Nature Podcast

This is a transcript of the 6th April 2017 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: slowing sown the race to fish.

Martin Smith: Fishermen's lives are actually at stake. Under these racing conditions they may take more safety risks at sea.

Adam Levy: And, a newly described cell receptor leaves scientists stumped.

Bryden Le Bailly: Frankly, it's confusing to someone who knows what they're talking about as well, I think

Kerri Smith: Plus, our pick of the spring's best books. This is the Nature Podcast for April the 6th 2017. I'm Kerri Smith

Adam Levy: And I'm Adam Levy.

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Adam Levy: About 80% of the world's fish stocks are being fished to the limits of sustainability or beyond. Authorities need to carefully manage fisheries to stop more and more of them from becoming depleted. Perhaps the most obvious approach is to take fewer fish out of the ocean by setting a limit for each fishery. But some fisheries have gone further, setting a limit for each individual boat or fisher. That last option is controversial. So, a paper out in this week's Nature, watches a real world experiment unfold to see whether it works. I called up author Martin Smith to see why authorities setting a limit on the total catch, and to each fishery, doesn't necessarily stop all the fishers rushing to catch as much as they can.

Martin Smith: Often, the first thing they do is to set an industry wide quota and that may actually put a stop to or reduce over fishing, but it can actually make that crazy race to fish even worse, so people even fishing as fast as they can to catch that quota before the season gets shut down. And there can also be other effects; so, fishermen might catch more of the none-target species, or what we would call by-catch. And also we have some evidence that suggests in this race fishermen's lives are actually at stake. People are engaged in a very dangerous profession already, and under these racing conditions they may take more safety risks at sea.

Adam Levy: So in this study you were taking a look at an approach in addition to these limits that might help fix the problem. Could you explain what that idea is?

Martin Smith: Yes, so the idea in the modern parlance is called catch shares. Essentially you take that industry wide cap and under catch shares you divide that catch up and you allocate it to individual fishing vessels or in some cases, groups of fishermen.

Adam Levy: What did we already know about how catch shares work in practice?

Martin Smith: Well we have quite a bit of evidence suggesting that cat shares really reduce the costs of fishing and there's some evidence suggesting that they're also good for the biological stocks themselves. But there's also some theoretical reasoning that suggests that when you put catch shares into place, you might slow the race to fish in such a way that fishermen can then take advantage of new markets. They might be able to sell more fresh fish instead of frozen fish. They may be able to time the markets and avoid gluts. So we really set out to test that conventional wisdom: do catch shares really slow the race to fish?

Adam Levy: So how do you actually end up showing this? It's not like a lab experiment where you can easily do controls.

Martin Smith: No, that's exactly right. It's not a lab experiment. It's what we would call a natural experiment. We have 39 different fisheries in the United States that have put catch shares into place. So what we do is we treat it as if it were a lab experiment. We take each of those 39 fisheries and we match each one to a very similar fishery in some other region that didn't receive the policy treatment at the same time so it ends up seeming very much like a lab experiment except that it's a natural experiment unfolding out there in the world.

Adam Levy: And when you do this natural experiment – I guess do is probably the wrong word – but when you observe this natural experiment, what do you see?

Martin Smith: We see that on average, catch shares really do slow the race to fish. So, we see that most of the individual cases show that there's this slowing of the race.

Adam Levy: How big is this effect actually? Are we talking, the season is a day longer out of 3 months, or…?

Martin Smith: Yeah, so for a one year fishery, on average, it takes about an additional month to reach that 70 or 80% of the catches. So that's a pretty substantial change and that's the average effect.

Adam Levy: Do you think this understanding helps fisheries plan for the future? Do you think more fisheries are likely to adopt catch shares as a result of this?

Martin Smith: All fisheries are different and every fishery really needs a type of regulation that works specifically for it but we feel that his evidence really solidifies some of the conventional wisdom of fisheries economics that's really been out there for a long time. It's a particularly important time right now in US fisheries' management because the main federal legislation that governs fisheries' management in the United States is up for reauthorisation in congress.

Adam Levy: That was Martin Smith. But does this study convince others that catch shares are a good idea? Andrew Rosenberg is at the Union of Concerned Scientists and has worked on fisheries for decades. He explains some of the problems with introducing catch shares in the first place. There's the problem that the system can end up favouring the biggest fishing businesses and then, of course, there's the soap opera of dividing up the assets.

Andrew Rosenberg: In any fishery where you're going to allocate opportunity to fish like this, there always is a difficulty in the initial allocation. Everyone has history in the fishery and trying to figure out then – do you get 2% or do you get 2.5% based on your historical participation? It's quite a difficult thing to do and always creates some kind of controversy or hard feelings. So, in practice it's still difficult but it is an effective mechanism for changing incentives. So it's not like one study will be the watershed study but we are accumulating more and more evidence and that's a good thing.

