Nature Podcast

This is a transcript of the 25th November edition of the weekly Nature Podcast. Audio files for the current show and archive episodes can be accessed from the Nature Podcast index page (http://www.nature.com/nature/podcast), which also contains details on how to subscribe to the Nature Podcast for FREE, and has troubleshooting top-tips. Send us your feedback to mailto:podcast@nature.com.

Geoff Marsh: This week how to measure something you can't even see.

Christian Marinoni: Really we don't know what we are trying to measure, but at least we want to make sure that our measuring methods are the most precise and accurate as possible.

Kerri Smith: And the origins of an ancient Greek astronomical calculator.

Jo Marchant: The Greeks were using astronomy that came from different places, so we know that they used period relations that were developed by the astronomer priests of the Babylonian world, for example.

Geoff Marsh: Plus how to get sugar out of cells and drug-resistant cancers. This is the Nature Podcast. I am Geoff Marsh.

Kerri Smith: And I am Kerri Smith.

Kerri Smith: Two thousand years ago a Greek mechanic built a machine that could model and predict the workings of the solar system. It's been dubbed the first computer and it's more complex than any other known device for the next thousand years. It was found at the turn of the 20th century in a shipwreck of the island of Antikythera in Greece. Here's researcher Xenophon Moussas of the University of Athens talking about the fragments of the mechanism on the Nature Podcast in 2006.

Xenophon Moussas: In these and the other fragments we can count something like thirty gears which help the astronomers of the 2nd Century BC, we believe now, to calculate the positions of the Sun, the Moon, perhaps to work out the time of eclipses of the Moon and possibly of the Sun as well.

Kerri Smith: This week a feature looks at where the knowledge necessary to make this device came from. Adam Rutherford sat down in the studio with Jo Marchant who wrote about the Antikythera Mechanism. First off, Adam asked Jo what we know about where the device came from or who made it. Published online 24 November 2010 ‌ Nature 468, 496–498 (2010)

Jo Marchant: There are lots of different theories about this. In terms of a physical object this is the only one we have from the ancient world that's completely unique, we don't have anything else for probably a thousand years after this that is complicated and sophisticated as this. But we do have some writings from various people including the Roman author Cicero talking about bronze contrivances that modelled the movements of the Sun, the Moon and the planets. There's one story that Archimedes made one in Syracuse, in Sicily and there's another one that a philosophical Posidonius made one, he lived in Rhodes in the 1st Century BC. There are also some clues from the calendar used on the mechanism itself. The month names are those that were used either northwest Greece or perhaps in Sicily where Archimedes is from, so there are a few hints there as well.

Adam Rutherford: So the basic assumption is that this is Greek, all evidence points to have being a Greek device. But in your feature in this week's Nature, you're indicating that perhaps the intellectual origins of the mechanism might not have been Greek.

Jo Marchant: Yeah, that's right. The Greeks were using astronomy that came from different places. So we know that they used period relations that were developed by the astronomer priests of the Babylonian world, for example. The Babylonians had been looking at the skies for centuries before this because they saw astronomical events as different omens, so they cared very much about being able to predict what was going to happen when. But in terms of the most impressive astronomy in the mechanism that has been seemed to be completely Greek, the pinnacle of Greek astronomical achievement if you like. In particular I am talking about the theory of epicycles. When we look at the Sun, the Moon and the planets from earth, their movement isn't completely constant and the Sun and the Moon appear to speed up and slow down to look at them in the sky. The planets too, this as well, they also seem to change direction and because the Greeks thought that all orbits have to be made of perfect circles, they had theories which involved superimposing different circles on top of each other to account for that motion. And what was thought was that the Antikythera mechanism was using gear wheels riding around on other gear wheels to model that; but there is a new paper out this year in which my feature focuses on which is suggesting that maybe this is not the case at all. In particular, if you take the motion of the Sun, so the gearing for the Sun doesn't survive but what researchers had assumed is that you had some sort of epicyclic gearing, gear wheels riding around on other gear wheels which would give you a pointer that move with varying speed that sped up and slow down and modelled the way that The Sun looks from Earth. But what this new paper shows is that instead of modelling that varying motion using a pointer with varying speed what they've actually done is taken the divisions in the dial that the pointer was moving around so that Sun pointer goes around once in a year and they've shown that the divisions on that zodiac scale were not equally divided. You had a fast zone and you had a slow zone. So it's modelling the Sun speeding up and slowing down using not a varying speed of pointer but using differently spaced divisions.

