A brand-new colour created by lasers, a pig-liver transplant trial gets the green light, and a nugget-sized chunk of lab-grown meat
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Hi listeners, Benjamin here. As is tradition around this time of year, we're going to do something a little bit different on The Nature Podcast this week. We're going to do a deep dive into some of the stories that have been in The Nature Briefing. And joining me to do so is a crack team of science journalists. We've got Sharmini Bundel. Sharmini, how are you doing today? Hey, doing great.

Excellent. And Lizzie Gibney. Lizzie, hello. Hello, Ben. Thanks for having me. So three stories to talk about today. Let's go with one, Lizzie, that you've been covering for Nature. And it's a story about a new colour. It is. And I think this is amazing because it's all about how your brain actually interprets colour, which I don't think I really had fully comprehended before I wrote this story. Cloth.

colour is all a bit of illusion is my takeaway from this. But it's a new colour, it's a kind of bluey greenish colour but by definition we can't quite describe what it is with words or even to show you because you only see it under very very specific conditions. But yeah five people, five participants in the study have been the only ones in the world ever as far as we can tell to see this colour which is a very very intense vibrant they call it saturated bluey green.

Yeah, this is a slight change for you from all the physics because yes, obviously how we see colour depends on the cells in our eyes and that's kind of how they've made the new colour, isn't it? With the cells in your eyes. Exactly. So it involves light. So that is definitely in my wheelhouse. Light and photons. Yes, thank you. But no, it is all about cells. So the way that we see colour, okay, is you have three of these different light receptor cell in the eye and these are called cones and they all see a different range of wavelengths of light, but those ranges overlap each other.

So what happens is when you see one color, you get a color coming in, your brain actually is getting three different numbers. It's getting how much does each of those cones fire? And it's almost like those numbers, the cones don't care what color they're seeing. They just know I've zinged this much. And it's putting all of those together that your brain goes, OK, I know that I'm going to call that color whatever it is. So what they did here was, first of all, they mapped all of those cone cells in the participant's retina.

and they got this motion tracking technology so they could not only see exactly what the map of cones was on the back of their eye but they could label them these three different cone types and they could track them and follow them and then they could target them with lasers

So using this, they could do something that I had never seen before. So at the very far ends of the spectrum, if it's very red or very blue, you might have just one of those cones firing, the other two are silent and the brain knows how to interpret that. But in this middle, this kind of greenish region,

There is never a case where that would fire on its own because you'd always get one of the other two types of cone firing as well. So what they did here was they fired only at those middle region cones and the brain was seeing a kind of signal it had literally never seen before and that produced this unprecedented colour. So all it required was having lasers strapped to your face in order to see a type of green? Yeah.

It's also, I should say, it's a really tiny little bit of your vision. So if you were looking up in the night sky, it's about twice the diameter of the moon as you would see it in the night sky. It's that little part of your vision that they've been able to change. And it does take a lot of technology. Not only do you have to have that mapping done, which is quite intensive, but then you have to be in a lab where you have this ability to fire these little tiny microdoses of lasers at

at your eyes. But there are very good reasons for doing it, not just to make this very cool colour. Yeah, I was going to ask you, does this have any practical applications? Because you've written an article about this for Nature.

nobody can see this color apart from these five people there must be more to it yeah totally so there are a few things so one is just the pure research angle right like we don't fully understand how your brain interprets that signal as i say you get like three different almost like you could just consider numbers like zaps of intensity and it translates that into a color now that itself is fascinating and these kind of studies will help us figure out how the brain does that

There are also potentially some more practical and medical applications for this. So colorblindness, the most common type of colorblindness involves people having only two of those cones. So as I said, people normally have three. In the red-green colorblindness, you only have two. So what they can do using this technique is pick a subset of those cones. So they only have the two types, but they pick out some of them scattered across the retina and they decide to artificially make them like a third type.

so you can train the laser on them and you give it exactly the right intensity of light to make it a distinct category from the other two. So each one of those of that type will be seeing exactly the same and they'll go up and down in the same way and effectively you give your brain back its three channels that it's used to having in order to create colour. So where before you just had two lots of input from the two cones, now you've got the two real cone cells plus one artificial lot of cone cells.

