Nature Podcast

This is a transcript of the 28th October edition of the weekly Nature Podcast. Audio files for the current show and archive episodes can be accessed from the Nature Podcast index page (http://www.nature.com/nature/podcast), which also contains details on how to subscribe to the Nature Podcast for FREE, and has troubleshooting top-tips. Send us your feedback to mailto:podcast@nature.com.

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Charlotte Stoddart: Coming up: controlling images with your mind.

Moran Cerf: So we tell them, now, actually we are going to show something remarkable, you can move things on the screen with your thoughts and they sit there and they just thought thinking and just by doing so things move on the screen.

Geoff Marsh: And: girl or boy? The evolution of sex determination.

Ido Pen: We were looking at a sort of snow skink, which is a small lizard that is there is on Tasmania. This species is quite unique in the sense that within the same species you have the coexistence of this different sex determinations.

Charlotte Stoddart: Plus the first results from the thousands genome project. This is the Nature podcast and I am Charlotte Stoddart.

Geoff Marsh: And I am Geoff Marsh.

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Geoff Marsh: Within the vertebrates, there are loads of different types of sex determination, the process by which an embryo is sent down the path of becoming a male or a female. For example, sex can be determined genetically as it is in humans or by the temperature of the embryo, but exactly what causes this variety to evolve has puzzled biologists for a long time. Ido Pen and colleagues tackled this question by studying the spotted snow skink, a small lizard from Tasmania with peculiar sex determination. Nature advance online publication 27 October 2010

Ido Pen: This species is quite unique in the sense that within the same species you have the coexistence of these different sex determining systems, so you have the population of lizards in the mountains that has genetic sex determination and you have a population living near the coast that has temperature dependent sex determination, so this would be a very good species to test series about the evolution of one system towards the other.

Geoff Marsh: In the wild you've got these two different groups of these skinks so how do they spawn out for the sex ratios within these two different groups?

Ido Pen: Well, now the main difference between the lowland and highland population is of course is, first of all the average temperature. The average temperature is lower of course in highlands compared to the lowlands but also between-year fluctuations in temperature were much bigger in the highland compared to the lowland. And there's an important theory that try to explain the evolution of temperature dependent sex determination which acts as the fluctuations of between years in temperature are very large, this would select against temperature dependent sex determination and the reason is that you've got big fluctuations between years then you'll also get years with either a lot of females being born that year or a lot of males being born that year and that there's selection against that.

Geoff Marsh: Right, so I mean that sounds intuitive, how did you go about proving that that's actually the reason that these different sex determination systems arose in the first place?

Ido Pen: So what we did was we made a theoretical evolutionary model to put as much of the biology of the two populations as we could find into the model and to see what kind of system would evolve and the data that we used were on the one hand climatological data where 02.58 you would yearly within season and between seasons temperatures of both the highland and the lowland population and we also managed to calculate how temperature has an effect on the reproductive success of females in both the highland and lowland population. This came from data collected during decades on these two populations.

Geoff Marsh: So you made the model, you put in the computer and you pressed go, how well that it fit your data?

Ido Pen: Well it fit our data remarkably well. We saw that in the simulations for the highland populations whereas there's genetic sex determination, the model also predicted genetic sex determination and for the lowland population where we have temperature-dependent sex determination, the model predicted temperature-dependent sex determination and this was a big surprise, you know, we sort of hoped, of course, that something like that would come out but we were surprised that actually it came out.

Geoff Marsh: Okay, so this model that you've come up with is a neat fit for a snow skink but I mean you said you thought that the snow skink is a bit of an outlaw within the reptiles, you know it gives birth to live young not eggs. It has both of these systems. Do we think that these results translate to vertebrate groups as a whole or to reptiles as a whole?

Ido Pen: Well they might very well because a variety of species have been investigated into a lot of detail. It could be that there are many more species where there is coexistence of different sex determining systems. It generally indicates that seasonal effects have strong effect on fitness, the young reproductive says in many species and that's exactly what's going on in this species. If you have temperature-dependent sex determination, then one sex is all produced when it is hot and the other sex is produced when it is cold and often it is the case in females, temperature has a bigger effect and fitness than on males. This could select for temperature-dependent sex determination, unless there are big fluctuations in temperature between years because this would select against sex determination and this is the only species that we know where we have both data on the effects of temperature on fitness and reproductive zest and where we have good data on the fluctuations in temperature between years.

Geoff Marsh: Ido Pen of the University of Groningen.

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Geoff Marsh: Coming up shortly is the headlines in which we will be tackling at ancient monkey puzzle and weighing a neutron star, but before that the latest on a rather grand project in genomics.

