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Interviewer: Shamini Bundell
Hello and welcome to this week’s Nature Podcast. This week, we’re taking a look at electric eel inspired batteries, and virus-inspired shells.
Interviewer: Benjamin Thompson
Plus, an explosive ingredient that could transform volcanic eruptions. This is the Nature Podcastfor December the 14th 2017. I’m Benjamin Thompson.
Interviewer: Shamini Bundell
And I’m Shamini Bundell.
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Interviewer: Shamini Bundell
First up this week, we’ve got a report from Ewen Callaway, who’s been finding out what viruses can teach us about design.
Interviewer: Ewen Callaway
Viruses are studies in symmetry. Their shells are made of repeating proteins that naturally form elegant geometric shapes such as icosahedrons and helices. These shells encase genetic instructions for a virus that lets it infect host cells and make copies of itself. Researchers at the University of Washington in Seattle have been working on designing their own virus-like protein shells that could be used in gene-therapy as an alternative to the real viruses currently used. They’ve now gone one step further and made virus shells that contain the genetic instructions needed to make the shell proteins. And it can be made to adapt to new environments through a form of evolution. I asked Gabe Butterfield why he and his team of protein designers are inspired by viruses.
Interviewee: Gabe Butterfield
We’ve really managed to mimic, initially really before this project even, kind of, the simple structural composition of a virus that is this icosahedral shell. There’s sort of a basic science question about, you know, what does it take to design a viral shell and then what does that shell need to acquire to end up with some of the properties that viruses have? And then on the other hand there’s the application side. We absolutely envision these things as having some biomedical relevance in terms of delivering genetic material to various sites in the body. And so it’s kind of both the basic science and the application side.
Interviewer: Ewen Callaway
And how far have yon gotten in the past in designing virus shells?
Interviewee: Gabe Butterfield
We’ve gotten really pretty good already at the computational design of the shell itself. So really the key design principle is this idea of symmetry and so if you look at the simplest viral capsids you see that they just have a very simple symmetry which you can replicate in the computer and because it’s symmetric, you don’t have to design every single component but rather you design a single interface or maybe two interfaces and that actually just propagates symmetrically and you end up with something that looks like a viral shell. You try, computationally, a large number of protein sequences and basically you then just check which of them can fit to end up with something that actually assembles into a viral shell.
Interviewer: Ewen Callaway
And then do they just assemble by themselves once you have the proteins made?
Interviewee: Gabe Butterfield
All we do is we order DNA, then it codes the proteins we’ve designed and we actually just let bacterial cells to the rest. They do everything from actually synthesizing the protein and then actually once that protein has been synthesized, that’s right, it just self assembles into this viral shell.
Interviewer: Ewen Callaway
Are these viral shells that you’re designing, for lack of a better word, like any other existing viruses out there or are they just completely new to life?
Interviewee: Gabe Butterfield
Yeah, so that’s something that I think that is really interesting is that right, these proteins have absolutely no homology at the sequence level to current viral proteins. Now obviously their shape is absolutely modeled on viral proteins, but these are completely new.
Interviewer: Ewen Callaway
We’ve talked about how you’ve gone about designing these viral shells. How do you make them evolve? Because I think that is what the real breakthrough in this paper.
Interviewee: Gabe Butterfield
We’ve reengineered them relatively slightly such that they encapsulate the MRNA, or you could say the instructions, that encode the shell inside of itself such that it carries with it the instructions for its own construction.
Interviewer: Ewen Callaway
So the fact that the design contains messenger RNA instructions means that you’re able to put it through an evolution like process to actually improve certain traits. What traits were you focused on?
Interviewee: Gabe Butterfield
So the things that we’ve done so far, right, are just improving the ability of this shell to protect that RNA genome and then actually to carry it around in circulation inside of a living mouse and then sort of, the next steps, we’re really trying to move this towards something that could be useful as a delivery tool. So then there’s really a lot more that we need to do in terms of evolving its ability to target particular cell populations. And then once it’s targeted those cells, to release some interesting cargo.
Interviewer: Ewen Callaway
Ah, that’s what I really wanted to understand; is this something that could be useful for gene therapy which I think uses viruses now to deliver genes to cells.