Adam Levy: That was Andrew Rosenberg. Before him you heard from Martin Smith who's based at Duke University in the US. Find his paper and a News & Views by Andrew at http://nature.com/nature.

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Adam Levy: In the Research Highlights: brain implants and the menstrual cycle on a chip. And in the news, ancient human remains from Mexico. But before we get to all of that: the receptor that's stumping scientists.

Kerri Smith: Think of each of your cells as a fortified city. There are walls all the way around guarded by gatekeepers. When the right message arrives from outside of the cell – a hormone, say – the gatekeeper wakes up and passes a message into the cell. If drug molecules are to work on cells, they need to talk to the gatekeepers. The largest group of cellular gatekeepers are the G-protein-coupled receptors or GPCRs. Each one has a special messenger to relay their messages into the cell and send them on to G Proteins on the inside, hence the name. So drug companies tried to make replicas of the messengers to activate or block the gatekeepers. That's much easier to do if you know what the gatekeeper itself looks like and for many of them we do, but some important ones, not so much. There's this one receptor that responds to a hormone called angiotensin. The gatekeeper is called AT2R. 'AT' for angiotensin; '2R' for type two receptor, and this week a team reports some rare snapshots of it in action. And it is not gatekeeping in the way they expected. Nobody really knows yet what that means for how it works, but reporter Geoff Marsh spoke to Nature's biology editor, Bryden Le Bailly, for some hints.

Geoff Marsh: What do GPCRs do in the body?

Bryden Le Bailly: They sit in the membranes of your cells and they allow all of your cells to respond to the outside world. The membrane is there to protect them and the GPCR is there so that they can communicate.

Geoff Marsh: And they react to things circulating around the blood like hormones and…?

Bryden Le Bailly: Exactly, yeah. So, hormones, neurotransmitters – lots of different small molecules. So normally what happens is your messenger will come in and it will activate the receptor. That signal will then be propagated through the receptor by changing its shape and that will allow it to interact with the G Protein which is a signalling partner. So that means that the G Protein then goes off and does lots of other things and effectively that's your biology happening, right.

Geoff Marsh: And it's for that reason that they're also hugely important therapeutic targets.

Bryden Le Bailly: Yes, so there was a statistic a couple of years ago that said that about 40% of all modern drugs are targets for GPCRs, so you can't really understate their importance as such.

Geoff Marsh: In the paper that we're here to talk about today, they're looking at angiotensin receptors. Tell us a bit about those.

Bryden Le Bailly: Angiotensin is basically a hormone and that's involved in how your blood pressure is regulated. It's in lots of the major organs in your body and that basically leads to things like elevating and lowering your blood pressure and opening and closing your veins and arteries.

Geoff Marsh: And there are two types of these angiotensin receptors?

Bryden Le Bailly: Yes, so there's AT1R and there's AT2R – so those are just the two different receptors that both respond to these hormones.

Geoff Marsh: What do we know about their pharmacology?

Bryden Le Bailly: So there are already drugs that are being developed for, for example, treating hypertension. So, AT1R, when it' activated, raises you blood pressure so the drug that blocks that receptor will obviously lower that again, so that's an obvious thing that lots of people will be familiar with.

Geoff Marsh: So people developing drugs, do you think they'll have good reason to be interested in the type-2-angiotensin-receptor?

Bryden Le Bailly: So, we know less about it than we know about the type 1 receptor. We know that its implications are that it counterbalances how the type 1 works so for example it will lower blood pressure rather than elevating it. But there are other series of effects that we're not quite sure about at the moment, so that is why these people have set out to understand the structure.

Geoff Marsh: And one weird thing about this type 2 G-Protein-coupled-receptor is we think it doesn't actually interact with G-Proteins.

Bryden Le Bailly: Exactly yeah, so there haven't been any studies that have categorically shown that it interacts with a G-Protein in a normal way that all other GPCRs are known to function.

Geoff Marsh: So something fishy was clearly going on.

Bryden Le Bailly: Exactly, yeah.

Geoff Marsh: Tell me what they did in this study then.

Bryden Le Bailly: So what they did was they took a series of messengers that are known to block the type 1 receptor and they crystallised those with the type 2 receptor. Those allow this structure to be solved and so what this tells us is that these molecules that we know to block the type 1 receptor, they actually cause the type 2 receptor to form an active-like state. So it almost has the opposite effect on the type 2 receptor from how it does on the type 1. But, this active-like state is not like any state we've seen in a GPCR before because it causes the GPCR, the receptor, to block its interaction where it would happen with the G-Protein.