And so the idea is that that could potentially restore full colour to people who are colourblind right now. I think my favourite thing about this story is just that there's like a new colour that no one's ever seen before, partly because colours are fake and it only depends on which cell is firing in your eye. But then they've given it a name and then they've tried to sort of show people and explain what colour it is, which is kind of nice. Yeah, it's called Olo or Olo. Yeah. And so the way that they also...

determined that they definitely were seeing a new colour because that would be a fair question, like how did they do it? How can you judge that? So they showed them lots of light of a single wavelength, monochromatic light, and they tried to get it to match up which one it was most like. Now it didn't match any of them, but the way that they could get it to match was by getting participants, they were allowed to add in as much white light as they needed to make it look like the real colour that they could see or the natural colour that is normally in the kind of colour palette that a person would have.

So in order to make it match with a natural colour, they had to add lots of white into the colour that they have already. So if you can imagine the real world that we see it, if we could see all colours like this, would be like a pastel version, like a washed out version of what you could see with this kind of new colour. So that's why I say it's like really kind of off the charts, intense, literally off the charts.

an intense bluey green we'll have to make do with seeing the normal apparently faded and dull bluey green that we have in the real world until we obviously can get you know maybe some sort of setup to fire lasers in our eyes that is the thing it involves a big old setup you have to have the scanning you need the lasers if it was to actually be some kind of cure for color blindness you'd need a way for it to take the real world as input i guess some kind of oh

augmented reality and then do the calculations to translate what that should be in terms of lasers, you know, micro doses on all the different cones and then you'd have to have a way of making your laser somehow teeny tiny and not just built in that lab. So it's a long way off. But you could imagine like having a display...

So people with colour blindness might have, you know, in front of them a display where they could for the first time ever see all the colours. You just like hold it up and be able to see things. That's very cool. And Lizzie, what are the researchers saying about this? Because on the face of it, this is quite a fun thing. What are other people saying about it as well? Yeah, people told me it's just it's an extraordinary achievement and that technically it's very, very difficult. It's

pretty much only this lab. So it was at University of California, Berkeley, working with University of Washington. And it's that Washington lab where they have this ability to scan and track and

It's kind of not available anywhere else. So the interpretation is this is technologically really quite impressive. And they were also very convinced by the idea that this was a new color. They did other tests where they had the color as like a line on a background and then they wobbled the laser. And if you wobble the laser, it's not just going to your middle cones anymore. It's going to all of the cones and the line just disappears. Oh, wow.

So again, they really quite conclusively showed that people were seeing a new colour, which is, you know, otherwise you could imagine quite a tricky thing to do. So researchers thought, even if it doesn't turn out to be anything in terms of a cure for colour blindness or another application in that way, just as a bit of research about understanding our eyes and how our brain works,

comes up with this incredible array of colours that we see. Yeah, they said it was impressive. Well, to read more about that, and sadly not to see it, unless you have lasers pointing at your eyes, in a safe lab environment, head over to nature.com to check that out. But let's keep going in today's list of stories that have been covered in the Nature Briefing. Sharmini, what have you got for us this time?

Yeah, I've got another sort of technological advancement aiming to have some really important practical applications, actually. This is about xenotransplantation, the transplantation of organs from pigs, generally, it could be any animal, but pigs is the one that people look at,

the US Food and Drug Administration has just approved a trial for pig livers to be used for people with liver failure. It's not actually going to be a transplant. It's going to be pig livers used externally on these people. And it kind of comes after an approval of a trial for kidney transplantation. And after quite a long

time of experimentation in this xenotransplantation field. Well, we've covered xenotransplants a few times on the podcast because there's a critical need for organs for transplantation. Tell us about this trial then, Sharmilee. The idea of this one is it's specifically aimed at people with a very serious form of liver failure, which has a mortality rate of about 50%.

And there are four people who will be in this initial phase of the trial, all of whom have acute on chronic liver failure. So it's when you have a chronic liver disease that suddenly worsens and a brain disorder caused by impaired liver function. And this is going to be the first time that it's a trial with multiple people. They're going to start off with two, do some safety checks, then three.

the second two and then if that goes well they want to expand that out they have done initial sort of experiment with this before in 2023 a man in america who was clinically dead was connected to a pig liver and both in that case and in this trial these are livers outside the body so the idea is that when you have liver failure there is this buildup of harmful waste in the blood

So if the blood can be routed via this external liver, it can be sort of cleaned essentially and then put back in.

