cleaved off during the secretion process. What we describe is that the signal sequence may not only direct the protein to the membrane, for secretion through the membrane, but that the signal sequence may also contain information that directs the protein to one specific part of the cell.

Chris Smith: Because most people will probably think that bacterial cells are pretty much homogeneous, right around the cell, and it doesn't matter which end of the cell you look at it's pretty similar.

Gunnar Lindahl: Yeah, exactly, and that I think is the textbook version that the protein has a signal sequence and that will promote secretion of the protein anywhere in the cell, or around the cell, and so that's the take home message of our article I think, that that's not true, and that the signal sequence may direct the secretion of the protein to specific regions of the cell.

Chris Smith: So which regions of the bacterium in particular does it send things to?

Gunnar Lindahl: We have been studying two regions of the bacteria. One is the so-called division septum, which is the middle of the cell, where the cell divides to form two daughter cells, and the other region is the poles, which are opposite from the division septum, and we have been studying two proteins, which are preferentially secreted in these two regions. That is, one protein is mainly secreted at the septum, and other protein is mainly secreted at the pole.

Chris Smith: So how did you home in on the bits of the signal sequence that make it go to these specific parts of the bug?

Gunnar Lindahl: Well, this goes back to an observation, which was made almost 40 years ago, by a distinguished American microbiologist, Emil Gotschlich at the Rockefeller University, and he and his group discovered that famous bacterial proteins, called M Protein, of Streptococci is preferentially secreted at the septum, but the mechanism of this has remained a complete mystery, and I've been intrigued by this observation for many, many years, but we haven't had the tools to study this. But however, a few years ago we did find another protein secreted at the poles, and that allowed us now to start comparing these two proteins. The one protein, which is secreted at the septum, and the other one is being secreted at the poles.

Chris Smith: So if you do the obvious experiment, which is you swap the signal sequence from one protein to the other, can you make the one that normally goes to the septum go to the poles, and vice versa?

Gunnar Lindahl: That's exactly the experiment, which my colleagues here in my group have done, and that was beautifully, and that key experiment shows, indeed that it is the signal sequences, which determine the site of secretion of the proteins.

Chris Smith: Does this mechanism highlight an important target for, say, novel anti-bacterials?

Gunnar Lindahl: Yes, I certainly think so, because most likely this is a mechanism, which is unique to bacteria. I mean it's not used by human cells, and that means that it's an obvious, and potentially very interesting target for antibiotics. But before such possible antibiotics can be defined we have to work out the molecular mechanisms in more detail first.

Chris Smith: London University's Gunnar Lindahl, on the trail of how proteins can be targeted to very specific sites on the surfaces of bacterial cells. Now let's shed some light on the world of neutron stars. Scott Ransom, from the US's National Radio Astronomy Observatory, in Virginia has solved the mystery of the magnetars. It turns out that they can produce radio waves, as well as X-rays, after all. Nature 442, 892–895(24 August 2006)

Scott Ransom: What we found, using a telescope in Australia we found radio pulsations from a neutron star, with an extraordinarily large magnetic field, and these objects we call magnetars, and this is effectively the first radio detection of pulsations from a magnetar.

Chris Smith: What's the significance of the fact that those pulsations are there, though?

Scott Ransom: The significance is that most neutron stars that we know about in the galaxy are radio pulsars, and there's only a very small fraction that are known as magnetars, and these are not seen in the radio. Those are all observed in the X-rays, and they're X-ray flux that we measure here at the Earth, with X-ray satellites. It's much larger than the radio pulsars, and so before there have been two different classes of objects, the radio pulsars and the magnetars, and this is effectively joining those two classes of objects.

Chris Smith: So it's the, sort of, grey scale in between?

Scott Ransom: Exactly.

Chris Smith: So where do those individual pulses come from?

Scott Ransom: Well, just as in radio pulses they come from the magnetosphere, so the neutron star has a very strong magnetic field, trillions of times stronger than the Earth's magnetic field, but very much like the Earth's magnetic field, it looks like a magnetic field like you'd get on a small hand held magnet, and particles bounce around in the poles of that magnetic field, and cause some kind of emission from the poles. So like a radio pulsar, we see that emission with a form of lighthouse effect.