Adam Rutherford: And such as that mean that it was more accurate than we thought, whether the Greeks weren't right about circular orbits, whether they're actually elliptical, does this new analysis mean that the device is more or less accurate than we previously thought?

Jo Marchant: It's not really a case of more or less accurate. It's just a completely different approach for modelling it. So what we thought was happening is that you have these epicyclic gears modelling the Geometric Theory, modelling the Greeks' Geometric Theory of how the solar system was arranged. This new idea suggests that instead it was a sort of arithmetical approach and this was used by the Babylonians.

Adam Rutherford: So what do these new discoveries tell us about the state of our knowledge of astronomy at this time?

Jo Marchant: Well, this is where we come to, I think, is the most exciting thing about this new paper. So what researchers thought about the Antikythera mechanism was that the Greeks had this really impressive epicyclic theory of how the Sun, the Moon and the planets were working and the Antikythera mechanism is a beautiful realization of that. This epicylic theory has been converted in to these wheels of bronze. What now seems to be the case is that perhaps it wasn't modelling the epicyclic theory, after all it was modelling this more preventive if you like, arithmetic theory. So what the researchers are suggesting is that whoever it was that made the Antikythera mechanism or machines like it, has taken the arithmetic theory and trying to think of ways that they could convert that into gear wheels, how could they model these theories using gear wheels and they came up with the idea of placing smaller gear wheels on to larger ones in epicyclic arrangement. So, instead of the Antikythera Mechanism modelling the Greek theory of astronomy, it's actually what inspired it in the first place.

Kerri Smith: Jo Marchant talking to Adam Rutherford. And that new research paper that Jo mentioned is published in the Journal of the History of Astronomy. The author is Christian Carman.

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Geoff Marsh: Later on in the show we've got some sweet news on cellular sugar transporters. For 20 years researchers have known how sugars get into cells but how do they get out.

Kerri Smith: Before that though we're measuring the unmeasurable.

Geoff Marsh: Since the Big Bang the Universe has been expanding. The effects of gravity should be to slow this expansion over time, but actually the expansion is accelerating and this seems to require something that works to oppose gravity, a force that scientists call dark energy but how do we measure this mysterious stuff?. We know that the geometry of the Universe depends on what it's made off. So by studying this geometry, we might get a handle on dark energy. Christian Marinoni and his team have studied orbiting pairs of distant galaxies and how the light from these has been changed by the geometry of space-time. In this way they provided a new way of measuring dark energy. Geoff Brumfiel called Christian to hear more. Nature 468, 539–541 (25 November 2010)

Christian Marinoni: The safest thing that we can say is that we don't know yet what is causing the Universe to accelerate. We were expecting this expansion to slow down with time and instead it's the contrary.

Geoff Brumfiel: That seems to me like the quite a hard thing to get a hold of them and we sort of live in a three-dimensional world and how can you tell then if physical space is actually spreading apart.

Christian Marinoni: On a human scale you cannot say that because you can't measure that expansion. You cannot see that expansion; see with a telescope or with a machine. Basically you see effect of this expansion on your observables.

Geoff Brumfiel: So at the moment most of the data has come from explosions of distant stars, right?

Christian Marinoni: Sure, you're supposed that there are a class of stars called Supernovae that when explode have a certain throughput of energy per unit time and that power emitted by those stars is constant and so old stars, old supernovae have the same amount of power emitted when they explode, you can make the connection between the flux emitted and flux received and this is called what is the expansion of the space in between the object and the observer.

Geoff Brumfiel: So it's sort of like looking at like a 100-watt light bulb from a distance and since you know it's 100 watts you know how bright it should look.

Christian Marinoni: That's it. And when you measure the flux on your detector, you can see if it is in accordance with the theoretical predictions or you need something else to justify observations.

Geoff Brumfiel: And that's what you've been able to do here. You have a new sort of way of detecting the effects of dark energy, is that right?

Christian Marinoni: Not a new way, because the idea was already there. Alcock and Paczynski first predicted that distant objects don't appear as they are and basically this is due to the fact that we cannot directly measure the intrinsic shape of an object using a ruler for example, but we can only deduce it indirectly by using the light and most specifically the red shift of light waves.

Geoff Brumfiel: And red shift, this is sort of the change of colour as light is further and further away from us, right?

