Could technology replace animal testing in science?

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Speaker 1 Hello and welcome to BBC Inside Science from the World Service. I'm Tom Whipple.

Speaker 1 Alternatives to animal testing are improving, but will they ever improve enough to have a mouseless lab?

Speaker 1 Also, in a week of beautiful skies in the north and south, Roland Pease has been wondering wondering whether Aurorae are unique to our solar system.

Speaker 1 And why has one Swiss scientist put the last chunks of his favourite glacier in his freezer?

Speaker 1 I'll also be joined by Penny Sachet, managing editor at New Scientist, here for our review of the top scientific journals. Penny, what do you have for us today?

Speaker 3 I've got some new news on how exactly we fall asleep.

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Speaker 1 Well, that's an ambition for tonight for me. But first, in sixteen sixty, Robert Boyle put a mouse in a jar, and started sucking out the air.
Did mice, he wondered, need air? They did.

Speaker 1 Twas not long ere he began to appear sick and giddy, and to stagger, after which he fell down as dead, wrote Boyle. Mice, it transpired, respired.
But fear not, seventeenth century ethics committees.

Speaker 1 Hastily turning the key, we let in some fresh air upon him, by which he recovered, after a while, his senses and his feet as boyle's revived mouse took its first tentative steps mouse kind took its own steps for science last year researchers performed over 1.5 million scientific procedures on mice in the uk alone but for how much longer britain this week unveiled a five-year animal research strategy pledging to create a world where the use of animals in science is eliminated in all but exceptional circumstances new technologies, the government said, put us at a tipping point in the transition to alternative methods.

Speaker 1 But will we ever truly capture the complexity of a biological system without a biological system? With me are Dr.

Speaker 1 Chris Powell, Director of Cambridge Biopharma Consultants Limited and honorary visiting scientist at Cambridge University. Hello, Chris.
Hello.

Speaker 1 And Dr. Natalie Burden, head of new approach methodologies at the National Centre for the Three R's.
Hi, Natalie. Hello.
Hello.

Speaker 1 Now Natalie let's begin with the three R's, something that certainly lab scientists listening will know about but for the rest of us what do they stand for?

Speaker 6 So the three R's are the replacement, reduction and refinement of the use of animals in research.

Speaker 1 It's particularly two of those R's that we're interested in today, the reduction and replacement.

Speaker 1 The government says we're now at a tipping point with new technologies that can maybe bring us away from using quite so many animals. What are those technologies?

Speaker 6 Things like organoids, which are 3D recapitulations of organs, so where we take cells and we're able to grow them in the lab in a 3D structure that actually really well mimics the structure and the functioning of those organs.

Speaker 6 As well as that, we have organs on chips, which

Speaker 6 sounds a bit strange, but essentially what we're talking about here, it means that we can look at how drugs might be able to be moved around the cell.

Speaker 6 We're also talking about some of the very sophisticated computational models, so looking towards how we can better implement aspects such as artificial intelligence in our research.

Speaker 1 Chris, you all have had in your career a lot of experience of using animals. Where currently are animals tested on and for what?

Speaker 7 In the pharmaceutical industry, animals are tested in the first phase of drug discovery, where you're trying to find the right molecule or protein or antibody that you think will have therapeutic potential.

Speaker 7 And then in the second phase which is development

Speaker 7 there is increasing use of computational methods and the sort of complex in vitro methods but there are some biological effects

Speaker 7 which at the moment we're not able to identify except by using live animals and so some of those tests are conducted as part of the the so-called development phase.

Speaker 1 Natalie, how good are these technologies now and are they already replacing animals?

Speaker 6 Depending on which area of science you're looking at, we've got different levels of maturity of the approaches, but certainly we do have real-life examples now where we're starting to be able to see some of these approaches being used in practice.

Speaker 6 Some work that the National Centre for the Three Rs has funded previously has established some methods such as retinal organoids, so looking at the structure of the retina at the back of the eye.