Interviewee: Gabe Butterfield
In the long term we absolutely see this as something that will have some advantages over the typical way that people do gene therapy now with viruses. Because these things are made from scratch, they’re much more engineer-able in general and so one example I like to give is that you can imagine delivering all kinds of other things besides just DNA or RNA – there are all sorts of synthetic analogues of DNA and RNA which you could imagine delivering as well.
Interviewer: Ewen Callaway
So this design is obviously inspired by real world viruses but do you consider this to be a virus?
Interviewee: Gabe Butterfield
Oh, absolutely not. This is not yet a virus in any sense off the word. This is a protein shell which we’ve evolved to have some of the properties that viruses have but it is absolutely not virus. There are many other things that we lack that natural viruses have and the first thing is just sort of a mechanism of getting into cells, a mechanism of actually replicating the genome once you’ve gotten in, and then third of course, some method of getting back out of an infected cell. The idea that we’ve been able to create from scratch even pieces of a viruses I think is just really exciting to people.
Interviewer: Ewen Callaway
What kind of blows my mind is that you’re just looking at a form and doing your own version of it, which I think is very cool.
Interviewee: Gabe Butterfield
You know I think that is one of the exciting things about protein design in general, is that it allows us to build up some of the functions that we see across various domains of life, whether that be viruses, whether that be enzyme functions or anything else. From totally none natural sequences which have never had that function before and then in some cases actually watch what happens when you start evolving from a totally novel starting point.
Interviewer: Shamini Bundell
That was Gabe Butterfield at the University of Washington speaking with reporter Ewen Callaway. For the full study head on over to nature.com/nature.
Interviewer: Benjamin Thompson
The Research Highlights are still to come, where we’ll be learning about wind power’s turbulent future. Next on the show though, I want to talk about how the subtle chemical characteristics of magma can transform volcanic eruptions. Now, I’m no volcanologist; when I think of an eruption I tend to think of the classic cone shaped volcano firing a plume of ash and rock up into the air. Well this isn’t the only type of volcano, but neither is it the only type of eruption… Eruptions can split broadly into two categories. The first are explosive, and they are incredibly violent, ejecting material high into the atmosphere at an astonishing rate. Think of the Mount Saint Helens eruption as an example. The other type is an effusive eruption which sees magma spewing out of a volcano and spilling down the sides as lava, something you might see in Hawaii for instance. The magma inside effusive volcanoes has one major difference to explain its less explosive eruption.
Interviewee: Danilo Di Genova
This magma is in gases so there is no potential for explosions. On the other hand, the magma that is involved in an explosive eruption has a lot of gases under pressure and the release of the pressure is the main force driving the explosion in a volcano.
Interviewer: Benjamin Thompson
This is Danilo Di Genova from the University of Bristol who has led the new research on these different eruptions. He explained the viscosity of the magma is key to where the gas builds up. The more viscous the magma, the more gas gets trapped, with explosive consequences. Danilo has been looking at rhyolitic magma that’s primarily made of a pinky-grey igneous rock called rhyolite. This magma is very viscous and there have been some enormous rhyolite related eruptions. Perhaps the most extreme are the ancient eruptions that happened in Yellow Stone National Park which covered huge parts of western America in ash. However, rhyolite eruptions aren’t always explosive. In fact, they can switch between being explosive and effusive. This change is down to variations in viscosity caused by the make-up of the magma.
Interviewee: Danilo Di Genova
The viscosity is determined by the basic components of the magma and the most important are the silicon and iron content.
Interviewer: Benjamin Thompson
To better understand how the levels of iron oxide and silica can affect viscosity, Danilo and his colleagues mocked up some magma samples. These samples mimic the chemistry of rocks collected from Yellowstone National Park which were formed as ancient lava cooled having been explosively or effusively ejected from a volcano. As melting this manufactured magma requires incredibly high temperatures, it takes some rather special kit to measure the viscosity.
Interviewee: Danilo Di Genova
We have a platinum crucible in the furnace which holds the magma and then we use a spindle made of platinum that is stirred inside the magma and then we measure the resistance to the rotation.
