Nature Podcast

This is a transcript of the 24th March 2016 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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Kerri Smith: This week the brain cells that make some rats thrill seekers and others over-cautious.

Karl Deisseroth: We could instantaneously convert them from risk seeking to risk averse.

Adam Levy: And how to go from make-use-dispose, to make-use-repair-reuse.

Walter Stahel: Whatever I have, I try to figure out how long I can use it and that's why I've kept my first car from 1969 and I'm still driving it.

Kerri Smith: Plus using magnets and radio waves to control the activity of an animal's cell.

Jeffrey Friedman: In some of the studies we published earlier we could just change the activity of a gene by literally waving a magnet that was bought at a hardware store over the liver of an animal.

Adam Levy: This is the Nature Podcast for March the 24th 2016. I'm Adam Levy.

Kerri Smith: And I'm Kerri Smith.

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Adam Levy: Scientists have known for a long time that changing the electrical activity of brain cells affects their function. That's why electroshock therapy is still used to treat a range of psychiatric disorders. But over the years we've got better and better, controlling the electrical activity of specific regions of the brain. To treat diseases like Parkinson's, for example, an electrode can be implanted to stimulate neurons in a part of the brain. But the problem with methods like these is that they require a permanent implant in the brain which is very invasive. Wouldn't it be great if you could just turn cells on and off with just a radio wave or a magnet? Well, Jeffrey Friedman and collaborators at Rockefeller University in New York definitely thought so. I called Jeffrey out to find out about their new approach. Nature 531, 647–650 (31 March 2016)

Jeffrey Friedman: So we developed a method that allows you to control the activity of nerve cells and other cells now using a magnetic field. This system takes advantage of two different components: the first component is a channel known as TRPV1. TRPV1 is a receptor in your tongue and also nerve cells that senses thermal pain. So this is the channel that's turned on if you eat a hot piece of pizza and recoil. Now our original idea was this. Everyone knows that if you put metal in a microwave it heats and so our idea was that if we could put this ferritin iron-binding protein in proximity to the channel and expose it to a radio wave, the particle would heat and that would open the channel. And indeed we found that to be the case. But later on we tried using just a magnet rather than a radio wave and found that also was capable of opening the channel. We think this adds another arrow in the technical quiver that allows us to ask questions about how particular nerve populations control activity.

Adam Levy: So, you've got a way of tethering this ferritin to the channels of cells but how do you get it access to that place in the first place if we're looking at the brain?

Jeffrey Friedman: We deliver these proteins by introducing the DNA molecules or genes that would direct our expression and in order to do this, we need to inject a virus into specific parts of the brain. I think it's absolutely fair to say that it is invasive in terms of introducing the constructs but at the same time, you can, after the fact now, regulate the cells without the need for an implant.

Adam Levy: So now that you have these little controls in certain parts of the brain that you can control with a magnetic field, what do you actually do with them? How do you control them? Do you just wave a magnet about?

Jeffrey Friedman: Well yes, in some of the studies we published earlier as we were developing this method, we could just change the activity of cells or at least in this specific animal we did change the activity of a gene by literally waving a magnet that was bought at a hardware store over the liver of an animal. In the current experiments, we deliver the magnetic field simply by changing the proximity of an animal to a standard MRI machine. I think clearly in future, we'll want to develop devices that can deliver the appropriate strength magnetic field without the need for either hand waved magnet or an MRI machine.

Adam Levy: So, in this experiment, you're actually looking at a part of the brain called the hypothalamus. What function in the mice were you looking at?

Jeffrey Friedman: So, the hypothalamus is a very specialized and important part of the brain. It's at the base of the brain and it plays a critical role in controlling most, if not all, basic bodily functions. We've been interested for some time now in studying brain circuitry that controls metabolism and feeding behaviour and so we applied the method that enables magnetic control, radio wave control, neural activity, to ask the question, what is the impact of either activating or inhibiting neurons in this part of the brain on glucose metabolism and feeding? And what we found was is that activating, the glucose sensing cells of the hypothalamus increased blood glucose, it nearly doubled it and also increased feeding behaviour. It really illustrates to my satisfaction at least that the brain is really a very key site at which blood glucose is sensed so it's almost as if there's a very powerful controller in the brain that controls these two basic biologic functions.