Speaker 6 And what that has done is essentially taken donated cells from either patient samples or from human donors and use organoid technology to essentially recreate a human retina that contains all the different cell types that you might find within the human retina.

Speaker 6 And then we can actually look then to test drugs that are intended to treat eye diseases to see firstly, do they cause any toxic effects?

Speaker 6 Secondly, can they be more effective in terms of treating these types of diseases? So, this is an area where we actually have the methodology ready.

Speaker 6 It's already been commercialised by the company that develops it and it is already being used in-house by the pharmaceutical industry.

Speaker 1 Chris, last year there were 2.6 million procedures performed on animals in research in the UK. Two-thirds of those were on rats and mice, but almost 2,000 were on primates.

Speaker 1 And it's UK law this can only be done if this is the only option. Why is it still? the only option?

Speaker 1 When do you think we just have to go into an animal and why?

Speaker 7 I think for some medicines, particularly I'm thinking of humanized antibodies or some other advanced therapies,

Speaker 7 they are really not compatible with the immune responses that you would see in any animal other than a primate. And of course, because

Speaker 7 primates are our nearest relatives, although their immune function is not the same as human, they're closer.

Speaker 7 So if you want to understand whether a new antibody has some potential to cause adverse effects, in some instances it's recognized, at least at the moment with the current technology, that studying a primate is probably the best option to try and identify any serious or irreversible harms that might happen when that antibody was first given to a human.

Speaker 1 And why can't artificial mechanisms currently replicate that?

Speaker 7 Well, I suppose one of the reasons that we have to use animals is that there are some circumstances,

Speaker 7 such as the potential for a drug to affect fetal development, where for all sorts of historic reasons there is great sensitivity and a very strong desire to avoid irreversible effects.

Speaker 7 So at the moment we don't have in vitro or computational methods that can replicate the complexity of embryo fetal development.

Speaker 1 A question for both of you, but I'll start with Natalie. The government's made it pretty clear that the goal is getting close to the elimination of animal testing.
Can you see that happening?

Speaker 6 We're certainly seeing an acceleration towards that.

Speaker 6 And we are seeing a convergence, as you say, in the scientific advances, as well as the technological capability and then the political will that's bringing all of those things together towards a tipping point where we're going to be looking towards that as the future.

Speaker 1 Chris, can we retire the lab mouse?

Speaker 7 I don't think there's any immediate prospect of it. But one particular point that I think some people are not as aware of as they could be.

Speaker 7 Many who are uncomfortable with animal experiments ask, why can't we simply test new medicines on cells in culture and then in humans and patients?

Speaker 7 And of course, that is the goal, but there are some examples. For instance, veterinary medicines,

Speaker 7 which includes medicines to treat dogs and cats and horses,

Speaker 7 in the particular case of developing those, animals are the patient.

Speaker 7 So testing new veterinary medicines to show that they work are animal experiments, and I don't think there is any foreseeable means of

Speaker 7 phasing out or reducing those experiments in the future.

Speaker 1 Dr. Chris Powell and Dr.
Natalie Burden, thank you very much. A reminder, you're listening to BBC Inside Science on the World's Service.

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Speaker 1 Here's Roland Pease.

Speaker 1 Millions of people have been enjoying spectacular Rory this week. Though not me here, it's been permanently clouded.

Speaker 1 But from as far south as Colorado in the States and from France, I've seen pictures of the dazzling nightlights and from as far north in the southern hemisphere as Sydney, Australia.

Speaker 1 The colour fill displays are the product of solar outbursts, coronal mass ejections, whose energy gets channeled normally to the north and south pole, except when they're particularly energetic.

Speaker 1 And I had assumed every star, or at least many, would undergo the same same kind of violent eruption. And so too hood astronomers.

Speaker 1 But it's only this week we have proof, thanks to a European radio telescope network and a team led by Joe Cullingham of the Netherlands Institute for Radio Astronomy.