Interviewer: Benjamin Thompson
This is a bit like trying to stir a teaspoon in a jar of honey, except in this case the tea spoon is a platinum spindle and the honey is made out of searing hot magma but either way, the higher the resistance, the higher the viscosity. The team showed that at a particular range, increasing the iron oxide content, while decreasing the silica, results in a more fluid magma. However, once iron oxide content gets above a certain level, things rather turn on their head and the magma becomes extremely sticky. It turns out that when you go over this level, the iron oxide begins to form Nano crystals. Now these Nano crystals cause huge changes in the structure of the magma, although quite why or when they form is something that’s not fully understood but they have recently been found in rocks from real world eruptions.
Interviewee: Danilo Di Genova
What we have found in the last year is that there are many rocks erupted from magma in Italy that have these nanoparticles and these nanoparticles are associated with rocks erupted in an explosive way where actually we expect effusive eruptions.
Interviewer: Benjamin Thompson
Mount Etna, on the Italian island of Sicily is surrounded by towns and cities as are many other volcanoes around the world and Danilo hopes that learning how these volcanoes might erupt in future could be of great help.
Interviewee: Danilo Di Genova
We have found a chemical tipping point for magma and what we can do now is understand how close the volcano is to this tipping point and understand actually if a volcano can erupt effusively, it can erupt explosively in the near future.
Interviewer: Benjamin Thompson
That was Danilo Di Genova there. You can read his paper over at Nature.com/nature
Interviewer: Shamini Bundell
Stay tuned for exciting explanations of electric eels and the News Chat, a story of an acupuncture trial. Now though, we’re joined by Noah Baker for this week’s Research Highlights.
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Interviewer: Noah Baker
If you’re a big fan of wind power, this week’s first Research Highlight could be a bit of a blow. As the planet warms, climate change could disrupt wind patterns around the globe, changing the amount of energy we can generate from wind turbines. A new analysis of how climate change will affect weather patterns shows that wind resources will decrease in northern mid-latitudes of the planet and increase in the southern hemisphere. Knowing which way the wind is blowing will hopefully help us plan for the future by putting turbines in the windiest places. Get blown away by that story over at Nature Geoscience.
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Interviewer: Noah Baker
The Tasmanian Tiger, or thylacine, is a slim, stripy, dog-like Marsupial from Australia, or at least, it was, until humans hunted it to extinction. Now scientists have extracted DNA from a tiny thylacine pup preserved in a jar and have sequenced its genome. Various fun facts have been revealed by combining this new info with other data. One interesting observation was that genetic diversity in thylacines seems to have been declining, even before humans arrived in Australia, possibly due to a cooling of the climate at the time. Another area of interest was looking for DNA clues as to how this marsupial evolved to look so much like the completely unrelated dog family. The protein coding genes in the baby thylacine don’t show the same changes as were thought to have occurred in dog ancestors but further research on regulatory genes could provide some answers. Read more on that over at Nature Ecology & Evolution.
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Interviewer: Shamini Bundell
We love that so many of you listen to the Nature Podcasteach week, but we want to listen to you too! It’s great hearing what you think of the show so do get in touch @NaturePodcast on twitter or email to podcast@nature.com. Huge thanks to Dora Cobrinik for getting in touch to let us know that she still loves the show, even though she misses Kerri Smith!
Interviewer: Benjamin Thompson
Never heard of her. Just kidding, Kerri’s the best, and she has left me some giant shoes to fill. But if you’d like to feed back, and help us reach an even wider audience, then make sure to give us a review or a rating on iTunes or your favourite pod catcher. Every review is like a lovely little wordy Christmas present![Jingle]
Interviewer: Shamini Bundell
Next up, Noah Baker reports on a battery inspired by a fishy friend…
Interviewer: Noah Baker
It seems scientists are always on the hunt for new-fangled ways to generate and store electricity and Michael Mayer from the University of Fribourg in Switzerland is no exception. He and his team’s power plan takes inspiration from one of the natural world’s electrical wonders: the electric knifefish, or electric eel to its friends. Their aim: to make a flexible biocompatible battery which can power anything from pacemakers to wearable tech. I gave Michael a call and he told me all about the electrifying inspiration behind his battery.