Adam Levy: Was this something that was expected about the hypothalamus or is this genuinely news to you?

Jeffrey Friedman: Well, I think it was surprising me I'll leave for other people to decide whether it was surprising to them.

Adam Levy: Obviously this is the kind of thing that ideally we would like to somehow one day be able to use in humans. Apart from the complications of actually getting the virus into the brain in the first place, how would you even be able to get a magnet that was strong enough to get through a human skull?

Jeffrey Friedman: We're a long way away from a clinical therapy being derived from this. It's certainly something we'd like to explore but many steps have to be taken before we could even contemplate a human set of experiments, of course. Some of those steps will include making less bulky, portable, may be even wearable devices and until we begin to model what sort of field strengths we would need to control neural activity, how we will deliver fields of that strength and we're also thinking of their ways to improve the sensitivity of the system, obviously the more sensitive the system becomes to a magnetic field, the less power would be required in the device.

Adam Levy: That was Jeffrey Friedman. Check out his paper over at http://www.nature.com/nature.

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Kerri Smith: Coming up later in the show, turning thrill seeking rats into risk averse rodents but before that turning trash into treasure. Here's Charlotte Stoddart.

Charlotte Stoddart: Sky scrapers, cars, pieces of furniture: they start out as shiny objects of desire but pretty soon most end up in landfill, even sky scrapers. Last year, the United States threw away some 75% of its construction and demolition debris. What a waste. There's growing interest in alternatives to this make, use, dispose attitude. Proponents like to think of these alternatives as the circular economy. It's about more than just recycling. It's about repairing, updating, and reusing items and if that's not possible, breaking them down into their constituent parts and using them to build something new. Nature 531, 435–438 (24 March 2016)

Martin Charter: Basically, it is about using your resources much more efficiently and productively and really denying materials going to landfill.

Charlotte Stoddart: That's Martin Charter, Director for Centre for Sustainable Design at the University of Creative Arts in the UK.

Martin Charter: What we see in reality is that many companies still really don't think about what happens to their products at the end of life. So I particularly remember doing some training in Hong Kong with 20 individual Hong Kong based companies and only one of the 20 companies had any idea of what happens to its products at the end of life.

Charlotte Stoddart: Martin would like companies to take responsibility for the lifespan of their products and you can't just start thinking about this when you're about to knock a building down. You have to start at the design stage.

Martin Charter: So, it's designing in for example, dismantability, upgradability, repairability. There is a very big difference between, you know, cosmetic repairs to a piece of furniture that may be happening through charities through to whole new business models that are designed to enable multiples lives out of products.

Charlotte Stoddart: And a few companies are doing it, construction company BAM is starting to design elements of their building for disassembly promising to buy back some structural materials and return them to suppliers and the photocopier maker Xerox…

Martin Charter: Claim they get seven to eight lives out of their photocopier platforms by designing in dismantability and upgradability. So essentially really it's a strong element of product-life extension.

Charlotte Stoddart: That approach wastes less materials but also means Xerox can make more money by reselling their reconditioned products. It might seem like this vogue for reusing and recycling is a new trend, but it goes back to the 1970s when a young Swiss architect called Walter Stahel wrote to the European Commission with an idea.

Walter Stahel: I'm Walter Stahel and for the last 40 years, I've pursued the same idea and I'm still doing it.

Charlotte Stoddart: Walter wrote to the commission to highlight how wasteful it is to dispose of old products instead of repairing them.

Walter Stahel: As an architect I knew that in refurbishing an existing building, it takes much more labour, but of course you save about 80% of the initial resource than its input and I thought the same could also apply to manufactured goods such as cars. So, therefore the fact that in the 1970s we had high unemployment and the energy prices jumped three-fold gave me the idea that logically we should use more labour and less energy, less oil because that is common sense.