Charlotte Stoddart: This year marks a decade since the draft sequences of the human genome were published. Back then sequencing just one genome required huge effort but in the last 10 years, sequencing technology has improved dramatically and today it's hard to keep track of the number of human genomes being sequenced. This week sees the publication of results from the pilot phase of the 1000-genomes project and to tell us about it, Nature's Genetics Editor Magdalena Skipper joins me in the studio. So first of all Magdalena, what is the 1000-genomes project? Nature 467, 1061–1073 (28 October 2010), Nature 467, 1050–1051 (28 October 2010), Nature 467, 1026–1027 (2010)

Magdalena Skipper: The aim of the project is really to characterize the variation in the human genome. In fact, specifically the project states that it will at its completion characterize 95% of variation in any single individual and the variation that the project is particularly interested in would be present in a population in a frequency of down to 1%.

Charlotte Stoddart: Now we've heard on the podcast before about the HapMap project, which also aims to characterize human genetic variation, so how is this different from that?

Magdalena Skipper: Probably in the most basic way is the depth of characterization of the variation. The HapMap project characterized variation in the human genome but importantly because of the technology that this project used which was micro-array technology, it could only really access variants that are down to 5% frequency in a population. What the 1000-genomes project aims to do because it uses sequencing, it can essentially look at much less frequent variation so they will in fact catalog and describe variation that goes down to 1% frequency in a population.

Charlotte Stoddart: And it's called the thousand genomes project, I mean is it actually looking at 1000 genomes?

Magdalena Skipper: In fact it is not. I rather suspect that it was named 1000-genomes project because it just sounds so lovely and rolls off the tongue, ultimately some two and a half thousand genomes will be sequenced so thousand genomes is a name.

Charlotte Stoddart: Right now they're announcing the results of the pilot phase of this project which was testing three different genome sequencing strategies, what were those three approaches?

Magdalena Skipper: The first phase used the so-called low coverage approach. So here just under 200 individuals were taken to be sequenced 2X coverage. What this essentially means is that any part of the genome has been sequenced twice. This low coverage is specifically designed for economic reasons. Sequencing is still very expensive, especially if you sequence a whole genome, so then the question then the thousand genomes project was trying to address was how much information can be got out of this low sequence coverage, using a number of individuals and then combining the information together. Another aspect of the pilot project involves specifically deep sequencing, this is where the genome was sequenced and around 50 times on average over a family tree. One of the things that geneticists are interested in is the germ line mutation rate. In other words, the rate at which mutations arise from generation to generation and by comparing DNA sequence between parents and children, you can infer that mutation rate directly. And the third part of this pilot phase involved a deep sequencing of coding regions.

Charlotte Stoddart: So what have we learned then from this early phase of the project?

Magdalena Skipper: Probably one of the most important take home messages from the point of view of technology and analysis is that indeed we can use this low coverage sequencing for a number of individuals in order to infer variation and at quite precise level.

Charlotte Stoddart: So that's all we've learnt about the sequencing approach but have we learned anything about human variation itself at this early stage?

Magdalena Skipper: Absolutely, so this sequence data, this low coverage sequence data across the genomes has been available to the community and has already informed many genome wide association studies which aim to associate particular genetic variants with particular phenotypes. Several of these studies have already been published. This particular study, in addition, concludes that each one of us carries about 250 to 300 loss of function variants in already known genes. This is something that geneticists refer to as genetic load. The reason why we are not suffering from any genetic disease is because of either redundancy but mainly because these variants are recessive, in other words there would have to be two copies of them in any one individual to succumb to disease.

Charlotte Stoddart: What's the next phase of the project then? And when can we expect some more results?

Magdalena Skipper: One of the things that the project is very interested in is providing an in-depth catalog of variation for different human populations across the globe, so while the pilot phase was limited to a small number of populations, the full phase of the project will be expanded to cover populations from across all of the continents and the number of genomes that will be sequenced will be dramatically increased.

Charlotte Stoddart: Okay Magdalena. Thank you very much.

Geoff Marsh: Very shortly we will be finding out how patients can control images on a computer screen with their thoughts. But first we've just time for a round of the best of the rest in nature.