Speaker 1 You may have heard about these beautiful auroras. These are caused by the impact of a coronal mass ejection or a stellar storm on the Earth.

Speaker 1 And so in the sun, there's all types of magnetic fields and they can cause kind of superheated plasma.

Speaker 1 A very hot gas gets spilled into interplanetary space And that impacts the Earth and drives these aurora. So it's this ball of plasma that sort of detached itself.

Speaker 1 It's been thrown out from the outer parts of the sun and races through. And sometimes they go in completely different directions.

Speaker 1 But when they hit us, that's when we see the aurorae and the satellites may get a bit fried or something. Yeah, exactly.
And in some really extreme cases, yeah, it can knock out telecommunications.

Speaker 1 Now, you're seeing this not from the sun. But you're seeing something pretty similar coming from a star somewhere in the galaxy, and that's news.

Speaker 1 Yeah, so for a long time, we understand the sun can emit coronal mass ejections, but how do we find that?

Speaker 1 Well, what we do is we try to block the really bright part of the sun, you know, the photosphere, which you can see with your eye.

Speaker 1 Obviously, don't look outside with your eye, but you can see it with your eye.

Speaker 1 We block that, and you can see this plasma moving away from it. But we can't do that with stars.
Stars are too far away. We don't have the resolution, they're just too distant.

Speaker 1 And so, we're left with using traces. And for this study, we used radio emission.

Speaker 1 So, we know from the sun when a coronal mass ejection happens you get a very characteristic radio burst and that's what we hunted for from other stars what's this radio emission coming from this is coming as it were from this ball of plasma this coronal mass ejection yeah exactly so as this coronal mass ejection comes spilling out it's moving so fast relative to the other gas around it that it emits radio emission.

Speaker 1 And so it's a shock front, more or less, kind of like a ship moving through ocean. It's kind of...
You're a sonic boom. You're a sonic boom, exactly.
Yeah.

Speaker 1 And so that drives radio emission uh really bright in the radio and we discovered this uh radio astronomers in the 40s and 50s i mean the early days of radio astronomy so the idea of trying to hunt for these from other stars these are poetically named type two bursts you know because radio astronomers have great imagination that's been around for a long time but what's changed now is we've got the sensitive enough telescopes this telescope called lofar which is situated in the netherlands but spread out all over europe and we used a novel process a new process developed by some of my french colleagues to try and search for these bursts from the stars.

Speaker 1 Just because I'm slightly confused.

Speaker 1 I have spoken to other astronomers in the past about what they call stellar flares, which are sudden brightenings, which have always sounded a bit like one of these solar storms.

Speaker 1 I mean, is this a different thing? Or is it that all you know is that's brightened. You don't know if something's been thrown out.

Speaker 1 And this is sort of the first proof that you've seen this thing emerging, being born, as it were, out of a star. Yeah, you hit the nail on the head, Roland.

Speaker 1 So we've known for a very long time that stars flare all the time in optical, and they can get very bright, particularly these end dwarfs or these red dwarfs that we study at the moment and a lot of people interested in.

Speaker 1 These are about 10% to 50% of the mass of the sun, so they're smaller. These flare, like they can get 10 times brighter than the quiescent flux.

Speaker 1 You know, if imagine if the sun all of a sudden got 10 times brighter during the day, it would be pretty freaky. Kind of like the opposite of a total eclipse, right?

Speaker 1 So we know these stars do freaky flares, but we really didn't have an idea if there was really mass loss occurring.

Speaker 1 Maybe they flare and this blob of gas gets trapped in what's called the magnetosphere, which you can imagine a bubble around the Sun and it just stays there. It never hits a putative planet around it.

Speaker 1 So maybe that's okay.

Speaker 1 And so what's interesting about our study, where this really changes the game, is that the only way to get a radio burst that we've seen is if it's become disconnected from the star, because that shock front won't form unless it's left the star completely.