Charlotte Stoddart: Today energy prices might be relatively low but there's a strong environmental argument for saving resources and even with low energy prices, Walter says the approach can save companies money.

Walter Stahel: Remanufacturing goods for example is about a third cheaper than manufacturing an equivalent new one and so you'd expect that some people jump on the opportunity to remanufacture goods but that does not happen.

Charlotte Stoddart: Why doesn't it happen? Partly because it involves changing whole business models and that's difficult. Martin Charter again.

Martin Charter: If a company has a successful business model, they don't necessarily want to change that and any change from one model to another takes time and effort and retraining, reconfiguring systems etcetera .

Charlotte Stoddart: But there's another problem says Walter. We simply don't know how to disassemble and reuse many materials.

Walter Stahel: The effort of most universities especially the hard sciences goes into developing better new materials but I don't know any university at the moment that is doing research or training of chemists or engineers on what I call the area of delaminating, dealloying on splitting molecules because it's only if we can split molecules and recycle pure atoms that we can really close the loop and really use materials forever because the focus is still on manufacturing.

Charlotte Stoddart: Perhaps companies and individuals should follow Walter Stahel's example.

Walter Stahel: I basically use life as an experiment, whatever I buy or whatever I have, I try to figure out how long I can use it and that's why I've kept my first car from 1969 and I'm still driving it. The willingness of the owner to make sure the thing does not become waste that makes a long last product.

Kerri Smith: Walter Stahel and before him Martin Charter talking to Charlotte Stoddart. To find out more about the researches and companies trying to close the loop and redefine waste as a resource, check out a special collection of articles in this week's Nature at http://www.nature.com/thecirculareconomy and if you've recently found new uses for old materials yourself or if you're one of those rare scientists studying recycling rather than making, why not let us know your current project. We're on email, mailto:podcast@nature.com and on Twitter mailto:@naturepodcast. Coming up in the news chat, China's five year plan for science and how scientists are using Apple's research kit. That's after the research highlights with Corie Lok.

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Corie Lok: At the Paralympic Games, runners who wear a left leg prosthesis could be at a disadvantage compared to those with a right side one. That's because races are run in the counter clockwise directions. Athletes with the left leg prostheses would always have the prosthetic leg on the inside of the curve track and that slows them down more, then people who have their prosthetic leg on the outside of the curve. Researchers noticed this when they studied videos of running amputees and measured the speeds of the athletes. The researchers say that the inside foot spends more time in contact with the ground than the outside one when running on curves and this lowers running speeds. The study was in the Journal of Experimental Biology. Nature 531, 417 (24 March 2016)Cancer cells grow fast and have huge appetites. They suck up nutrients from the blood stream and it turns out they also receive little care packages of nutrients from surrounding healthy cells. Researchers study these tiny membrane bound sacks called exosomes. They looked at exosomes generated by cells from healthy human tissue that was near prostate and pancreatic tumours. They found that when cancer cells took up these exosomes, the tumour cells increased their metabolism. Inside the exosomes were amino acids and other nutrients that helped to sustain tumour growth when other nutrients were in short supply. The study was in the Journal eLife. Nature 531, 417 (24 March 2016)

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Kerri Smith: So, Adam in the lead up to this next bit I have a choice for you. In front of you are two groups of paper cups, these ones on your left they hold a guaranteed one chocolate button. So every time you pick this side, a cup from this side, you know you'll get a chocolate reward.

Adam Levy: I do like chocolate.

Kerri Smith: Are you a bit hungry?

Adam Levy: Yeah, I could definitely use all those cups.

Kerri Smith: Now those ones on your right, there's a 25% chance that you'll get multiple buttons, four buttons at once but that's only the case in one of these cups and if you pick any of the others that's a 75% chance you might get only one quarter of a button which is just not even worth having.

Adam Levy: I don't want one quarter of a button, I want four buttons.

Kerri Smith: But how much do you want it? Are you going to pick from the left where you got a guaranteed reward that's very small or you going to gamble on the right?

Adam Levy: I feel like I'm meant to be picking the one on the left.

Kerri Smith: There's no right or wrong.

