Nature Podcast

This is a transcript of the 9th August 2012 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.

Kerri Smith: This week, cancer stem cells show themselves.

Carla Kim: These papers may convince some people that indeed this is a question that they should re-examine.

Geoff Brumfiel: And they just landed a rover on Mars, but our NASA's most celebrated project is too big to fail.

Daniel Baker: Ultimately it comes down to the huge battle star Galactica kind of an approach, too big to fail kind of thing.

Kerri Smith: Plus get into grips with the world's ground water reserves. This is the Nature Podcast. I'm Kerri Smith.

Geoff Brumfiel: And I'm Geoff Brumfiel.(Cheering crowds)

Geoff Brumfiel: Unless you actually live on Mars, you know that NASA just managed to land a rover there. In a rare opportunity for the Nature Podcast, we actually have someone on the scene in Pasadena and we're talking to him live via satellite uplink. It's Ivan Semeniuk, our head of US correspondents. Ivan so you have been there the entire time as this rover has entered the Martian atmosphere and landed on the surface and have you been getting a lot of sleep? Nature 488, 129 (09 August 2012)

Ivan Semeniuk: Almost no sleep at all, Geoff, but you know, that's part of the course for the journalists as well as for the scientists who are now on Mars time and going in shift around the clock with the rover.

Geoff Brumfiel: So, this landing, I have to say, it was very exciting for me, I actually got up at 6 o'clock in the morning in London to watch it because the entry descent and landing phase, the EDL as they call it, just seemed crazy to me, it's been crazy that they were actually going to do this thing. Tell us a little bit about how that unfolded

Ivan Semeniuk: It was an incredible system and something that had not yet been tried before on Mars. It was devised in order to bring down a much heavier payload than before. The mass of the rover is about 900 kilos. So, including the parachute and this descent stage firing rockets and then hovering above the surface and then cables gradually lowering the rover down to the ground, it just seemed like there were so many things that could go wrong, you know, it's been described as a kind of Rube Goldberg contraption.

Geoff Brumfiel: Yeah, I have to say when I was watching it over here in London, I mean, I was basically reduced to like a 13-year-old school girl giddy with excitement when it was finally touchdown and they started yelling it's the wheels, it's the wheels. So, how was the atmosphere actually like in the Jet Propulsion Laboratory?

Ivan Semeniuk: Well, it was just jubilant. I mean, I've been to every Mars landing since Pathfinder, since the first tiny little rover started this process in 1997 and you know, it can be quite scary because just on a dime it can turn and a celebration can suddenly become a funeral. This really was picture perfect all the way. There was I think the key thing was that there was a continuous signal with the rover all the way down and that was relayed by the Mars Odyssey Orbiter so now that there's so much hardware in orbit around Mars, it's possible, you know, to hear the Lander going down. Also the MRO Orbiter with its giant cameras snapped a picture of the rover on its parachute drifting down, so the thing was observed and listened from all angles as it went down and there's tons of information about this EDL.

Geoff Brumfiel: Now most of the attention to this point has been on the rover's actual landing on Mars, the fact that it appears to have gone incredibly smoothly, but of course what we're excited about here at Nature is the science this thing can do and I guess, you've been talking one of the scientists about what this rover is actually going to do, now that it's on the Martian surface.

Ivan Semeniuk: That's right. So not even a day after the landing, I had a great conversation with Paul Mahaffy, one of the 400 scientists working on this mission, but he's got a special role, he's the principal investigator for SAM which is the Sample Analysis at Mars and I wanted to talk to him in particular, you know because this is going to be some of the earliest and potentially, some of the most exciting science to come out of the Curiosity. SAM is the instrument on board that analyzes soil samples and also it can analyze atmospheric samples. So I spoke with Paul Mahaffy about what they hope to learn and here's his response.

Paul Mahaffy: The very first science measurements we get in a few weeks really will be a sample of the atmosphere that we ingest into SAM and we'll look at that with two of our instruments, with a tuneable laser spectrometer and with a mass spectrometer.

Ivan Semeniuk: Now, let's talk about the surface and the soil as well. Once SAM starts to get pieces of Mars or bits of the soil, what will it be looking for?

Paul Mahaffy: With the solid samples, we analyze, we're really looking in the first place for volatiles, for gases, released from solids as we heat them up, the profile of how those volatiles get released tells us something about the minerals that's really, really interesting. The other thing we do is look for heavy versus light elements in those minerals, that's called isotopes. So that will tell us something about how the atmosphere changed over time, but the third thing we're really looking for is organic compounds that might really help us get a handle on the conditions, the habitability potential of early Mars. We have no idea if we'll find a wealth of organic compounds or not, but we think that there's really a good chance that we'll see some organic compounds. If we start seeing a diversity in organic compounds, not just one or two but many, then we're really onto something because what we will look for then is patterns in complexity because on earth for example, the patterns that show up in structure and types of organic compounds that we find in rocks or in soils are really formed by life processes. So if we find a diversity of organic compounds, we'll just be really interested in looking for those patterns.