Interviewee: Michael Mayer
We’ve been intrigued by this organism really for centuries and this amazing animal that is somehow able, within biological constraints, to generate these very high voltages that can stun prey and also grown humans. I mean, in the very beginning of course when it wasn’t clear exactly what electricity is, the eels actually played a very important role even as a source of electricity that was relatively high magnitude. Of course the other option was lightning which was so big and so dangerous that it was not easy to work with, for all kinds of obvious reasons.
Interviewer: Noah Baker
Can you give me a quick run through about how the electric organ in an electric eel works?
Interviewee: Michael Mayer
Essentially the idea is that water solutions with different salt in them have of course a natural tendency to mix. That’s the overall driving force behind the generation of this bioelectricity and normally this mixing would occur and cause a little bit of heat but really no electricity. But if one places a membrane in between these two solutions and if this membrane lets one sort of ion of salt molecules pass faster than the other, then quickly after putting everything in contact a separation of charge occurs just naturally from the tendency of solutions to mix. And that builds up a charge and that charge is relatively small typically in the order of, let’s say, 150 millivolts, 0.15 volts, but if then many such compartments are put in series just like normal batteries can be put in series then these charges add up and they can reach in eel’s case up to 600 volts.
Interviewer: Noah Baker
And you wanted to take inspiration from that to create your own artificial electric organ.
Interviewee: Michael Mayer
We were intrigued by the idea that you could use chemical energy in the form of the food, for example, that the eel can eat and convert it to very large power output electrically. It would be wonderful if one could somehow, on the fly, generate a voltage or electrical power to drive mobile devices, variables or implantables.
Interviewer: Noah Baker
So tell me, how did you go about replicating it? What was your approach?
Interviewee: Michael Mayer
Right, so the essential things that we wanted to accomplish was to take implantables, solutions of different salt strengths and then we knew of course we needed these selective membranes. Then we would in principle replicate the very basics of what this eel does and the question really was, is this doable?
Interviewer: Noah Baker
And you made these constituent parts – the membranes, the salt solutions, et cetera – from blobs of a material called a hydrogel and they were stacked up in various clever arrays to generate a peak voltage of about 110 volts. Now, that’s pretty impressive but my question is, why do we need these batteries? It seems that we’ve already got pretty good technology for powering our smart phones or medical implants. Why make a new one?
Interviewee: Michael Mayer
Potentially, if all the materials are chosen correctly, such a system could be entirely biocompatible and completely non-toxic. We use hydrogels in contact lenses. Hydrogels are used for wound healing all over the body. They’re also transparent so these could now be all of a sudden a power concept that could be entirely transparent such that one could imagine a biologically powered contact lens that might have a small display integrated and probably the most intriguing aspect of this entire concept is what the eel does so well, which is to be able to recharge inside of biological organisms by converting the energy from food into stored electrical charges.
Interviewer: Noah Baker
Now that is intriguing. That would suggest that potentially could you create a battery that charges itself within our bodies using our own machinery that we already have?
Interviewee: Michael Mayer
This is the wonderful things about bio-inspired research; the eel shows us that in principle, yes, this can be done. Biological systems can generate very substantial electrical power. Can this be done with an engineered material, reliably and reproducibly inside of an organism? I think that remains to be seen but it is such an intriguing question.
Interviewer: Shamini Bundell
That was Michael Mayer from the University of Fribourg in Switzerland talking to Noah Baker. And if you want to see Michael’s battery being made and put through its paces head over to the Nature video YouTube channel where we have just the video for you. Find that at youtube.com/naturevideochannel.
Interviewer: Benjamin Thompson
Time now for this week’s news chat, and we’re joined by Jo Marchant. Hi Jo.
Interviewee: Jo Marchant
Hello.
Interviewer: Benjamin Thompson
Right, first up today then Jo I think I would like to talk about narwhals and as our listeners I’m sure are aware, narwhals are whales with this magnificent unicorn-like horn on their heads.
Interviewee: Jo Marchant
Yes, this is a fascinating story actually. These are quite elusive creatures. There’s an estimated 100 to 150 thousand of them living in Arctic waters around Greenland, Canada, Russia and until now they haven’t really been much affected by human activity. There’s an Inuit hunt where a few of them are killed but otherwise they’ve been left pretty much to their own devices. So this is researchers trying to work out what impact stresses or human threats might have on them and they’ve come up with quite paradoxical results.