Geoff Marsh: So looking at this receptor from the outside of the cell – it paradoxically looks like it's in its active state as you might imagine it with the hormone angiotensin?

Bryden Le Bailly: Exactly, yeah.

Geoff Marsh: But on the inside it's actually got some weird little curly protein that's stopping it working.

Bryden Le Bailly: Exactly yeah, so the bottom of the receptor is essentially curled round to stop any interaction happening and any signalling happening.

Geoff Marsh: From a layman's point of view it almost sounds like this is a broken GPCR.

Bryden Le Bailly: Yeah and frankly it's confusing to someone who knows what they're talking about as well, I think. So this is why it's interesting – because it's completely unexpected.

Geoff Marsh: Do you think this is going to start to maybe explain some weird drug effects and why certain drugs don't work and all these sort of things?

Bryden Le Bailly: Obviously it's a speculation but it may well do. The thing you've got to remember is if this is a mechanism that we've only just uncovered, are there other mechanisms out there? How are these GPCRs activated or blocked, and what are they? And how are they going to impact our understanding of how these receptors work and how we can interact with them for pharmaceutical, therapeutic purposes.

Geoff Marsh: What are the limitations with this sort of study?

Bryden Le Bailly: The structure obviously is just giving you – it's frozen, it's like a sculpture. It's frozen in time, in stasis, and this receptor will access lots of other shapes and interact in lots of other different ways possibly and so this is just giving us one piece of that puzzle. One of the next steps will be to understand the dynamics of the receptor, how it interacts, and what time scales it interacts with, and that's all going to tell us a lot more information about the various different states that it can adopt.

Kerri Smith: That was Bryden Le Bailly who is as stumped by the structure as the scientists who've described it. Find more info in the paper and the News & Views article, both at http://nature.com/nature.

Adam Levy: We've had a revolving cast of characters in and out of the studio this week and next in the hot seat was Nature's Books & Arts editor, Barb Kiser, who dropped in to chat with Kerri.

Kerri Smith: Exactly right. Twice a year, in spring and autumn, Nature curates an essential reading list for the discerning scientist. There are six tomes making up the spring books package and Barb is here to talk about a couple of them. Hi Barb.

Barb Kiser: Hello.

Kerri Smith: Now, one book involves Bill Gates and Mark Zuckerberg and the other concerns a physician called James Parkinson. Tell us what connects these two.

Barb Kiser: Okay, so they're both about different sorts of legacy: one discovery and one dollars. The first harks back to the Enlightenment. There was an unusual polymath at the time who managed to diagnose Parkinson's disease so accurately that his description still holds. He wrote about it in an essay which this year is celebrating its 200th and that is the Essay on the Shaking Palsy. But the thing is, who was Parkinson? There's a new book called The Enlightened Mr Parkinson by an historian of Geology called Cherry Lewis. This book gives us the whole man.

Kerri Smith: This is a book about somebody that we naively might consider was at least a medic, if not, a psychiatrist. What is an historian of geology doing writing about this man?

Barb Kiser: Yeah, so he collected fossils at a time when geology was nascent and he co-founded the Geological Society with the likes of Humphrey Davy. The reviewer who's the medical historian Tilli Tansey relates that Parkinson was, first off, a London apothecary surgeon who performed, for instance, bloodletting and that sort of fairly mechanical medical intervention. He wrote on humane treatments and legal protection for the mentally ill in a book called The Madhouse and that was relatively rare also. So, in short, he was an amazing package: a medic, a radical, a palaeontologist, and of course living in a time when Priestley, and Davy and the great geologist William Smith were all living. So it's a really fascinating book and a wonderful review.

Kerri Smith: And what was Parkinson's London like? Because of course, he wasn't just concerned with the inhabitants of it who had, as he called it, 'the shaking palsy'. That was only one of his many interests. He was particularly concerned with his environment, wasn't he?

Barb Kiser: The Industrial Revolution was in spate. The air in London was already becoming quite bad and also the water wasn't great. There was also a lot of poverty and I think this is part of Parkinson's legacy, essentially, that some of his clients or patients were poor or lower middle class and he was finding solutions for people of that class so in addition to his work for the mentally ill and obviously for those with the shaking palsy, he was, I believe, a highly socially conscious person.

Kerri Smith: So it's kind of ironic isn't it that he's become known for this eponymous disease whereas, in fact he just had a finger in all the pies.

Barb Kiser: Absolutely.

Kerri Smith: His life and his work and how we remember him contrast quite sharply with the second population of people that we're going to talk about who are the subject of a book about Philanthropy.