Christian Marinoni: That's it. So the trick is to find the tracks of cosmic objects that have a standard shape in the Universe so that by studying the amplitude of deformation of the images of these objects we can constrain the amount of dark energy in the Universe. What we found is that pairs of galaxies can do the job. Nature doesn't distinguish between left and right, up or down, so you expect pairs of galaxies to be found in any configuration. Instead we predicted that you should observe many more pairs that are aligned along the observer line of sight than expected because of the effect of dark energy. Basically we were able to calculate the degree of this misalignment and we showed that this effect is sensitive to the curvature of space and amount of dark energy.

Geoff Brumfiel: Why does dark energy make these galactic pairs line up?

Christian Marinoni: Basically it's not dark energy that lines up the pairs, dark energy is the effect that's due to the red shift basically the fact that the photons emitted by these pairs of galaxies that arrive to you and give information about the distance of the pairs member and that's where dark energy fits in.

Geoff Brumfiel: I see, so it's just it's changing the sort of apparent distance between the galaxies, where in fact the galaxies are just orbiting each other normally and don't really.

Christian Marinoni: There is no expansion motion in the couple.

Geoff Brumfiel: I have to confess that I am a little bit of dark energy sceptic that actually I kind of think 80% of the Universe we don't even know what it is, like that seems crazy and we just are depending on these distant exploding stars and things to say that there's this huge thing out there I mean, should I be less sceptical now that we have these measurements?

Christian Marinoni: So your scepticism is the scepticism of physicists too. It comes from the fact that really we don't know what we are trying to measure. But at least we want to make sure that our measurements are the most precise and accurate as possible. So, one of the most exciting aspects of the work in my view is that these methods that we have proposed minimize the number of external hypothesis needed in the calculations. These are actually no assumption which cannot be tested from first principles, so it is not only about precision, it's not only about detection but also accuracy matters. And so that's why being sceptical we have to figure out what is the most unbiased way to measure dark energy.

Geoff Marsh: That was Christian Marinoni of the University of Provence in France.

Kerri Smith: And now time for a little splash of 60-second science.

Steve Mirsky: This is Scientific American's 60-second science. I am Steve Mirsky. Got a minute? Look at a map and you can tell right away where New York ends and New Jersey begins but that official border was not a true reflection of how the community is really shaped, because North-eastern Jersey is effectively part of the New York City Metropolitan area and Southwest Jersey is really part of Philadelphia. Researchers from Northwestern University have now mapped country's de facto communities and they did it in an ingenious way using data from the Where's George project. Maybe you've gotten a dollar bill featuring George Washington's mug, it's been stamped to indicate it's in the Where's George system. You can then go to www.wheresgeorge.com and enter the serial number of the bill and you location as well hopefully the next person who gets that bill. The researchers realized that the movement of the dollars tracked by Where's George is the marker for the movement of people and the mobility of people reveals true communities. The research in Public Library of Science One shows that for example the New England States really are a block as is what you might call greater Texas after you've seen the video produced by the researchers, it's at http://www.snipurl.com/georgewash. Thanks for the minute. For Scientific American's 60-second science I am Steve Mirsky.

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Kerri Smith: Coming up shortly the news chat but before that the sugary treat.

Geoff Marsh: In almost every organism from bacteria to plants to humans, sugar is the main source of energy. To make sure every cell has a ready supply, we've evolved ways of storing this vital fuel and moving it around. Almost 20 years ago Wolf Frommer and colleagues worked out how sugars get into cells but how they got out remained a mystery. Now they finally worked it out. They've identified a group of sugar transports that are present in plants and humans and they've called them SWEETS. Charlotte spoke to Wolf and she started by asking him why it's taken so long to find the out transporters. Nature 468, 527–532 (25 November 2010)

Wolf Frommer: Well it's mostly a technical issue, you know, measuring something which goes into a cell is comparatively simple, you can take a cell and grow it on a medium which contains the sugar and if it has the capability to transport the sugar into the cell then it can grow. So that's actually a trick we used about 20 years ago to identify the first plant sucrose transporters, sucrose is just a sugar you put into your coffee which plants use in order to supply to different organs and we used a genetic trick there to get a hand on this where the cells couldn't grow because they didn't have a transporter. If we give it to them, they can grow. So you can easily imagine now something which is being send out of a cell, won't help the cell grow. So it's just a lot more complicated to get a hand on these guys.

Charlotte Stoddart: So what have you done then to get over this problem? How have you identified these elusive transporters?