Interviewer: Benjamin Thompson
Yeah, and as I understand this news story focuses on narwhals’ heartbeats.
Interviewee: Jo Marchant
Yes, so what the researchers did is, was as they were releasing narwhals that had been rescued, they had been stranded during this hunt or trapped in fishing nets, they attached various recorders to them that were collecting heart rate and dive data so that they could see how the narwhals were responding physiologically and then follow that as they then swam off. They found that weirdly, whereas most animals either have a freeze or a flee response to stress, so they’re either trying to escape as quickly as possible, or they’re freezing, playing dead if you like, the heartbeat is slowing, the narwhals did this strange combination of the two. They were swimming away, diving very quickly but at the same time their heart rate dropped dramatically to just three or four beats per minute and that is really dangerous because they’re using a lot of oxygen when they’re diving and that puts a lot of strain on the heart. The researchers found that in this typical escape dive after rescue from nets or being stranded the narwhals were using up to 97% of their oxygen stores which is really dangerous, compared to just 52% for a normal dive.
Interviewer: Benjamin Thompson
Yeah, if you think about, if you were to hear a loud noise right now, and don’t worry I’m not about to do one, then certainly your heart rate would spike. In humans it’s the classic fight or flight. So this is neither one nor the other then?
Interviewee: Jo Marchant
The researchers just say they don’t seem to have evolved a very healthy response to this kind of threat. So this could be quite dangerous for them if they’re using up a lot of energy to try and get away quickly at the same time as diving and slowing their heart rate, so those two things together is really dangerous.
Interviewer: Benjamin Thompson
It does seem a bit paradoxical and it does seem that usually evolution finds a solution to these sorts of problems. Why have the narwhals not worked out a way to not have this kind of neither fight nor flight response?
Interviewee: Jo Marchant
I think it’s just that these are threats that narwhals haven’t faced before. So we’re talking about human threats coming in, particularly these seismic exploration studies that oil companies are doing. You’ve got this noise, this kind of non-descript threat that’s covering a large amount of the ocean which is simply going to be affecting these animals in a way that they haven’t previously faced.
Interviewer: Benjamin Thompson
Well let’s move on then to our next story. Let’s maybe deep dive into something else now then Jo, and we’re going to talk a little bit about acupuncture and maybe that’s something we don’t often talk about in Nature. What’s going on at the moment in the US?
Interviewee: Jo Marchant
So this is a story about quite a big trial of acupuncture to manage pain in cancer patients. So this is not about using acupuncture to cure the cancer or treat the cancer; this is about managing the side effects of chemotherapy, in particular, a class of cancer drugs called aromatase inhibitors which reduce estrogen levels in patients with breast cancer and these can work really effectively to stop the cancer from recurring but you have to take them for several years, five to ten years, and they cause really serious side effects, particularly pain, which causes a lot of women to then stop taking those drugs. So this is a trial of acupuncture showing that compared to sham or fake acupuncture or no treatment, the therapy actually significantly reduces their pain. And that’s interesting but it’s also very controversial because there are a lot of sceptics out there who really feel that acupuncture is unscientific, magical thinking. There’s absolutely nothing about it that could possibly help patients.
Interviewer: Benjamin Thompson
Maybe before we talk about that debate then, let’s talk about the trial itself. How many people were involved in it?
Interviewee: Jo Marchant
So this was 226 women and one of the interesting things about this trial was that it was a multi-site trial. It was conducted at 11 different cancer centres across the United States. This was several different teams of oncologists who came together to do this trial and the team put a lot of effort into standardizing the treatments that they were testing – both the real acupuncture and the fake acupuncture – because whereas a pin is basically the same wherever you take it, acupuncture can vary depending on who’s giving it to you, so that was one of the things that they really watched in this trial. There was a lot of training to make sure those practitioners were delivering exactly the same treatment in each place.
Interviewer: Benjamin Thompson
When I saw this story the first thing that leapt to my mind was how do you fake having a needle stuck into your arm, hand, wherever you have it stuck. How does one fake that?