Ivan Semeniuk: Well, I guess that brings us to the 64 thousand dollar question, which is if there was life on Mars, at some point in the past, would Curiosity be able to tell us that?

Paul Mahaffy: What we're really hoping as a first step with Curiosity is in terms of our search for organics can we find spots where organics are preserved, the very first order question, that's one reason we're going to Gale because these clay layers may be a good preservation environment for ancient organics. It would be probably way too bold to say that if we find a wealth of organics we'll be able to understand whether ancient life existed on Mars but it certainly would be a good step in that direction.

Ivan Semeniuk: Well Paul Mahaffy, thank you so much for telling us about it and good luck with your mission.

Paul Mahaffy: Thank you very much. We're really excited.

Geoff Brumfiel: So, Ivan, this thing is now sitting on the Martian surface, what comes next?

Ivan Semeniuk: So, once they've started to check out all the science instruments and get that first whiff of the atmosphere that Paul Mahaffy was talking about, you know, we can now start to, you know, look at the movement phase of the mission. You know, It'll start to talk its first tentative rolls or steps on the surface, then there's going to be this ongoing debate about where do we go, where do we go next, where do we go next and John Grotzinger who's the Science Lead for the entire mission described it as finding a bunch of little pearls, interesting little sites nearby that they can string together as they start to work their way towards their larger goals.

Geoff Brumfiel: Thanks Ivan and there's more about Curiosity on Nature's web site, http://www.nature.com/news.

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Geoff Brumfiel: Now NASA specializes big world class projects like landing a rover on Mars, but are they undercutting the agency's future? In a commentary piece this week, Dan Baker of the University of Colorado at Boulder argues that NASA's focus on multibillion dollar rovers and space telescopes is coming at the cost of university programs that will supply the next generation of scientists. Nature 488, 27-28 (02 August 2012)

Geoff Brumfiel: From your perspective, it doesn't really matter if the mission was successful or not, there's still a big problem at NASA right,

Daniel Baker: Yeah, so of course it matters a great deal as far as the future of the space program in US but you're absolutely right. The point that I've been trying to make is that these extremely large missions, complex missions, and often over budget missions are eating so much of the resources for an agency like NASA, especially in these times of highly constrained overall federal budgets. It's crucial that we have the right balance, the right mix of different kind of mission sizes.

Geoff Brumfiel: Well let's talk a little about Curiosity and some of the other missions at NASA that are going on right now. I mean, Curiosity itself is a 2.5 billion dollar rover mission. What is going on with these mega missions? Why are they so much over budget? What is, sort of, driving them do you think?

Daniel Baker: Well, your question is a great one. What is driving cost spills,, cost over runs seems to be the order of the day, probably one of the principal drivers is aversion to risk that if you put so much money into a program, you want to try to assure that it's not going to fail and then you start to add more levels of quality assurance and more paperwork and more people and pretty soon you start ratcheting up to these extraordinarily high class. Ultimately it comes down to this huge battle star Galactica kind of an approach, too big to fail kind of thing.

Geoff Brumfiel: Right, so I mean, this is a big central point of your article is that these NASA centres, by NASA centres we mean, the jet propulsion laboratory or the Goddard Spaceflight Centre. These large centres have really taken over space science in NASA to a degree right?

Daniel Baker: That's correct. And of course, I appreciate the role and I'm very supportive of some of the roles that the NASA Centres have played, they're absolutely indispensable in this mix, but I also believe that if one doesn't put constraints on programs, then they will grow without bound and that, especially in these times, is an insupportable thing. It drives out all other kinds of approaches, small-end missions; it drives out the principal investigator led kind of programs that have been the bread and butter of university research groups.

Geoff Brumfiel: So what can universities bring to the table here?

Daniel Baker: First and foremost, this is where future space scientists, space engineers, space managers are really trained, so without a vigorous program, where you can get hands-on education and training, you really will not be producing a viable next generation, but over and above that, universities also tend to be much more nimble and much more flexible, much more adaptable than large bureaucratic organizations.

Geoff Brumfiel: So what would then NASA of your future look like, I mean, what do you think NASA should look like?

Daniel Baker: I believe and I want to emphasize strongly that I think when it comes to science and when it comes to exploration, NASA needs a spectrum of different capabilities. It needs the ability to build large complex, the so called flagship missions on occasion to go do the most challenging things that a nation or the world can conceive of, but it also needs this smaller end of the spectrum, it needs vibrancy. So the NASA that I would envision would be one that has thoughtfully examined all of the different elements from the largest missions down to the smallest missions.