Chris Smith: Do we know actually why they spin?

Scott Ransom: That's residual spin, from when the neutron stars were created in a supernova explosion, from the very mass of stars that were their progenitors. So you have a very massive star, and like a figure skater when they explode, when a figure skater pulls her arms in, so when the stars explode the star compresses, and we get rotation, it rotates more rapidly. But with the magnetic field, over a course of time that magnetic field causes a breaking of that rotation, and so it slows down, and this pulsar that we've found is rotating very slowly, actually, for a neutron star, only once every 5.5 seconds.

Chris Smith: But why do you think people haven't spotted this particular class before?

Scott Ransom: There's only about a dozen, maybe 20 magnetars known, and people have observed them with radio telescopes, very, very deeply, but no one had found anything, and we think that there's something strange going on in the magnetosphere of this particular magnetar. This one is a transient X-ray source, and so just a few years ago it turned on in the X-rays, and we think that had something to do with why it's now producing radio emission, whereas before it probably wasn't.

Chris Smith: So is that also something to do with what particles are knocking around in the magnetic field around it, then?

Scott Ransom: We think so, yes, so when the X-ray outburst occurred several years ago, it probably, somehow tweaked at a crust of the neutron star, which tweaked the magnetosphere, and caused a lot more particles to be bouncing around in the Magnetosphere, and those particles are probably what's now causing the radio emission.

Chris Smith: There must be quite a strange phenomenon, though, because the gravitational field there must be incredibly intense, and so it's surprising to me that anything really can drift around outside the neutron star?

Scott Ransom: Yeah, that's right, but the reason why that can happen is that while the gravitational force is extraordinarily strong, and I mean these are the closest thing we have to black holes, without being black holes, the magnetic fields are even stronger. So, since the electro-magnetic force is stronger than gravity, because of these incredible magnetic fields, it generates incredible electric fields when the thing rotates, and also when the magnetic field gets moved by the crust shifting, and that can cause charges to be moving all over the place, even though gravity is so strong.

Chris Smith: Scott Ransom, with a very unusual, slowly spinning magnetar, which bucks the trend and pumps out radio pulses, as well as X-rays. Nature's Podcast, bringing the world of nature to life.Coming up shortly, the largest elements you could ever hope to make, researchers push back the date when Earth became oxygenated, and amoebae that liked to keep it in the family. First though, how do you like the sound of citizen science, or garage chemistry? Well, that's where scientists that were meeting at Google's headquarters last week think that the world of research is heading. Jim Giles went to meet some of them. Nature 442, 848 (24 August 2006)

Jim Giles: I'm just back from the Google headquarters, in Mountain View, California. I was lucky to have been part of a really interesting meeting. A gathering of around 200 people from different areas of science, engineering, and commerce, who had been invited to spend a weekend at Google and discuss any topic they liked. The idea was to throw together a bunch of interesting folk, without much of a structure, and see what they came up with. Anyone there could propose or present a session on any topic. We had debates on everything, from the future of human evolution, to the need for scientists to take more risks, and one interesting topic that came up was that of citizen scientists. The idea that normal people can collect data and run experiments, so I dragged a few of the participants away from the debate, to hear what they thought about the potential of this new concept. One option is for people to become data collectors. It sounds like a boring job, but I spoke to Richard Newton, who is Dean of Engineering at the University of California, at Berkeley, who has a neat idea about how mobile phones could be used to collect data on things like urban pollution.

Richard Newton: The idea here is that, rather than sticking sensors up throughout the civil infrastructure, and having to maintain these network of sensors, what about if people volunteered to let us use their cellphones, as in fact a sensor platform. If people are willing to opt into this experiment, as they wander around in their daily lives, their phones would, on a regular basis, say, every ten to 15 minutes, or every hour, take a sensor reading of something interesting. The temperature, pollution level, background radiation, and things like that, and so they could send, through SMS, or some equivalent protocol, a little package of information, to a database that contained location, time, and the sensor reading.