Adam Levy: You say that, but you're looking at me in a very judgmental way. So, I feel like I'm meant to pick the one on the left like a good sensible person.

Kerri Smith: Have a go.

Adam Levy: Well, I don't want to pick the one on the left, I want to pick the one on the right. Okay.

Kerri Smith: There you go and have you done?

Adam Levy: Oh I've got quarter of a button.

Kerri Smith: Oh, chocolate dust.

Adam Levy: Disappointing.

Kerri Smith: It's, you got a bit unlucky there but if you do this, it turns out in enough people over enough time, you see that there are individual differences in how much risk people are willing to take and people are very consistent over time. So perhaps you're just a thrill seeker or risk taker by nature. Some people are just riskier or more cautious. Now the chocolate button test that's an exact parallel of a recent study in rats. Only the rats got little micro litre drops of sugary water rather than chocolate. Do you want to know the button?

Adam Levy: Yes.

Kerri Smith: Now what the researchers were trying to get at was firstly do rats have the same personality differences in riskiness as people and secondly which circuits of cells in their brains are coordinating these traits and finally can their risk profile be altered? Can risk loving rats or risk loving Adams be made to take the safer bet? Here's the lead author on the new study. He's a veteran of the show for those who've listened for a while: neuroscientist and psychiatrist, Karl Deisseroth at Stanford University. Nature 531, 642–646 (31 March 2016)

Karl Deisseroth: If you think about the course of human history, I think it's clear that willingness to take risky ventures has been crucial to our success and our survival. On the other hand, as we all know, it can come with very serious adverse consequences as well and it shows up both in the course of normal life and in psychiatric disease and so it's a very interesting question how the possibility of unfavourable outcomes, the recent history of unfavourable outcomes, how those are played out in the brain and how they affect behaviour.

Kerri Smith: So, there's a general human interest, there's a clinical interest and what was left to know about risk because we do have some understanding of which bits of the brain are processing it.

Karl Deisseroth: Yes and so we were interested in going beyond the sort of a region of the brain type understanding and we wanted to address what you might call the circuit dynamics of risk. During the actual moment of consideration of the possibility of an unfavourable outcome and choosing to take a more risky compared to a safe course, which activity patterns and which cells were not only active but possibly important.

Kerri Smith: So, these are the cells that are, sort of, should I stay home, should I go out, should I bungee jump, should I stay on this platform?

Karl Deisseroth: More or less, yes.

Kerri Smith: So, here then you set up a study where you first figured out whether rats were thrill seekers or safety lovers and then you used optogenetics which is this technique that you developed which can turn neurons on and off using light and use that to interfere with the signals that neurons are sending to each other, all taking place in this region called the nucleus accumbens.

Karl Deisseroth: Yes that's right. So, with optogenetics we can provide or inhibit activity signals in targeted cells and with great temporal precision, and so in a task like this we have the capability of delivering the optical stimulation to the targeted cells at exactly the moment that we want during the task i.e. during the decision period or during the reward consumption period for example.

Kerri Smith: And it's quite dramatic what happened. So here's the rat; t's choosing between the safe lever and the risky lever and just as it is doing that, it gets this little bolt of light in this certain group of cells and then what?

Karl Deisseroth: Well, the striking thing was that we could instantaneously convert them from risk seeking to risk averse even at a single trial level, but we could also do it in a more stable pattern over the course of day or more and so what this showed us was that this precisely timed pulse of activity was able to change the trait behaviour of the animals.

Kerri Smith: What information is it therefore standing in for, like what is that signal doing that changes their decisions?

Karl Deisseroth: Ah! well here's where the other side of the study comes in as we were also very interested in observing what is normally happening in these very same cells during exactly these task at these exact times. We found that animals that had just come off an unfavourable outcome, so they had chosen risky and lost. They got that tiny negligible little bit, they had a very striking pulse of activity during their next decision, when they next had to come and decide which lever to press. It looked as if it was a signal saying effectively hold on, probably not the time to take the risky choice.

Kerri Smith: The cells you found and the signal you found them sending are all that you were able to then artificially put in was basically the kind of 'are you sure you want to do this?' cells?