Geoff Brumfiel: Do you see any signs of NASA doing any of this?

Daniel Baker: There often are thoughts about this, right now I think there's lot of paralysis rather than action and I believe that part of the reason for writing a commentary is to try to break some things loose and start to get some action.

Geoff Brumfiel: That was Dan Baker of the University of Colorado at Boulder.

Kerri Smith: Coming up in a moment, three new studies go hunting for cells that build tumours, but before that the research highlights with Daniel Cressey in London.

Dan Cressey: Living on our skin are millions of bacteria. It turns out that we need these good microbes to help us fight the bad ones. Researchers studied mice with microbes on their skin and compared them with germ free mice raised in aseptic conditions. They found that immune cells called T-cells did not function as well in the germ-free mice. When infected with a skin parasite, the germ free animals had a large number of parasites in their skin lesions from the animals with skin bacteria. Previous researches show that bacteria in our guts are important for intestinal immunity and now it seems like the same goes for the bacteria on our skin. You can find the study in the Journal Science. Nature 488, 8 (02 August 2012)Hungry bats can tune into the sound of flies mating to pick out tiny prey that would otherwise pass them by. Researchers in Germany analyzed videos of Natterer's bats feeding on flies in a cowshed. Thousands of flies walked across the ceiling without being attacked, but flights that were copulating were attacked 5.3% of the time and bats also attacked speakers playing back the distinctive noise produced by copulating flies. This is the first mechanism to be identified that supports theories that copulation can leave animals more vulnerable to attack. The study is published in Current Biology. Nature 488, 132-133 (09 August 2012)

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Geoff Brumfiel: Most of the fresh water we depend on for drinking and agriculture since underground in huge reservoirs but these reserves are under threat from contamination and overuse. Tom Gleeson at McGill University in Canada and his colleagues worked across the globe at how quickly water flows into underground reservoirs versus how much of it is being used up by people. They wanted to figure out if water is being used sustainable and if not where the biggest problems exist. Natasha Gilbert talked to Tom. Nature 488, 197-200 (09 August 2012)

Tom Gleeson: Both ground water and surface water come from precipitation. Surface water is the precipitation that just stays on the surface of the earth as rivers, lakes and wetlands, while ground water is precipitation as it goes into the ground and goes into what we could call aquifers, these are the underground reservoirs. So actually 99% of the fresh unfrozen water on planet earth is ground water, so it's a huge reservoir that planet earth has and that can buffer us as a species and as a planet if we manage it properly. And groundwater is under threat because it is being overused and contaminated in a number of areas and we really focus on the overuse.

Natasha Gilbert: So, you have calculated how quickly supplies are being used up. Can you explain how you calculated that and what you found?

Tom Gleeson: Though unfortunately we don't really know how much groundwater there is on planet earth in many of these aquifers, what we really looked at is the ratio of how quickly ground water enters the aquifers or flows into the aquifers versus how much groundwater is being used by humans and how much should be left for ecosystems. So, we used a global water model and we also used global compilation of groundwater use in different regions and compared those two data sets. And what we found is that humans are overusing groundwater in a number of regions. In Asia and North America they are crucial for growing food. In fact over a quarter of the population of the world live in regions where groundwater is being overused.

Natasha Gilbert: My understanding of groundwater is that they, it's very difficult for them to be renewed and refreshed, so basically once you have used it up that's essentially it.

Tom Gleeson: That is how some people look at groundwater. Groundwater really is a renewable resource so every year continually in lots of regions, there's precipitation and that slowly percolates into the ground and that becomes groundwater, so it is a renewable resource unlike oil, even now it's being used as a non-renewable resource in a number of regions like Saudi Arabia, United States and India and China as well but it can be used as a renewable resource if we manage it properly in most regions.

Natasha Gilbert: So, you mentioned the US and Asia is two places that you found where this groundwater supplies are not being used sustainably. What can be done to help ensure that they are being used sustainably and how will, you know, the kind of calculations that you've done help to illustrate that?

Tom Gleeson: Our analysis is very large scale. We were looking at the whole globe so if the details of specific regions or specific aquifers zone are not really examined but what we show is where groundwater is being used sustainably and where it is not being used sustainably and that could inform management practices. So it could affect how much water or groundwater is being used for irrigation or allocated for irrigation and also show which regions of the world the groundwater could be used sustainably to grow more food, for example.

Natasha Gilbert: And presumably this use is going to increase over time, I mean what kind of suggestions would you make in terms of improving the use of groundwater and making it more sustainable?