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Geoff Marsh: Where and when did the anthropoids, the group including monkeys, apes and humans originate? Some scientists think they came from Africa while others favor Asia. A crutch of fossils on earth in Central Libya and representing several new species supports an Asian birthplace. The team that found the fossils suggests a mass monkey migration from Asia to Africa around 40 million years ago. They think several different species probably colonized Africa around this time along with rodents and other mammals. Nature 467, 1095–1098 (28 October 2010)

Charlotte Stoddart: Researchers have weighed a neutron star. The remains of a normal star that has died. The neutron star was orbiting a companion star and it was also spinning which caused it to send out millisecond pulses of radio waves. When the neutron star passed behind its companion, the gravitational field distorted the radio signal. The distortion was proportionate to the mass of both stars and this allowed astronomers to estimate the neutron star's mass at about twice that of our sun. Some theories predict that exotic forms of matter might lurk inside neutron stars but this mass measurement suggests that there's nothing more than neutrons. Nature 467, 1081–1083 (28 October 2010),Nature 467, 1057–1058 (28 October 2010)

Geoff Marsh: An 8-year biodiversity experiment shows the importance of plant diversity for a healthy ecosystem. Most studies focus on the effect of reducing biodiversity within just one level of the food chain, not very realistic. This new study published in Nature looks at the effect of plant diversity at every level of a complex food web. The researchers sowed different numbers of plant species in almost a 100 different plots. They found that diversity on this bottom rung of the food chain had effects right away through the food web, whereas some had expected many of the effects to be due to predators at the top of the chain. Nature advance online publication 27 October 2010

Charlotte Stoddart: Sitting here in the dark studio in London, it's easy to conjure up images from my recent sunny weekend on the beach....(Voice) Char....lottte........(sound of waves splashing)Oh! examples of this show us this internal thoughts and plans can win out over the external environment but how, that's what a team based in California has been finding out via a brain machine interface. They worked with a rare set of patients who had electrodes implanted in their brains in preparation for surgery. They showed them various images and measured the responses of individual neurons. The patients could then learn to fade these images in or out by regulating the behavior of those neurons. Kerri Smith chatted to lead author Moran Cerf and first asked him about the use of brain machine linkups. Nature 467, 1104–1108 (28 October 2010)

Moran Cerf: The idea that if you're maybe lost your ability to speak or you lost your hands or anything else, your brain still functions and you can still send it the order, the instructions to move the hands and the idea is to use some machines to read those thoughts from your brain and perform the task for you. So, we have a bunch of studies that were done before by groups all over the world that show for instance that they are able to take paraplegics and recorded motor activities from part of the brain that is in charge of sending the instructions to move their hands and basically have cursors on the screen move based on those instructions.

Kerri Smith: And so what kind of angle do you come at this from, how did you want to extend that body of work in this new study?

Moran Cerf: Okay, so there are two things that we do that is different. One is these neurons that are not typically used for motor activities, so our neurons are memory neurons or neurons that are used by patients to encode and decode information. So you can kind of remember works done and published in Nature in 2005, the so-called Jennifer-Aniston neurons, those are neurons that were found by a colleague of mine that showed that when a patient thinks of Jennifer Aniston or actually thinks of anything related to her those neurons fire and we used those type of neurons to actually activate machines.

Kerri Smith: So these neurons that are responsible for abstract concepts if you like and aspects of memory so as you say Jennifer Aniston is only one neuron that might respond to a particular stimulus involving her.

Moran Cerf: Exactly.

Kerri Smith: And what you did is, you took electrodes and you put them into the brains of human patients, is that right?

Moran Cerf: Yeah, there are some types of people, particularly patients with epilepsy, that actually are candidates for this unique surgery and the ideas indeed that you're able to implant electrodes deep inside the brain and by putting the electrodes we can actually look at the seizure as it happpens and then we can figure out or the doctors can figure out what part exactly is the initiating part of the epilepsy and we kind of piggyback on that because when a patient sitting in bed for about 10 days with those the electrodes into their brain waiting to have seizures, and then we asked them would you mind also helping science by taking part in all kinds of studies with those electrodes in your brain.

Kerri Smith: And so the set up of this study what did you have them do?

Moran Cerf: Okay, so first in the morning we find neurons that respond to particular pictures and then we had the patient basically think of one of them, so we would tell him in trial one you trial task is the spider, you got a picture of the spider and a picture of the Eiffel Tower together on the screen and we wanted to focus your thoughts on the spider and by doing so you're going to enhance the visibility of the spider at the expense of the Eiffel Tower picture, so the more you think of the spider, the more it would be fading into the screen and the Eiffel Tower would fade out.

Kerri Smith: And people could do that, I mean that's pretty remarkable.

Moran Cerf: It's pretty remarkable and they're pretty excited. So we tell them, now, actually we are going to show something remarkable, you can move things on the screen with your thoughts and they sit there and they just thought thinking and just by doing so things move on the screen.

Kerri Smith: Now what does this tell you fundamentally about how the brain is choosing between options?