Barb Kiser: Yeah, so whereas Parkinson might be characterised as endowing the world with discoveries, endowments of a different kind figure in the other book I'm going to talk about which is The Givers. And this is David Callahan's exposé of philanthropy and Philanthro-capitalism and their impact today. Callahan is a cofounder of the Think-tank, Demos, and he looks closely at the issue of how big money is dispersed and of course there is a lot of big money these days. Our reviewer, Anne-Emanuelle Birn, notes that the wealth of just 8 billionaires now matches the collective wealth of 3.6 billion people – that's the world's poorest. So, these individuals – and there are lots of well-known names there, obviously like Bill Gates and Mark Zuckerberg – in a way wield the power of governments but these individuals are very concerned about being nippier than, say, a government department or a big agency such as WHO. The UN these days is viewed as a lumbering giant in some circles.

Kerri Smith: Whereas these guys are taking on – and they are all guys – they're taking on glamour topics, or issues, or…

Barb Kiser: Yes, exactly, that is one of the issues that Callahan looks at. If you're looking at any one area, for instance, that area will have many issues, challenges, but it could be that an endowment is directed at, say, medical innovation. There is also criticism sometimes that the endowments are directed at diseases, certain cancers which may cluster among richer people. This is not at all to make a blanket statement about philanthropy or even Philanthro-capitalism. Bill Gates has done amazing things, obviously, in malaria and other areas. But, Callahan talks a lot about creeping plutocracy; these foundations and other bodies run by Philanthro-capitalists and their families are often less regulated, for instance than UN agencies or government departments. I think in an era when many politicians too are from the mega-elite, it's a question we simply must keep probing and looking at.

Kerri Smith: What should they do instead? Does the author or reviewer suggest how they should dispense with billions of dollars for the public good if not just to give it directly to projects?

Barb Kiser: So, Birn notes that former US Labour Secretary Robert Reich has said– or reminded us actually – that those governments once collected billions from tycoons – I'm quoting from the piece – then democratically redistributed these revenues. When you think about it, obviously, this is the sort of thing that Franklin Delano Roosevelt was doing. It was considered a norm in government before.

Kerri Smith: Alright, thank you Barb for teaching me a new word – Philanthro-capitalism – and for introducing those two books. They're part of a selection of science reads on issues such as refugee economics, a global history of energy, fundamental physics, and atmospheric interventions. Find all the reviews at http://nature.com/booksandarts.

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Adam Levy: No time for hundreds of pages? How about a couple of minutes for the highlights? It's science for the time-poor with Corie Lok.[Jingle]

Corie Lok: Researchers have recreated the human menstrual cycle in a dish. They grew mouse ovarian tissue inside chambers on the chip. Tiny pumps moved fluid through the chambers, mimicking blood circulation. Changing the levels of two key hormones in the fluid, according to the human menstrual cycle, caused the tissue to form and release eggs. It also made oestrogen and progesterone in line with the 28 day cycle. A different version of the chip contained not just tissue from the mouse ovary but also from the human fallopian tube, uterus, cervix and liver. All connected by pumps. This five organ system could be used to study the reproductive tract and test the effect of drugs. You can learn more from the journal Nature Communications.

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A man paralysed from the shoulders down can use his own hand and arm to feed himself. Thanks to a brain implant that is connected to key muscles in his arm. Previous neural prostheses have already allowed paralysed people to move a robotic arm. To get the 53 year old man to move his own arm, researchers placed 36 electrodes into arm muscles that control his hand, wrist, elbow and shoulder. They connected these electrodes to a brain implant. An algorithm translated brain signals into arm and hand movements. During trial sessions in the lab, the man could hold a fork in his hand, scoop mashed potatoes from a plate and feed himself several bites. He could also reach out, grab a cup and drink from it using a straw. Find out more from the journal, The Lancet.

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Adam Levy: Our final studio guest for this show is reporter Ewen Callaway who brings tidings of great news. Hi Ewen.

Ewen Callaway: Hi there.

Adam Levy: So, first a story of an ancient human. Of course, an ancient human – Ewen Callaway's in the studio. First a story of an ancient human. Now, who was this and why was she important?

Ewen Callaway: This particular ancient human, her nickname is Naia. She lived about 12,000 years ago in the Yucatán Peninsula in Mexico. Scientists discovered her remains a few years ago. What's cool is that they were in a submerged cave. A nearly complete skeleton: one of the oldest, most complete skeletons from the Americas.

Adam Levy: So are there other skeletons from the Americas from around that time or nothing really as complete as this?