Wolf Frommer: We've used a trick when recently a Nobel Prize was given to Roger Tsien who developed some very nice technology, so on the one hand he found that there are proteins which are fluorescent, what he also developed which I found even much more exciting is he developed a method where he could measure something remotely inside the cell. So he had essentially a dye based on these fluorescent proteins which changes colour when a certain compound is changing in amount. And we took his trick and applied it to sugars and built a little machine which we can introduce into a cell and when the sugar concentration inside the cell changes, we can monitor that and just by the colour change we can now observe remotely how much sugar is in the cell.

Charlotte Stoddart: So using this trick, you identified some transporters, you found about 20 of them within one plant, what did you learn from this about sugar transport?

Wolf Frommer: One of the most exciting findings was that bacteria basically become burglars, enter a plant and dine and dash essentially. What they do is something very, very simple, they have a protein which they inject and this protein switches ON this transporters which are probably normally required for feeding the pollen, they now switch them ON in a leaf, just in the area where they're sitting and so they can now feed themselves and then what was even more surprising was but humans also have also homologues of these transporters, which have never been characterized.

Charlotte Stoddart: And you've named these transporters collectively the SWEETS transporters which are a rather apt name, and you say in your paper that knowing more about these SWEETS Transporters is going to help us deal with pests on crop plants. It's going to help us understand pollen nutrition, nectar production, even carbon sequestration, it sounds like there are loads of studies you could go on and do next. So what are you going to look at next?

Wolf Frommer: We will try to study these processes which you mentioned in the plant. So we will try to understand what all these 20 different variants which are specialized in special organs, like the nectaries or the feeding structure for the pollen or other tissues, what they are really doing. We will actually try to find small molecules, drugs which can inhibit these transporters, because the idea of course that if you inhibit these transporters then the pathogen cannot infect the plant anymore.

Charlotte Stoddart: You must have been very excited when you found these transporters, given that it's been, you know, so long since we found the ones that take the sugars into cells?

Wolf Frommer: Absolutely, we were totally excited when we found them, when you do these studies, you'll never know whether you can get there 20 years ago, we were very excited when we found the import transporter of the vascular tissue for the veins for sugars and plants and we were at least as excited now that 20 years later we could identify the counterparts.

Geoff Marsh: Wolf Frommer talking to Charlotte.

Kerri Smith: And now for the headlines.

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Kerri Smith: The tumour suppressing gene p53 may only spring into action once cancer cells become aggressive report two papers this week. The study suggests that early stage tumours don't trigger to gene to exert its anti-cancer effects which could limit its usefulness as a way to eradicate cancer. Two separate teams one in Boston and one in California studied mice with lung cancer to see when the p53 gene was switched on. They both found that restoring p53 led aggressive cancers to regress, but left others untouched. This is probably because the body's tumour surveillance mechanisms don't recognize early stage tumours and activate their defences. Nature 468, 567–571 (25 November 2010); Nature 468, 572–575 (25 November 2010)

Geoff Marsh: A few months ago we told you about a promising new drug that could shrink some skin cancer tumours by about 30%. The drug called PLX4O32 blocks the mutated form of a protein involving cancer cell growth. However, research since then has found that the drugs effects are temporary and cancer cells become resistant to it over time. Two articles in this week's Nature detail how cancer cells short circuit the drug's effect. The researchers found that three other proteins that drive cell growth are over expressed in resistant cells. This indicates that the new drug may only be an effective therapy in combination with other drugs that can compensate for the resistance. Nature advance online publication 24 November 2010; Nature advance online publication 24 November 2010

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Kerri Smith: Finally this week it's not the Nature Podcast without the Nature Podcast news chat. Richard Van Noorden, news gatherer extraordinaire is here to guide us through the news this week. Hello.

Richard Van Noorden: Hello Kerri.

Kerri Smith: Now first, give us an update on the cholera situation in Haiti.

Richard Van Noorden: Yes, some epidemiologists are warning that the cholera epidemic that has hit Haiti means that the country could face more than half a million cases over the coming year. So far we've had roughly 20,000 cases and 1100 deaths since this outbreak was first detected in October. But our news piece this week really focuses on how to track and treat cholera which is proving increasingly difficult as riots and civilian unrest are gripping Haiti ahead of elections.

Kerri Smith: So it's not necessarily a problem with the science of tracking these diseases, but it's the political situation that's making things problematic?