Speaker 1 And so while we're getting that radiation as it's pushing through, you know, just the interplanetary gas or something like that. Exactly.

Speaker 1 That's the trick that's a trick yeah and you've associated it have you with a particular star yeah a very boring another again another poetically named star STKM1-1262 you practice that I hope I got it right.

Speaker 1 It's a boring old M-dwarf, so about 50% of the mass of the Sun, but it's a bit more active. It rotates much faster around once a day, so that's pretty fast.

Speaker 1 It rotates about the same speed as the Earth, but it's much bigger than the Earth. And it's quite hot.

Speaker 1 I mean, and did you see this by accident, or was there a reason to be looking at this particular star or we we searched so many stars rolling i can't describe how many stars we searched well i can 100 000 stars we looked at to try and find this burst and we only really found it from this one this bright characteristic boat we got very lucky okay so the big questions are one

Speaker 1 this particular star do you know if there are planets there in other words i'm wondering if there might be aurori as well as this coronal burst yeah so for this star itself we don't know it's just turned out to be a random star but i know some of my optical colleagues are now hunting it with traditional exoplanet searching to see if there is one.

Speaker 1 But just to say, we know pretty much now that almost every star in the galaxy has at least one planet, which is an amazing statement to say.

Speaker 1 So what's amazing about this study is we can say, well, what does that look like for planets around stars that look like this one? You know, or maybe this one has a planet itself.

Speaker 1 It's kind of like a piece of a really complex puzzle of like, how do we find a habitable planet?

Speaker 1 And understanding how often these coronal mass ejection occur is one of those important pieces in that broad problem. Because, well, this is my next question.

Speaker 1 Was this blast like the thought that we're getting and these pretty auroras that we're seeing? Or was it the kind of blast that could actually toast a planet?

Speaker 1 Yeah, I don't think you'd want to be on the planet's surface. Maybe you'd have a great auroral display, but it's not going to be a very enjoyable place to be.

Speaker 1 I have a colleague that describes the planets around these types of stars, these M dwarfs, red dwarfs, as Godforsaken planets, you know, and this study is kind of confirming it.

Speaker 1 The CME that would hit it is about a thousand times stronger than anything we've seen before from the sun.

Speaker 1 That does not bode well for a planet because it's so strong, it can actually compress a magnetic field like the Earth's to the surface. So the Earth has a magnetic field.

Speaker 1 That's why you see the aurora we have because it funnels those high-energy electrons to the poles. And this kind of protects the atmosphere of the Earth.

Speaker 1 But if you have something too strong, that could compress the magnetic field.

Speaker 1 And now the atmosphere is fully exposed to those particles, that gas, that blob of gas, and that can strip away the atmosphere. So, great, guess what?

Speaker 1 You found a planet, it exists in the perfect location in terms of the Goldilocks zone, such that liquid water can exist on the surface. But now, the star is not a good host.

Speaker 1 It hits it with so often with these CMEs that you've got no atmosphere, and so you look like Mars and you don't look like Earth. No, dear.

Speaker 1 And Joe Cullingham's hope is the more sensitive and accurate square kilometer array that's currently being built will show whether other sun-like stars also have aurora potential.

Speaker 1 Go to nature.com for more on the outburst at STKM1126.

Speaker 1 You know what I mean. Thanks, Roland.
A valiant effort. Down here on Earth, when does a glacier die? Is it when it stops flowing? Is it when the last bit of ice melts into the last alpine stream?

Speaker 1 Or is it, at least in one very specific instance, when Matthias Hus's wife tells him that she wants her freezer drawback.

Speaker 10 This is probably one of the last remnants of my pitshall glacier.

Speaker 10 It's not for science that we're doing it, but it's just for keeping a memory of this glacier that has meanwhile disappeared or almost completely disappeared.