Ewen Callaway: There are other skeletons – bits and bobs here and there but I think this is one of the more complete skeletons older than 12,000 years. That's what I would say.

Adam Levy: And now the news is that researchers are trying to unpick how she lived her life to some degree.

Ewen Callaway: Exactly, yeah, so initially when Naia's remains were found, they left her there, in this under water cave in the Yucatán but then there were some people who got in there – none archaeologists – and started messing about with it and so the archaeologists decided to take as much of Naia out as they possibly could including her skull and some of the bones. And that allowed them to do a much more thorough analysis and what her bones are telling us is that she lived a really harsh life. She was a teenager probably when she died, possibly falling into this cave that later became submerged. She shows signs of nutritional stress; she had a baby; she seemed to have really strong leg muscles which means maybe she wandered quite a long way. She lived a really harsh life.

Adam Levy: Is there any way at all that we can understand how typical this kind of life might have been?

Ewen Callaway: We should assume Naia was a hunter gatherer like all humans were before 10,000 years ago and even more recently in the Americas. They lived hard lives. They had to find their food. They had to hunt, they had to gather, obviously, given the name. I don't think you'd expect that people would be in pristine health; they lived rough lives. But I think it'll take more human remains discovered from around this time to know whether she was typical. Some researchers have speculated that maybe her malnutrition, her signs of physical stress, were due to climatic changes that were occurring around this time. Maybe the foods that she and her kin were used to eating were less available and it really put a stress on their lives. We really don't know.

Adam Levy: Let's move to our second story which, unlike this first depressing story about Naia's short life, is about the secret – or a secret – to longer life span. There's been quite a bit of fuss for quite a while over young blood.

Ewen Callaway: Yeah, Nature had a Feature out on this, maybe two years ago – let's hope our podcast listeners caught it – but there's these almost spooky experiments that were started in the 1950s where researchers would stitch together the circulatory systems of two rodents, two rats – one young, one old – such that blood from the young rat was circulating into the old and they found under certain conditions that the older rats would live a little bit longer. And researchers who've picked up on these findings a more recently – in the 90s and beyond – have found other health benefits of young blood and they're starting to hopefully identify the molecules that are imparting these benefits. But that's not what I wrote about.

Adam Levy: Young blood is yesterday's news. This week's story is young poo?

Ewen Callaway: The story I wrote about was looking at the gut microbiomes. So the collection of microbes that are in the guts of animals: in this case, fish. One specific fish – a fresh water fish native to Africa called the turquoise killifish. It is among amongst the shortest lived vertebrates in the world. It reaches sexual maturity in 3 weeks, dies in a few months, and it's become a really popular model of ageing. But what these researchers did, getting back to the poop was, they asked the question: are there things in the poop, in the gut microbiota of young killifish that are contributing to healthy aging, that are keeping them young? And so they did really quite a simple experiment. They took the gut contents of a young fish and exposed them to a middle aged fished that had been treated with the antibiotics to clear its gut microbiome. And then they let the fish go on its merry way and they found a substantial longevity boost from receiving the young poop, the young microbe set. I think they were living about 40% longer, so it's suggesting that maybe there's something about the microbiome of a young fish that is helping older fish live longer. What that is, we don't know.

Adam Levy: So the obvious question – and I maybe can already suspect the answer – but would this work on humans?

Ewen Callaway: It might, it might not. It's way too early to test this is what the researchers behind this study told me. I think they'll want to do more follow up studies in killifish to confirm that this effect is real and maybe they might want to do the experiments in larger animals that are more like humans, such as mice. I think that's an obvious experiment. I spoke with some researchers who are interested in doing these experiments and even, even if it pans out in mammals, I'm still not certain that a microbiome transplant is something that people will be doing to live longer. Researchers will probably be more interested in identifying what components of a microbiome are imparting this benefit, if indeed this benefit is real and is caused by the microbiome, so kind of a long way to go.

Adam Levy: So, executive summary: you're definitely not suggesting people try this at home?

Ewen Callaway: I don't think so. That just doesn't seem like a good idea.

Adam Levy: At least until more data comes in.

Ewen Callaway: Have yoghurt.

Adam Levy: Okay, thank you Ewen for joining us. Find those news stories and others of course over at http://nature.com/news.

Kerri Smith: That's all for this week. Come and say hello on social media; we're @naturepodcast. And there's still time to vote for us at the British podcast Awards: http://britishpodcastawards.com/vote. And you can always leave us a review on iTunes.

Adam Levy: Don't forget that the first in our brand new series of round table shows came out on the feed on Monday. These shows are all about the biggest challenges facing science and society. The first is on mental health. I'm Adam Levy.

Kerri Smith: And I'm Kerri Smith.

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