Jim Giles: Richard's idea sounds like it has a lot of potential, but there's no reason why citizen scientists can't do more than just collect data. I also met up with Janice Dickinson, a Behavioural Ecologist at Cornell University. Janice is building on projects run by Ornithologists, who for several years have been getting birdwatchers to send in data on a species they observe. What she's done is taken this work to the next level, and got volunteers to actually run the experiments themselves.

Janice Dickinson: So what I've tried to do since I arrived at Cornell Laboratory of Ornithology is take the kind of work that I've been doing for the last 18 years, on Western Bluebirds, which is experimental field biology, in the field of animal behaviour, and see if we can use that as a tool to really excite people about animal behaviour, about bird monitoring, and about the experimental method. Essentially, teaching strong inference through citizen science, so we started this project called Personality Profiles, which is looking at a phenomenon called neophobia, fear of novel objects. What we asked participants to do is a controlled experiment, where they present the birds with a leaf, taped to the right of the entrance hole to the nest box, versus a chequered bow. We had, start with one or the other, depending on where they were born during the year, so they would randomize the order of presentation, and then they have to watch until one or both birds, if they can tell the two sexes, enter the nest box to feed. They also had to monitor the number of approaches and retreats from the box, before the bird first entered the box.

Jim Giles: That kind of citizen science project got a warm reception at the Google meeting, and it will be interesting to see how it pans out, but there were other citizen science ideas that unsettled people a little. To hear about one of those I spoke to Rob Carlson, a physicist at the University of Washington, who coined the phrase garage biology. I started by asking him what he meant by that phrase.

Rob Carlson: The ability to do science on your own is, in some sense directly related to your access to tools and skills, to accomplish whatever you want, and the costs associated with doing molecular biology have dramatically fallen in recent years. At this point it's a few thousand dollars, and it's very easy to accomplish relatively complex things in your garage, if you want. You could probably go a long way towards constructing new organisms in your garage.

Jim Giles: I think when a lot of people hear that, they're going to have this idea of some, sort of rogue scientist cooking up some kind of pathogen in their garage, and perhaps using it to launch a bio-terror attack. Is that the sort of thing you're saying is possible?

Rob Carlson: It's certainly possible. It would be quite dishonest of me to portray it otherwise. It's improbable; it's very hard right now. It will, of course get easier, but the thing to consider there is that the threats will always increase. It doesn't matter that you can do this in your garage now, because we have plenty of evidence that people outside the country, say, have attempted to do that sort of thing, and I don't see that regulating it is going to make us any safer.

Chris Smith: And on the subject of citizen science, does anyone remember the young man in America, with an interest in radioactivity, who inadvertently built a fast breeder reactor in his garden shed, about ten years ago? Jim Giles there, reporting from Google's headquarters in California. And now to the field of super heavy elements. Elements produced by adding more protons to a nucleus, but how large can we go and how do we get there? Liverpool University's Rodi Herzberg. Nature 442, 896–899(24 August 2006) , Nature 442, 876–877(24 August 2006)

Rodi Herzberg: We investigate the question, what is the heaviest possible element on Earth, and if you cast that in a nuclear physics context, the question is how many protons and how many neutrons can you ultimately fuse into a bound heavy nucleus?

Chris Smith: But what actually constrains that under normal circumstances, and why can't you make bigger and bigger elements?

Rodi Herzberg: Protons are themselves positively charged, and since like charges tend to repel, once you put about 100 protons or so together, the nucleus tends to just rip itself apart and fission under that influence of the coulomb force. Now, if you want to make heavier elements you need to rely on quantum mechanical shell effects that give you extra stability, such as, for example, in the noble gases.

Chris Smith: But how does that actually work to stabilize things? Do we know?

Rodi Herzberg: If you have a closed shell configuration that means you get a lot of extra binding energy, simply because all the nucleons sit snug, and have partners, and no loose end to carry off. If you then add another one, that one is very loosely bound, so that mechanism of how to create stabilization from closed shells is very well understood. What is a key question now, especially for super heavy elements, is what are the numbers that you need, and what shells do you need to fill, in order to get such stabilization?