Speaker 1 Hus is a world expert on Swiss ice. As leaders gather for the climate conference in Brazil, his research has become one of the more powerful tales of a warming world.

Speaker 1 In the past decade, data from Hoos has shown a quarter of Swiss ice has been lost. In one year alone, in 2022, 6% disappeared.
Hundreds of glaciers have been lost entirely.

Speaker 1 But one of those glaciers remains in his basement next to the frozen peas.

Speaker 10 Yeah, so I'm taking out this big chunk of ice and must say it's pretty heavy. So I would say it's maybe, well, three,

Speaker 10 three kilograms or even four kilograms.

Speaker 10 it's about the size of your head i think and it's sort of cloudy it's it's glacier ice it's got lots of bubbles in i guess yes and there's still some some debris on it that was frozen into when we took it off from the glacier and it feels special holding it in my hand and it's precious it's emotionally precious for you as well this is your glacier isn't it yes and i mean this this mission that we did two years ago to rescue this ice it was really just for getting down this ice and this was pretty special having this piece of pits all in my freezer because at the moment the glacier is always completely gone.

Speaker 10 So I've been up there again this summer, but it wouldn't have been possible to rescue any ice.

Speaker 1 Explain Pitzel's place in your academic career.

Speaker 10 Pitzol Glacier is quite close to where I live. It has been a very small glacier all the time.

Speaker 10 been there as a child for the first time, I think, and we've

Speaker 10 just admired this small glacier because it was beautiful and when I started with my PhD thesis I kind of selected this glacier for my own personal studies and this then grew into a proper monitoring program that I followed up also with scientific works until 2022 when we needed to stop the measurements.

Speaker 1 And you stopped because there wasn't enough to measure.

Speaker 10 Yes, so the glacier started to fall apart after 2018 and then there were still some chunks of ice where we could place our poles for measuring the melting but then in 2021 we realized that it's just not working out anymore and with the extreme year of 22 that was record shattering all over the alps the glacier kind of shrunk so much that almost nothing was left and what was left was covered by by rock debris um and so one one moment do you still need me in front of my freezer because because otherwise i would quickly put back the ice into the freezer we we don't want the pitzel to to melt to melt away exactly so i'm a bit bit anxious so i want to no put it back in the freezer in your 20 years of studying glaciers what's happened to them in the alps in those 20 years they have strongly declined it's really incredible um we just calculated that just in the last decade they have lost one quarter of their ice volume in switzerland and some of the small glaciers they have completely vanished the bigger ones have just become smaller but it's it's really difficult to imagine how much has changed in these last 20 years and on the other hand it's also an issue for natural hazards we have very impressively seen this this may um this glacier collapsing in uh the luchenthal bearing the village of blatten and these are events that seem to be becoming more frequent as well with climate change.

Speaker 10 There is always many factors that are combined to cause such a big disaster. But still, with the decline of glaciers, with the thaw, permafrost, the Alps are becoming more unstable.

Speaker 1 All the world's leaders are now in Brazil. Well, not all of them.
There's one notably missing. But they're talking about climate change.
What do you hope will come out of this?

Speaker 10 These conferences, they happen year and year again since 30 years now and uh

Speaker 10 the knowledge bases has been the same since the beginning so we are scientists we are providing the data we are demonstrating what is happening the science is all clear about it and i think many of the world's leaders have meanwhile also realized that it's time to act

Speaker 10 but the problem is really how to implement it because it is really difficult to find a solution where everybody agrees because nobody wants to limit their own economy.

Speaker 1 For glaciers in Switzerland, if you've already lost a quarter of the ice in the past 10 years, if a miracle happens and we manage to limit warming to two degrees, what does that mean for glaciers when they finally stabilize with that?

Speaker 10 Well, for Swiss glaciers, it's almost too late already. So even if we manage to limit warming at the global scale to two degrees, we will be losing about 80%

Speaker 10 of the remaining volume that we have now. So we could only save a little small remnant in the biggest glaciers while almost all of the smaller glaciers would disappear anyway.