And with these four patients, what they're hoping is that this cleaning of the blood will give their livers time to recover a bit. And I should say that these are all four people who aren't, for whatever reason, eligible for human liver transplants, which would obviously be the ideal. But the shortages of human transplant organs is why everyone is very interested and has been for some time in transplants.

trying to work with pig organs. Yeah, I guess you've got to be in quite a dire situation in terms of health to be eligible for a trial like this as well, because it is so experimental. Absolutely. And so far, there have been not trials, but individual experiments where they've put various different organs from pigs into people. And they've all been specifically approved on compassionate grounds.

by the US FDA, for example, because it is people who are dying. And in most cases, those people haven't lived terribly long. But them doing that has been hugely important for the study of, for example, how do we stop the human body rejecting the pig organs? And these are all genetically modified pigs. So the big question is,

Which genes do you need to change? What kind of genetic modification do you need to do to stop organ rejection by the human body and to avoid viruses and things like that, which has also been an issue? Right. When I talked with our colleague Max Kozlov about implanting pig kidneys into non-human primates, a big part of that was trying to remove viruses that are found inside pig genitalia.

that can reawaken upon transplantation. Yeah, that's definitely been an issue as well, yeah. So this genetic modification of the pig, so that's something that's ongoing then, is it trying to figure out kind of exactly the right genes that you need to alter in order to have a liver that is compatible? I think different groups are experimenting with different modifications, different number of modifications. And it's quite hard to test this out because there is a lot of testing on primates,

But putting a pig liver in a baboon, say, is completely different. What you need to do is to work out how it's going to work in humans. And as you say, it's quite an extreme step. You have to have quite specific circumstances to be able to do this.

But yeah, we are now finally getting the go ahead from the FDA for actual trials. So this is a really significant step forward. And what's the timeline then for how this proceeds, Sharmini? So this trial with external pig livers and also the trial that was also approved recently with kidneys are both due to begin later this year. And for this liver trial, there will basically be a two week period in which the participants will be connected, not continuously, but for a total of 72 hours, they'll be hooked up

to this pig liver and the blood will be going through the pig liver and then they will be monitored for a year to see if there's been any changes, see the safety of that procedure. Hopefully that will keep those people alive. Maybe the livers regain some function and then the researchers will be able to see after a year and then maybe expand this trial. I guess that's it. The hope is it's taken a really long time to get to this point, but it's

it will be able to accelerate once there are more compatible livers and there's more proof of safety, you'll be able to do bigger trials and you'll get more funding. But it might also then throw up the new problems that we haven't seen before, particularly infections and organ rejection. And so it might then also be a matter of finding a new problem and then going back to the genetic modification drawing board to then solve that problem. Well, thank you for laying out the timeline then. We've covered this story a fair bit and I'm sure we will continue to do so. There is...

some through lines to the story that I've got, which on the face of it is a fun one, but we'll unpick that a little bit towards the end. Now, my story is also something we've been keeping an eye on here at Nature, and it's about lab-grown meat. And the reason that I picked this story to talk about is there is an absolutely incredible headline over at nature.com slash news. Yeah.

And part of the headline is winner, winner, lab made dinner. And it's a story based on a trends in biology paper. And it's about growing a small lump of meat, of chicken, to be precise, which could be potentially a big step forward for this endeavor to create more lab grown meat. So what's the kind of state of play at the moment? Because I've heard about people growing meat in labs, you know, for people who don't want to eat meat.

and for people who want to think about the environment and find other ways of getting protein. But what stage have we been at before now then? Yeah, lab-grown meat is available and you can buy it in some countries. Here in the UK, it is approved for use in some pet food, for example. But there are products that are available for human consumption too. But the meat created in a lot of these efforts, really, it's only tiny pieces of meat.

And what happens is these are sometimes grown on a scaffold or they're stuck together with edible glue. In one example, they're 3D printed kind of fat cells and muscle cells to create this larger structure. But if you want an actual plant,

chunk, an actual piece of meat. That's what some people are looking to do. And it's desirable because it helps mimic the structure and the texture of meat that it's trying to emulate. And that's been really, really hard to do because cells, when they're growing, they need a lot of oxygen. They need a lot of nutrients. And in physiology, that's what blood vessels are for, right? They're really good at delivering oxygen and nutrients and all the rest of it to the places that that needs to be done.