Richard Van Noorden: Exactly. It's the problem of the situation Haiti and for example, cholera is eminently treatable. You just need to be promptly rehydrated with oral rehydration. In that case mortality in a cholera epidemic is typically below 1%; but in Haiti we're having far higher death rates obviously, in a country that's ill prepared and has suffered an earthquake in January. At the beginning of the outbreak, mortality was 9% and it's fallen to some 4 to 6% over the past few weeks, but with the riots this gain is really starting to be wiped out.

Kerri Smith: Do the epidemiologists in question make any predictions about where this outbreak is going?

Richard Van Noorden: Well, last week the Pan American Health Organization which is just the regional office of the World Health Organization said 200,000 more cases could be expected over the next year, but Jon Andrus who is the Deputy Director says more recent estimate suggest more than 500,000 and this isn't just doom and gloom forecasting, they actually have to know the numbers to make sure there's enough supplies and there's enough staff on hand and that they are ahead of the game. Another problem is that the Haiti outbreak might spread into neighbouring countries like the Dominican Republic and experts are very mindful of how a 1991-outbreak in Peru then led to a whole suite of entrenched cholera outbreaks across the Americas except in the Caribbean. So understood they've put the whole hemisphere on alert.

Kerri Smith: So what would help to contain this outbreak, I mean, vaccinations is one possibility I suppose?

Richard Van Noorden: Yeah, actually health agencies did contemplate using vaccines to try and stop or curb this outbreak but in fact there isn't any few hundred thousand doses of vaccine available, anyone cholera vaccine approved by the WHO and it's far too expensive to be used in developing world. Millions were needed and even if there was sufficient vaccine others are currently going through the WHO's approvals process. It might have a little impact because the logistics would have been very daunting and so vaccines would not be a panacea and the main treatment options remain getting to people, rehydrating them and hoping that these riots which are causing road blocks and stopping deliveries of supplies, well hoping that these riots die down, but that looks unlikely.

Kerri Smith: Okay, well moving on to our second story and this is about being able to tell someone's age from a blood sample.

Richard Van Noorden: Yes apparently blood stains found at crime scenes could give an indication of a person's age now this is doubly unusual because normally when you collect something from a crime scene you compare that with a database of DNA information but this is about building a physical profile of a person on the basis of their DNA alone, obviously we know you can tell whether someone has blue or brown eyes from the DNA alone. In a paper published in Current Biology, researchers in the Netherlands say there's a genetic signature in your DNA for your age in a type of white blood cell known as the T-cell.

Kerri Smith: So how does this method work?

Richard Van Noorden: Well the way it works is that the organ that pumps out these T-cells the thymus is gradually replaced with fat tissue as people age and every time a new T-cell matures in the thymus it rearranges its DNA so that it can create a receptor that recognizes foreign molecules, pathogens and this leaves a tell-tale loop of excised DNA behind. So that means that because these loops are only on new T-cells you can look at the levels of a particular loop sequence in all the T-cells in blood and then if there are lots of them you can tell there are a lots of new T-cells and if there aren't very many, well not many new T-cells have been churned out, your thymus is obviously older and that all that correlates with age. Now there's a bit of a problem, does this T-cell loop correlate with age in other ethnic groups than the Dutch volunteers they tried in this sample and then what happens if you have some sort of condition that perturbs T-cells like HIV or diabetes, does that mean that the technique is limited?

Kerri Smith: I mean how useful is that? Is this is a piece of knowledge we're often missing when we look at a crime scene and we can find blood samples.

Richard Van Noorden: Well normally we would determine someone's age by their bones, or their teeth but you don't often have that in a crime scene. No there is no real way to do other than other evidence. So this is the first time that it can be done, but it's not that useful because it tells you to within plus or minus nine years. So it's not really going to break open, cold cases or anything like that, but it could be used to distinguish young from old people.

Kerri Smith: Is it likely that this method will be put into practice anytime soon?

Richard Van Noorden: Well, because that the limitations, possible limitations with other ethnic groups that I mentioned there, actually need to firm up this before they can put into practice and they'll never have the technique on its own. It will have to be combined with other sources of evidence to rule any suspects in or out of the crime scene.

Kerri Smith: Okay thanks Richard. You surely know where to find more, http://www.nature.com/news.

Geoff Marsh: And that brings another show to a close, thanks for tuning in. Come back next week when we will be trying to reverse the effect of aging and rounding up some recent progress in piecing together protein structure. I am Geoff Marsh.

Kerri Smith: And I'm Kerri Smith, forever young.