Chris Smith: But how do you propose to go about making these things?

Rodi Herzberg: In our case we have studied whether the shell closure at 114, proton number 114, that is predicted by theory, can actually come about, and what we have done is we've gone on a slightly indirect route, since the direct approach, which is to fuse two heavy nuclei and create them, faces the problem that you need a lot of extra neutrons. You have to go slightly around about, and indirectly, and the way we do it is we use deformed, slightly less heavy nuclei. The trick there is if you deform a spherical nucleus, the energy levels that are important, some of them come down in energy, and some of them go up, so you can actually gain access to a state that you would otherwise require 115 protons to actually put the first one into, but in a deformed nucleus you can do that with 102, or 103.

Chris Smith: What about isomers?

Rodi Herzberg: Well, isomeric states, and that is very long lived nuclear states, play a very important role everywhere in the nuclear chart, but it has been suggested that, for example, in super heavy elements it may actually be isomeric states that are more stable than the ground state, so they are experimentally wonderful things, because they give you that extra time to transport a nucleus, that still has energy left to do something interesting, to a place where we can actually study it. So these isomers really are the key thing to this research.

Chris Smith: So now you've got this far what are you going to look at next?

Rodi Herzberg: Well, the key thing here is that we have found a method where we can use isomeric states in deformed fermium and nobelium uclei that are experimentally very accessible to us today, and we can now use this to gain additional confidence in the data that is required for theories to actually latch onto, and give reasonable predictions for where the spherical superheavies will lie.

Chris Smith: Rodi Herzberg, from the University of Liverpool, describing how isomers of heavy nuclei could hold the key to understanding the next generation of super heavy elements. Now, another use of isotopes is in working out when Earth's oxygen rich atmosphere came along. Sulphur undergoes what's known as mass independent fractionation of its isotopes, and the only process known to cause this is the destruction of atmospheric sulphur compounds by ultraviolet light, and because ultraviolet light is stopped by the Ozone Layer, which comes from atmospheric oxygen, of course, the absence of mass independent fractionation in the geological timeline, must indicate when oxygen levels first began to rise. Until now most people believed it happened about 2 1/2 billion years ago, but now Hiroshi Ohmoto, from Penn State University has analysed almost 3 billion year old marine shales, from Western Australia. The samples lack any signs of mass independent sulphur fractionation, pushing back the time when the Earth first had an oxygen rich atmosphere by a further half a billion years. Nature 442, 908–911(24 August 2006) , Nature 442, 873–874(24 August 2006)

Hiroshi Ohmoto: What we discovered was the possibility that the atmosphere, sometime in the archaean, before 2.5 billion years ago, could have been oxygenated, which contrasts to the current dogma, which says the atmosphere was entirely anoxic, until about 2.4 billion years ago.

Chris Smith: So what have you done to challenge the dogma, and how have you done it?

Hiroshi Ohmoto: Well, there's a number of geological evidence people have used, to examine the oxygen level of archaean time, looking at the rock records, or the presence or absence of certain minerals. However, the most currently popular method is to use sulphur isotopes, as a tracer of atmospheric oxygen level.

Chris Smith: So how does that work? What's happening to the sulphur, in order to work out how much oxygen there was in the atmosphere?

Hiroshi Ohmoto: If the sulphur has four stable isotopes, normal chemical reactions produce these types of isotopic ratio in certain relationships, in what we call mass dependent fractionations. However, what many people have found in rocks older than 2.4 billion years of age, is that some rocks have quite abnormal sulphur isotope ratios, and most people have attributed the presence of mass independent fractionation to atmospheric photochemical reactions, between sulphur dioxide gases from volcanic eruptions and UV light. Since the photochemical reaction will not occur in the presence of an ozone shield, and the ozone shield would form only in an oxygenated atmosphere, this presence of abnormal sulphur isotope ratios, in rocks older than 2.4 billion years of age, has been regarded as our best evidence for reducing atmosphere.

Chris Smith: So does this mean now you can go back, and you will be going back beyond 2.9 billion years, to see how soon this oxygen level seems to begin to rise?