Karl Deisseroth: Right, I mean, I think that's exactly how we think about it in the lab of course at what level the animal is aware of the nature of the decision being made is a very interesting question we can't answer.

Kerri Smith: We feel like in some fields, let's take politics it would be helpful for people to look more at their previous or their predecessors previous experiences to have these flash a little more heavily at them?

Karl Deisseroth: Well yeah, you're right we need a social version of this where other people's recent unfavourable experiences are relevant.

Kerri Smith: Bit of a stretch, so basically people and rats are risk takers because perhaps these unfavourable previous outcomes don't affect them so much, they're more kind of optimistic about it.

Karl Deisseroth: Well yeah, this is a great question. So, then we looked at the rats with different trait variability and we looked at those naturally occurring signals and we found indeed that the risk seeking animals did not muster at the decision time nearly as much of this hold on signal.

Kerri Smith: And with your psychiatrist back on just at the end here Karl, some drugs have these unintended side effects of making people take more risks and also some psychiatric disorders themselves have as part of their symptom profile increased risk taking. I mean, what did these findings, basic science as they are, what kind of insight did they give you clinically?

Karl Deisseroth: Well, I think, there's a primary and overwhelming clinical relevance which is simply understanding and that may sound simple but for psychiatry just to be able to tell people, to tell patients and families and society more broadly that there is a real biological basis for these traits and these states that people can get into. That brings, actually by itself, hope and understanding.

Kerri Smith: That was Stanford's Karl Deisseroth picking apart risk seeking behaviour in the brain. There's a News and Views about the research in the journal this week and if you're interested in the latest developments to the technique optogenetics, there's another report in Nature Methods. That just came out last month, which has more detail about how the team has been making it more precise, in space, in time and in strength, http://www.nature.com/nmeth.

Adam Levy: Time now for this week's news chat and Richard van Noorden joins us in the studio. Hi Richard.

Richard van Noorden: Hi Adam.

Adam Levy: Now, last week on the show, we were discussing China's emissions and since we recorded that, China's 5-year plan has been approved. What's the big news for China's greenhouse gas emissions? Nature 531, 524–525 (24 March 2016); Nature 531, 425 (24 March 2016)

Richard van Noorden: Well, the big news from China's five-year plan is that greenhouse gas emissions could peak much sooner than forecast. We're seeing a very rapid reshaping of the energy sector in China. At the UN Climate Summit in Paris last year, China committed to halting its growth in emissions by 2030 but many people think that a peak could come by 2025 if not sooner and there's also a shift away from heavy manufacturing, the production of steel and even the use of coal.

Adam Levy: Last week, when I spoke to people about China's emissions, everyone said to me that China's real concern is air pollution emissions, now is there anything in five-year plan which specifies how they're going to try to limit air pollution going forward?

Richard van Noorden: Well, there are strict new requirements on curbing air pollution essentially driven by angry citizens. There's a commitment to cap energy consumption, which should see a reduction of coal use, but the five-year plan doesn't really specify how China is going to achieve its targets. The government's already trying to cut the levels of air borne particulate matter. Just next year, it wants to cut the Beijing air pollution by a quarter from 2012 for instance and there's major initiatives outlying to tackle environmental protection, clean energy, smoke in Beijing, fertilizer pollution in Lake Tai in Shanghai. Funding for all of this to control air pollution alone is going to increase by at least four times, we were told, and there are labs focusing solely on clean energy, environmental research and water pollution control technologies. Well what does all this mean? I mean practically speaking it doesn't mean that these measures will have an immediate effect but it does mean that the whole country is essentially going to become a whole laboratory for environmental research. So it could be the more exciting research areas to come out of the five year plan will be pollution control.

Adam Levy: But of course the five-year plan isn't all an environmental plan?