Moran Cerf: Okay, so the remarkable thing that we learned from this study was that our cases, where I tell the patient think of say in this example, there is a spider and there is Obama and I told the patient focus your thoughts on the spider and the patient is unable to do so. For some reason he is not able to focus his thoughts on the spider but he looks at the Obama picture, the more he does so, the more he sees the picture of Obama and he basically fails, but then just before he gets all the way to the end, he is able to kind of gather his thoughts if you want and focus in his mind on the spider and so what's happening in this patient is that although his brain sees through his vision system he sees Obama, his mind thinks spider, and just by that he is able to override the division with his imagery and make the picture of the spider reappear. So in a way there is a suggestion that is very unique, you see one thing, you think another thing and the thought in your mind wins and it kind of triumphs this vision. In the paper we titled it idealism triumphs realism.

Kerri Smith: Which I suppose is kind of a model of internal thought, you know.

Moran Cerf: Exactly.

Kerri Smith: I can think about my holiday in France this summer whilst being sitting here in the studio in London.

Moran Cerf: Exactly, yeah, that is pretty beautiful to think that in a way what's in our mind is always stronger than what's offered to us in the environment, it's almost like a Buddhist point of view.

Kerri Smith: So is it any clearer to you how internal thoughts or even will I suppose regulates how the external world is processed?

Moran Cerf: So certainly we could only put the electrodes only in the end, we only put the electrodes very far in the medial temporal lobe, we don't really see that what is coming to it, so we don't know exactly what the patient does to the systems before, we only see the end-result, we see it somehow one that is working and the other one is not and we can assume that somehow the patient changes the flow of information, the patient somehow talks to the machines behind those neurons and makes them change their flow or maybe send more kind of waves of information to this side and not that side but we don't really access to that part, we only see the bottom line.

Kerri Smith: Oh, I see. I've got a kind of philosophical question to throw at you. People in philosophy talk about the mind-brain problem and this idea that maybe the mind is synonymous with the brain or maybe they are two different things and you say in the paper these people are regulating the activity of these neurons, but what are they regulating it with?

Moran Cerf: So, that's a beautiful question, so the question is who controls who. Is the person controlling the neurons or the neuron controlling the person or are they the same?. In a way this work kinda makes us forget that this is a thing. We always think of the person and this is controlling the puppet called these neurons but in a way the same machine. So somehow those neurons get information, change their behavior and actually perform the task.

Geoff Marsh: Moran Cerf talking to Kerri. Look out for a video about Moran's research made by the man himself on our YouTube channel http://youtube.com/naturevideochannel.

Charlotte Stoddart: Now over to our friends at Scientific American for 60-second science.

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Cynthia Graber: This is Scientific American's 60-second science. I am Cynthia Graber. This will just take a minute. Take a deep breath, taste anything? Actually your lungs may because scientists have discovered that that the same receptors that exist on the tongue to taste bitter substances are also found on the smooth muscle of the lungs. Researchers were studying the receptors on smooth lung muscles that regulate contraction and relaxation of the airways. That's when they made the discovery which was so unexpected that the researchers themselves were skeptical. Finally they became convinced that the receptors were really there. They were not clustered in taste buds as they are in the tongue. The scientists then exposed human and mouse airways to various bitter compounds to gauge the effect. Many toxic compounds are bitter. So the researchers expected the lung muscle to tense up and contract to compel the breather to move away from whatever was bitter and perhaps toxic, but in a second surprise, bitter compounds relaxed and opened airways better than any existing asthma drug. The study is in the journal Nature Medicine. Researchers will continue to search for the role of the receptors; meanwhile the work represents a surprising new lead in the search for drugs to treat asthma, emphysema, or chronic bronchitis. Thanks for the minute. For Scientific American's 60-second science I am Cynthia Graber.

Charlotte Stoddart: Joining us in the studio for the news chat this week, is Nature news reporter Dan Cressey. Hello, Dan.

Dan Cressey: Hello.

Charlotte Stoddart: This week we've been hearing quite a lot about Haiti because of the cholera outbreak but you've brought us some slightly different news about Haiti. Nature 467, 1018-1019 (28 October 2010)

Dan Cressey: Yes, well cholera is a big concern there at the moment. A bunch of geoscientists have been looking at the recent quake in January and also seeing what that might mean for the future risk to the island and they found that a lot of the initial conclusions about the earthquake were in fact mistaken.

Charlotte Stoddart: So what did we think about the earthquake and what do we now know?

Dan Cressey: Well previously it was thought that the quake was due to one particular fault in the region which is already known and some of the papers which have been published in Nature Geoscience show that actually there may be a previously unknown subsidiary fault which is responsible for the earthquake. But more importantly for the people living in the region, some of the scientists who have been studying fault thing that not all of the strain that had accumulated as these two plates of rocks push past each other has actually been released and obviously there's still strain there that could be released in future as another earthquake.