Tom Gleeson: So, a number of shifts or changes in agricultural use are possible. We could try to increase what's called irrigation efficiency. So that increase the crop per groundwater drop that we grow or we could shift to different types of food, less water intensive food like a vegetarian diet is much less water intensive than a meat-based diet. And we could grow food in regions where water is naturally more abundant rather than in regions that are, where water is scarce or water is very slowly renewed.

Natasha Gilbert: And if we didn't use it properly when would we use it up?

Tom Gleeson: Well, the problem is we don't really know exactly the volume of groundwater stored in most of the aquifers. So, even though we know now the rate that it is being drawn down or the rate of depletion as it is called and we don't know the volume very precisely in most aquifers, so we can't tell the lifespan of the aquifers or how long we have until we run out.

Kerri Smith: That was Tom Gleeson.

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Kerri Smith: If we could tell which cells were responsible for the growth of tumours we could take out those cells and nip tumours in the bud. Many studies suggest that there is a population of self renewing cells that a root of any tumour - cancer stem cells. These cells might be the master builders of tumours. Here's Carla Kim who studies stem cells at Boston Childrens Hospital to explain the theory. Nature (2012); Nature (2012)

Carla Kim: Within tumours there is a rare percentage of cells that could re-grow a tumour and that might be the explanation for why tumours can reoccur after treatment and that that might be explained because they have some similarity of stem cells.

Kerri Smith: Stem cells can self-renew and turn into any other type of cell but are cancer stem cells real? It hasn't been obvious to explain why, here's Cédric Blanpain from the Free University of Brussels. In a new study, his team investigate the existence of these cells.

Cédric Blanpain: The model of cancer stem cells has been controversial for several reasons. One of the reasons is the experimental assay to assess their existence and what is the assay that exists in the past is the transplantation to grafting of tumour cells into a very severely immunodeficient man and so in this circumstance somehow you test what the cells can do that you don't necessarily test what the cells naturally do in their natural environment.

Kerri Smith: So`past experiments could be accused of being a bit artificial, but this week's three different studies rectify that, one by Blanpain's group looks at skin cancer and two other papers by groups based in Texas and the Netherlands look at the brain and the gut. I asked Carla, who wasn't involved in any of the studies herself, about the methods they had used.

Carla Kim: There are important differences between each groups and assays, but essentially what they've been able to do is genetically tag certain cells within the tumours, they can then make interpretation about which cells in the larger tumour may have been derived from a single cell or from multiple cell population and the importance of all of this is that this was done without removing the cells from their normal tumour environment.

Kerri Smith: Each team found a population of cells that looked suspiciously stem like.

Carla Kim: These papers may perhaps convince some people who didn't think that there was solid evidence for cancer stem cells but indeed this is a question that they should re-examine and more solid evidence that this hypothesis is true.

Kerri Smith: In fact it turns out cancer stem cells look a lot like normal stem cells. Blanpain studying skin tumours was surprised to find that tumours grew in much the same way as normal skin with the same hierarchy of cells making tissue.

Cédric Blanpain: We found that somehow the hierarchy that exist in this early tumour core resemble very much to the normal hierarchy that can lead to the tissue renewal. It's simply the speed of per cycle of the stem cell and the committed progenitor that are very different in tumour than in the normal tissue, but somehow the principle that drives to grow is very similar.

Kerri Smith: Which could be a problem for trying to target these cells directly.Inte1rviewee - Carla KimOne of the biggest questions in this cancer stem cell field is then, if there are similarities between a cancer stem cell and normal tissue stem cell, then if we are working to develop therapies to target a cancer stem cell, we need to also make sure that we're not affecting the normal tissue stem cell. But what this really points out is the future study which many of us are actively engaged in is trying to understand now what exact molecular mechanisms are different in the normal stem cell and than that early cancer stem cell.

Kerri Smith: There are other glimpses of hope for treatment now that cancer stem cells are on a firmer footing. In the study on brain tumours by the Texas team, the stem like cells were labelled and then a drug was targeted towards them inactivating them. The drug managed to shrink the tumour in conjunction with chemotherapy and Blanpain says knowing what they now know about the lifestyle of these cells, for example that they divide twice a day, could help clinicians refine how they administered treatments. After all though no two tumours are the same. The last word from Carla Kim.

Carla Kim: In my mind we need to ask this question with every type of tumour individually and it doesn't necessarily mean from these three papers that every tumour type will have a cancer stem cell.

Kerri Smith: Carla Kim and before her Cedric Blanpain. Find two of those papers by Blanpain and Parada on Nature's website and the other by Clevers at http://www.sciencemag.org/.

Geoff Brumfiel: That's all we have got time for. Join us next week. I am Geoff Brumfiel.

Kerri Smith: And I am Kerri Smith

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