And recreating this has been a real challenge in this field. And that's what a team appeared to have done in this instance. They've designed a way of growing cells, but also perfusing them, I think is the right word, with the things that they need. And their setup, well, it seems quite simple on the face of it. It is kind of two blocks and stretched between them are lots and lots of fibres. Now, these are semi-permeable hollow fibres.

And they're the type used in household water filters and in kidney dialysis machines. Now, there's a picture of this in the article. You can see it for yourself. We'll put a link in the show notes. And these semi-hollow fibers do exactly the job of blood vessels, right? They provide oxygen. They provide nutrients. They take waste away. And it's enabled this team to grow a small chunk of blood.

But much bigger than the chunks we had before. Much bigger than the chunks we had before. The measurements are seven centimetres long, four centimetres wide, two and a quarter centimetres thick, 11 grams. For those of you trying to keep score at home, it's about the size of a chicken nugget. So when we're talking about like it's lab grown meat, here is some chicken. We're talking about chicken muscle cells.

And the challenge is to get them to survive, sort of stick together, grow as a muscular chunk. And that's what all these tubes are providing all of that right into the depths of the nugget, the oxygen and the nutrients. That's right. But it is worth saying that these fibres aren't edible and need to be removed by hand currently. But the team are working to maybe automate this process or even replace the tubes with something edible, which could further mimic the characteristics.

the kind of structure of meat. But of course, there are a multitude of hurdles before that comes to pass. Right, so this hasn't been made with food grade materials. And apparently the team hasn't tasted this meat, which was my first question. But issues involved in

You know, if you want something bigger, you need more oxygen. So you need more fake vasculature. It's really expensive in this instance. The team looking to enhance the flavor, all these sorts of things. But it does have potential, they say, to maybe be used to grow other sorts of meat and potentially even in regenerative medicine. And I said there was a through line to your story, Charmaine. It could be helped to grow meat.

organs, which obviously are in some cases pretty big and require lots of nutrients and oxygen. Now, it has to be said that is a very, very, very long way down the track. And this is the first example. But some folk are saying it's quite a big step that researchers have been looking to overcome. It hadn't occurred to me that the drive for lab-grown meat would also have

you know, a potential side effect of improvements for regenerative medicine. That's quite interesting. Yeah, but of course there are lots of discussions and debates going on around this. Advocates say that lab-grown meat uses less land, has a smaller carbon footprint. Others say it's unsustainably expensive. It's really energy intensive food.

what would be better for the planet and for human health overall would be switching to a vegetarian diet, that sort of thing. But it's an interesting field and one that lots of people are looking at, both academically and in terms of commercial reasons as well. I guess that's it, because I'm someone who doesn't eat meat and I cannot say I find this appealing. And I do on ethical grounds, but the idea that, oh, it's fine because it's grown in a lab, it would be fine because it's grown in a lab, but I don't really...

want to eat it but I guess for a lot of people who are very used to having meat in their diet that would be a great solution is you can switch to something which tastes

hopefully almost exactly the same, but could have a whole load of other benefits if, of course, you can make all of the different numbers add up in terms of energy requirements and how expensive the process is. Yeah, because it's not just about what individuals should be choosing. It's about trying to potentially change behaviour on a larger scale in a way that might, for example, reduce carbon emissions from...

beef production say so I can certainly see something like that having a big impact if it's widespread and yeah cheap enough as you say. Agree but as I say lots of people looking at this and I'm sure this one's going to come up again and again and we'll be here to cover it on the Nature podcast but for the time being let's leave it there for this special edition of the briefing chat and listeners for more on those stories and

and where you can sign up to get stories just like them delivered directly to your inbox. Head over to the show notes. And all that remains to be said is, Lizzie and Sharmini, thank you so much for joining me today. Thank you. Thanks very much. See you next time. Take control of the numbers and supercharge your small business with Xero. That's X-E-R-O.

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Intelligent presence accompanies every mile. Let your Afila One drive or take the wheel yourself. Immerse yourself in cinematic visuals and 360 spatial sound. When you move with Afila One, the journey is a wonderful destination. Afila One. Wonderbound.