Charlotte Stoddart: So two rather worrying bits of news that so one is that we thought we knew what caused the quake and actually it turns out we might be wrong and two, there could be another quake in the near future.

Dan Cressey: Yes and sadly all that can really be said at the moment is that when Haiti is being rebuilt that needs to be rebuilt as strong as possible.

Charlotte Stoddart: Okay, now the next story is perhaps not good news either and Dan it's all about how many people are dying from malaria? Nature 467, 1015 (2010)

Dan Cressey: Yes and whichever way you look at it it's not a good number. The World Health Organization currently says that it thinks around 30,000 people die of malaria in India each year. But a paper published last week in the Lancet puts a massively high number on this and that paper says that it could be anywhere between 125,000 to 277,000 which is obviously a pretty serious discrepancy.

Charlotte Stoddart: So why this huge difference in people's estimates of the number of malaria deaths?

Dan Cressey: Well this is all down to how you actually calculate deaths in a country that lacks some of the systems we have in the more developed world, for saying this what people died of. Now the paper that was published last week relies on asking doctors basically what they thought people died of and if someone says we think this patient died of malaria, that is listed as a malaria death. And a number of people have criticized this approach and say that a more statistical and proballistic method of doing things would yield a more accurate result and what you will be doing in that case is assign probabilities to each individuals death, so to say there is a 70% chance that this patient died of malaria and maybe a 30% chance they died of something else which has similar symptoms and what you can then do is aggregate all of those probabilities and apply that to the entire numbers of deaths that have been known to have occurred and hopefully get a slightly more reliable figure out.

Charlotte Stoddart: So this all stems from the fact that you know it's very hard to sometimes determine the cause of death and even though a doctor might say maybe this person died of malaria we can't be sure.

Dan Cressey: Yes exactly and there are also some potential biases in here and that if you are a doctor and you're working in a region that's known to have a high risk of malaria and you see something that looks like malaria you might be quite inclined to go that's malaria or it's actually if you're taking a broader view there is a chance that it wasn't and that it was something else.

Charlotte Stoddart: How are we going to sort this out then, because knowing, you know, roughly how many people are dying of malaria is pretty important I imagine?

Dan Cressey: It is, over time this statistical methods are probably going to be more reliable but equally there's a quite a big chance of the WHO's figure of 30,000 people dying of malaria in India is an underestimate, so the Lancet figure even thought it's much higher at a 125,000 it might be closer to the truth, even if the method it uses is perhaps not ideal in some people's eyes.

Charlotte Stoddart: Also in the news this week, a commercial space travel got a boost with the opening of the first space port runway and Dan, you've come with some news of what space tourism might do to the environment. Nature 467, 1006 (28 October 2010)

Dan Cressey: Yes, although it's really early days, there's a lot of excitement about maybe being able to fly into space for people who don't have to spare million dollars at the moment. But some people are starting to become concerned about what our huge number of rockets taking people into space might mean for the environment and especially for climate change and there's a new paper out and it suggests that if there were a thousand commercial space flights a year that could put as much black carbon into the atmosphere and do as much damage as current global aviation does in total.

Charlotte Stoddart: Now a thousand space flights a year. That sounds like an awful lot I mean, are we really expecting that many space flights?

Dan Cressey: Well that's a huge number of space flights a year, if you workout how many that actually is today, but it's worth remembering that commercial spaceflight is a necessarily just going to be tourists going up. There's a huge industry in putting satellites into space and some of the more ambitious predictions of space tourism are looking at around two flights a day. So this could, not in the near future, but in the long term future be a realistic number and there's also a complicating factor that some of the new commercial space flight people are looking at a slightly cheaper engine design, which is actually slightly worse to the environment because the sort of fuel that it burns.

Charlotte Stoddart: What are we going to do about this? Do these authors make any recommendations?

Dan Cressey: No, this is more to showing the impact that you can have with a concentrated release of some of these greenhouse gases at a particular point in the atmosphere. This hasn't spread everywhere, this is looking just at one launch site and yes, there is not a lot that you could probably do about that, although I guess you could say that people who are rich enough to afford commercial space flight can probably afford to offset their carbon emissions.

Charlotte Stoddart: Okay Dan, thanks very much all those newsy delights are yours for free at http://www.nature.com/news.

Geoff Marsh: And get involved next week for 3D holographics, imagine avatar but without the specs. I am Geoff Marsh.

Charlotte Stoddart: And I am Charlotte Stoddart. I wonder if there are Nature Podcast Neurons?

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