Hiroshi Ohmoto: Yes, we have begun an analysis of rocks of 3.2 billion in age, and also 3.5 billion in age.

Chris Smith: So how does this finding that you've put together, affect the way in which we view the early Earth, in terms of its oxygen status, and therefore, really how life would have responded to that in the early days?

Hiroshi Ohmoto: Most people think that the first types of organisms, which evolved about 3.8 billion years ago were not producing oxygen, and they were methane producing organisms, and that the appearance of cyanobacteria was about 2.5, or 2.7 billion years ago. What our study suggests is the appearance of cyanobacteria, and the evolution of the biosphere, into many different forms of organisms, actually occurred in the very, very early stage of Earth's evolution.

Chris Smith: Penn State University's Hiroshi Ohmoto, on the trail of when the early Earth came by its oxygen rich atmosphere. Finally this week, to the world of social microbes, and the finding that even amoebae like to keep it in the family. Here's Natasha Mehdiabadi. Nature 442, 881–882(24 August 2006)

Natasha Mehdiabadi: We've been working on the social amoeba Dictyostelium purpureum, and it has a fascinating social lifecycle. Most of the time they live as unicellular amoebae in forest soils, and they feed individually on bacteria, and then their social phase is triggered by starvation. What they do is secrete and relay a chemo-attractant, and follow that into aggregations of many thousands of cells, and once they aggregate they can then form a motile slug, which then migrates up through the soil, and then the slug forms a fruiting body.

Chris Smith: So when you say it's a fruiting body, in what way is it a fruiting body? How does it work, and what does it do?

Natasha Mehdiabadi: This fruiting body is actually important for dispersal, and the fruiting body is composed of cells that die, that form a long stalk, and the stalk supports the rest of the cells, which differentiate into spores, which are then dispersed to new locations, so that this lifecycle can start all over again.

Chris Smith: So what did you actually do to answer the question of what's going on when you starve these guys?

Natasha Mehdiabadi: We performed 14 pairwise mixing experiments, between isolates collected at different locations, and then we took one isolate of each pair and labelled it with a fluorescent dye, so we could tell the two isolates apart. Then what we did was plated these isolates in equal proportions, and then allowed them to complete the social lifecycle. And then what we did, once they'd formed fruiting bodies, was assess the proportions of the two isolates in those fruiting bodies, and what we found is that they actually prefer to form fruiting bodies when kin.

Chris Smith: So, I suppose a key question then, must be how does the organism decide who's going to be a spore, and who's going to give up their life and become the stalk?

Natasha Mehdiabadi: Absolutely.

Chris Smith: Have you any, sort of feel for how they might be doing that, and how they can discriminate at such a small level, for those which are closely related, and those that aren't?

Natasha Mehdiabadi: No, that's an excellent question and something that we'd like to find the answer to.

Chris Smith: How are you going to try and solve it?

Natasha Mehdiabadi: So one idea is that there may be differences in cell adhesion, and one might go about investigating this by focusing on cell adhesion genes, and we may be able to do this soon, because the genome is being sequenced for this species.

Chris Smith: Rice University's Natasha Mehdiabadi, who's found that the amoeba Dictyostelium purpureum preferentially unites with its closer relatives, when it comes to forming a fruiting body, presumably so that the organisms that are forced to sacrifice themselves to form the fruiting stalk, still share a high genetic homology with those that actually turn into the spoors.Well, that's it for this week, and thanks very much for listening. Next time we'll be turning up the heat on gamma ray bursts, but in the meantime, if you'd like to follow any of the items in this week's show they're all available from our website at http://www.nature.com/nature and don't forget that Nature is currently exploring a new initiative in open peer review. Certain papers are being made available on a pre-print server, for anyone to comment on before a publication decision is made. In other words, this model depends entirely on the feedback of the community. You can see how it works at http://www.nature.com/nature/peerreview. Production this week was by Derek Thorne, and Anna Lacey, and I'm Chris Smith. Until next week, goodbye. AdvertisementThe Nature Podcast is sponsored by Bio-Rad, at the centre of scientific discovery for over 50 years, and on the web at http://www.discover.biorad.com.