Speaker 10 But it would of course mean that we have still some eyes to show to our children and grandchildren.

Speaker 1 That was Matthias Huss from ETH Zurich. Now, Penny Sashet is here from New Scientist.
Every week we review the pick of the latest papers. So my paper that I've I've spotted this week is in bees.

Speaker 1 It's about teaching bees Morse code or we can see that bees can learn Morse code. So this is from Queen Mary University of London.

Speaker 1 They've showed some of the bees that they've been shown these flashing lights, either sort of long dashes like in Morse code or short dots

Speaker 1 and they got to associate them with tasty food or unpleasant food and what they showed is that they could train the bees and they could distinguish short dots from long dashes.

Speaker 1 Now why?

Speaker 1 And the reason why this shows that there's some reason why bees need to worry about duration of things going on and this might be to do with the waggle dances where they need to know the rhythm of the dances but it's yet another sort of chink in our understanding of how clever bees are.

Speaker 3 Because they are phenomenal aren't they? We know that they can do all kinds of maths, they understand the concept of zero, they can do basic arithmetic.

Speaker 3 I'm struggling to understand why they need to know short versus long.

Speaker 1 Why is temporality? Yes, and actually, I'm going to come in there because the favourite, my favorite intro to a news article ever came from Oliver Moody at the time.

Speaker 1 He was writing about the bees counting, which is also Queen Mary research. I think they can count up to about four.
And it was

Speaker 1 two bees or not two B's.

Speaker 1 That's a question you can ask a B.

Speaker 1 Let's move on. I can't follow that up.
That's a good line.

Speaker 1 What else have you got?

Speaker 3 So this one is about how do we fall asleep. So my colleague Grace Wade reported on this for us.
It was in Nature and Neuroscience. And I thought this was very interesting.

Speaker 3 I mean, everyone's obsessed with how they fall asleep, right? And it was thought that we gradually descend into sleep.

Speaker 3 One classical idea was that there's sort of nine levels of brain activity that you slowly move down through before you go to sleep.

Speaker 3 But this new study suggests that it's actually far more sudden than that, and I think that's really interesting.

Speaker 3 So, what they did was they developed a technique for mapping EEG activity, brain activity as measured by EEG, in various volunteers as they were trying to get to sleep and falling asleep.

Speaker 3 And they did a clever sort of thing where they kind of mapped out these different, the different readings of brain activity they had in a sort of space where you could then measure for each person how far are they from the sleep zone, which sounds lovely.

Speaker 3 They found there is sort of two phases, really.

Speaker 3 You're kind of nowhere near the sleep zone, and then on average, but it does vary, around 10 minutes before you fall asleep, you get closer to the sleep zone.

Speaker 3 And then about four and a half minutes before you fall asleep, there's this tipping point, which is like a point of no return. And once you're kind of down that line, you are falling asleep.

Speaker 3 It isn't this kind of gradual descent. You're trying to get to that point where you can flick that switch and it almost feels like it explains that feeling of falling asleep.

Speaker 1 It's fascinating that this is such a basic thing. Yes, yeah.
We all do this, it's really important to us, but we I mean we basically, there's not even consensus on why we sleep, is there?

Speaker 3 Yeah I mean a lot seems to be to do with memory consolidation and then increasingly we're learning that there's a lot of clearing out the junk from the brain

Speaker 3 but so much of this is still actually quite new.

Speaker 1 Well, look, I know that people sometimes, heaven forbid, use the radio to fall asleep.

Speaker 1 I hope that everyone's managed to keep away from that switch until the final last minutes of Inside Science because that is it from us. Until next week, it is goodbye from me and goodbye from Penny.

Speaker 1 Goodbye. It was produced by Claire Salisbury.
Technical production was by Mike Mallon.

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