Richard van Noorden: So, we had a look at China's brain science and listeners might remember that the US, Europe and Japan have all announced massive projects to map the brain and China's brain science plan is due to be officially announced shortly. It's expected to focus on brain disease and on artificial intelligence. China's scientists know that they are behind the rest of the world in terms of top level talent but they have a few factors that could help them catch up. The Chinese Neuroscience Society now has 6000 members compared to just 1500 a decade ago and the country sadly has tens of millions of patients with psychiatric or degenerative brain disease that will make clinical studies easier and it has hundreds of thousands of research monkeys which has already allowed Chinese researchers to take the lead in using gene editing to produce models of autism in monkeys.

Adam Levy: China also seems to be taking stem cell research more and more seriously.

Richard van Noorden: Yeah, well there's going to be a massive new funding initiative called stem cell and translational research and the grant for this going to be awarded on a new kind of competitive process. Previously, critics said that you tend to get grants if you have political connections rather than merit, perhaps a familiar complaint about research in China and other countries. Following the last five-year plan China invested about 3 Billion Yuan which is just a half billion dollars in stem cell research and we were told that there'll be a big increase over the next five years; we didn't get figures but China clearly sees the promise of stem cell and regenerative medicine as one of the key thrusts for modernizing its medical services system.

Adam Levy: Moving onto our second and also quite a medical story, researchers have been using apps to collect data on patients. Nature 531, 422–423 (24 March 2016)

Richard van Noorden: Last year Apple debuted its research kit developed in house, it's like an app that you open on your iPhone and scientists were allowed essentially to create research projects in this app where hopefully people will put in information, so we've kind of checked in on how these smartphone research kit programs going and researchers are being quite impressed with what they can do. Now there are about 25 apps in research kit, tracking anything from autism to breast cancer, Parkinson's disease and the researchers who use these apps say what they get is scale. There's an app called mPower that tracks people with Parkinson's. It's enrolled more than 6800 users which is three times the number of subjects in the largest previous Parkinson's study.

Adam Levy: When you're collecting data like this, do you know whether you're getting accurate data in the same way you would if you actually brought someone into a lab?

Richard van Noorden: Right, so in these apps the people who are doing the study don't meet the people who are putting in their data so obviously that's a question. Now researchers are basically trying to spot check their app data. So one team working on an asthma app, they examined whether the height and gender of their users correlate with the peak flow of breathing and if that does, which it does, it suggests that you're not randomly getting bad data from your participants, so there's essentially ways to crosscheck whether your data is of high quality. Now, there is a question about whether apps can keep users engaged over the long term. For example the Parkinson's app I was talking about uses the accelerometer and the microphone to measure the steadiness of the gait of the users and their speech but only about a thousand of these 6800 users have elected to fill out a survey that assesses their cognitive functions. So, there's a real drop off in interest as what you're asked to do gets more difficult and time consuming.

Adam Levy: Why would users want to do this in the first place, I can see why it's very advantageous to researchers but is there any direct benefit participants?

Richard van Noorden: Well the problem is I don't think that people developing these apps know their users particularly well. A lot of people seem to be very happy to share their data by putting in these apps but beyond that it's very remote and you're not meeting the participants.

Adam Levy: What researchers are actually hoping to do with all these new found data?

Richard van Noorden: Well, it's perfect for example for clinical trials of drugs. So, Roche, the pharmaceutical firm in Switzerland has developed its own Parkinson's app and it's using it in a clinical study because you can collect data from participants daily rather than say once every three months, you can really see how they're progressing on their new pill. Now other people suggest that eventually you might get wearable devices that could automatically collect information about users in real time and perhaps collect insights into how to detect and prevent disease. And on 21st of March, Apple said that these apps can now import genetic data from 23andMe if of course the user wants that to happen. So you could potentially have a rich connection between the genetic data and what you're collecting in the app about your user.

Adam Levy: Thanks Richard, check out those stories at http://www.nature.com/news and for more on China's emissions check out last week's podcast. That's all for this week. Next week, why people are so mean to each other online and how one scientist has been stopping the spats.

Kerri Smith: Got a feedback. Drop us an email on mailto:podcast@nature.com, tweet at @naturepodcast or just give us a few stars on iTunes. I'm Kerri Smith

Adam Levy: And thanks to popular vote, I'm Boaty Mc-boat-face.

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