Interviewee: Jo Marchant
Yeah that’s interesting isn’t it? It’s not easy but there are several ways of doing it. One is to have retractable needles so it looks as if the needle’s going into your skin but actually it doesn’t. And there are also other techniques like putting the needles in the wrong places, not at acupuncture points for example. Yeah the sham acupuncture that they used had been previously validated in other patients and found to be convincing as a real treatment.
Interviewer: Benjamin Thompson
I suppose that then is a single blind trial in that I don’t know if I’m being stuck with one sort of needle or another. Are some people using this as a stick to maybe beat this work with?
Interviewee: Jo Marchant
Yeah this is the nub of why these trials are so controversial because the gold standard is to have a double blind trial where the patient doesn’t know whether they’re getting the real treatment or the placebo and the person giving it to them doesn’t either because we know that the attitudes and beliefs of somebody who’s giving treatment can actually affect placebo responses and affect how well patients do and of course with acupuncture even if you fool the patient, the therapists still know whether they’re giving the real treatment or the sham. That was the case in this trial so a few sceptics have come out to say, well, this is all fine but you can’t rule out that that was what made the difference.
Interviewer: Benjamin Thompson
Has anyone come out in defense of the trial then?
Interviewee: Jo Marchant
Yeah, so quite a few. So these are oncologists, not particularly acupuncture people who are doing the trial but also some other pain specialists and integrative medicine specialists. Integrative medicine is where complementary therapies are integrated into conventional care in an evidence based way and their point would be that actually there are lots of fields where we don’t have double blind trials – things like palliative care, cognitive behavioural therapy, physical therapy. So the argument would be that well we accept single blind trials in all of these fields so are the sceptics making a special case for acupuncture?
Interviewer: Benjamin Thompson
So clearly two sides to the debate already then. But what has the trial found so far?
Interviewee: Jo Marchant
So in this trial the researchers gave breast cancer patients who were taking these aromatase inhibitors courses of acupuncture and found that after six weeks, their pain was on average one point less on a ten point scale of pain which is statistically significant but not huge and then they also looked at how many patients had a two point reduction in their pain. And here that number almost doubled. It was 58% of the woman who got the true acupuncture compared to just around 30% for the sham acupuncture group and the no treatment group. So that, the researchers say, is a significant difference in terms of a clinically meaningful change for those women. And the hope is that that in the long term could help women to stick to their treatment. That’s something that researchers are looking at now. So, can the acupuncture help more women stay on this life changing treatment?
Interviewer: Benjamin Thompson
Acupunctures been around for hundreds if not thousands of years, I guess, but why this sudden clinical interest in it again?
Interviewee: Jo Marchant
Well one of these reasons that there’s so much interest in it in the US at the moment is because of the crisis over opioid pain killing drugs. So there’s a real epidemic of addiction to opioid pain killers in the US at the moment. So everyone is looking for alternatives to treat chronic pain. We don’t have good solutions for treating chronic pain whether in cancer care or anything else and that’s causing a lot of researchers to look again at acupuncture and say is there something here? And there are some quite interesting studies saying that acupuncture does trigger relevant neuro-physiological changes, so changes in the brain and the central nervous system that are clinically relevant in pain conditions from carpal tunnel syndrome to fibromyalgia for example and then also we’re getting these larger, more rigorous trials now as well. I think researchers, although they haven’t solved all the problems with the trial design, are getting better at testing acupuncture in a rigorous way.
Interviewer: Benjamin Thompson
Thanks for the update there, Jo. Find more on these stories and plenty more over at nature.com/news.
Interviewer: Shamini Bundell
That’s almost it for this week’s show. But before we go, there’s just time to tell you about one of our sister shows, the NatureJobs Podcast. The December episode is out on the 14th, and is jam-packed with handy advice. Find out how lab supervisors can improve relationships with their research staff. Plus, how to show employers that you can learn on the job. Find it on the NatureJobsblog, or wherever you get your podcasts.
Interviewer: Benjamin Thompson
Don’t forget to look out for next week’s holiday show which will feature plenty of festive cheer. I guarantee it’s going to be an absolute cracker. Until then, I’m Benjamin Thompson.
Interviewer: Shamini Bundell
And I’m Shamini Bundell. Thanks for listening.
