Diabetes cured with stem cells, and US bans Chinese tech
In this edition of The Naked Scientists: Diabetes fixed with stem cells: scientists reprogramme a patient’s fat cells to produce insulin; also why some security specialists are worried Chinese-made electric cars could pose a threat; and our interview with world-famous stargazer and physicist Brian Cox...
In this episode
01:01 - Diabetes stem cell trial offers hope of cure
Diabetes stem cell trial offers hope of cure
James Shapiro, University of Alberta
A woman with type 1 diabetes has started producing her own insulin three months after receiving a transplant of reprogrammed stem cells. The findings - which have been published in the journal Cell and are based on work done by a team in China - give us hope that type 1 diabetes can be reversed. James Shapiro, a transplant surgeon and researcher at the University of Alberta in Edmonton, Canada, where he’s been working on similar ways to manage diabetes, says the results are “stunning”. We asked him to take a look at the study for us…
James - This group in Tianjin took a patient with type 1 diabetes and they took some stem cells from the fat and they turned those stem cells into insulin producing cells, and they transplanted those cells that make insulin back into the muscle layers in the tummy wall. And after a period of time, it took about three months, the 25-year-old lady was able to come off insulin entirely because the cells were fully functioning.
Chris - How did they persuade fat cells to become insulin producing cells?
James - Well, it's a complex process and they describe it in great detail, of course, in their paper. But they've been testing this idea since 2021, making cells from a patient's fat. And then they basically coax the cells into what are called malleable cells. They've got a fancy name IPS cells or stem cells. And then once they've made these stem cells, they can then wind them forward in time pretending that they're inside the body, inside the pancreas in fact. And by adding different chemical growth factors at different time points, they can coax the cells out into being insulin producing cells.
Chris - Why did they start with fat?
James - Well, I don't know the answer to that. It's a very good question and it's very original. So in our own lab we've been working on blood and there's another group in Shanghai that also did the same thing, taking the stem cells from the blood and then turning them into islet cells. But this group chose fat and it seemed to work very well in their hands.
Chris - How well did it work? So if you look at this lady's diabetic problem, how big of an issue was it for her and how much control did this restore for her? Did did it completely divorce her from the need to have insulin, for example, once they'd done this for her,
James - She had difficult to control diabetes before the procedure. After the procedure, after about three months, she had everything in the green. So a spectacular function of those cells, completely normal at blood glucose, blood sugar profile. Really remarkable.
Chris - How long have they tested her for?
James - She's been followed out for a year, and that's what this report shows. And they've apparently done two other patients who they have not reported on yet. And this sort of follows on the coattails of a different group. This is in Tianjin, just south of Beijing in China. And there's a second group in Shanghai that has done something very similar to this. But they put their cells inside the liver rather than in the muscle layer.
Chris - One of the things leaping out at me about this is if one asks, well why does a person become a type 1 diabetic in the first place? Usually it's because the immune system has wiped out their ability to produce insulin. They develop an autoimmune disease for various reasons. Why doesn't that happen with these new insulin producing cells then?
James - Well, that's a really great question and it might. But this particular patient was an unusual patient because she's had two liver transplant surgeries and she takes powerful anti-rejection drugs to stop the liver from being rejected. And I suspect in this situation, the same drugs that are preventing the liver from being rejected are stopping that autoimmune process. So it has not come back in her to date.
Chris - So in other words, if a person listening to this is type one diabetic and thinks, well this is great, I could just go through this, there may well be a higher price to pay than just turning your fat cells into some new insulin producing cells.
James - I don't know about a higher price to pay. But I think there will be some additional tricks or tweaks that will be needed to stop those cells from being destroyed by the autoimmune process again. And it might be a lot easier to do that than it would be to stop the standard rejection process. The beautiful thing about these cells is because they're the patient's own cells, they're not going to get rejected by the body because of that.
Chris - Can you foresee any other risks of doing this kind of thing?
James - Well, there are potential risks. Because these are stem cell made, it's possible that they could develop into unwanted cells or what we might call off target cells. So they could make cysts or they could make unwanted cell products. This hasn't happened in this case. They've done some very, very detailed and beautiful studies of the muscle layers and shown that they're quite normal, but there is a potential risk. So as this kind of work moves forward, I think we need to be very cautious and make sure that there are no off-target risks to children and adult adults in future that receive these cells.
Chris - But overall, your view is very positive of this.
James - I'm exceedingly excited by this. We've been transplanting islet cells into the liver in 470 patients in Edmonton over the last 25 years, putting cells into the liver. And we've seen some excellent outcomes. But those patients have to take powerful anti rejection drugs to stop the cells from being destroyed by the immune system. If this approach works and if it's safe, this really could be a new frontier for patients with all forms of diabetes. I'm very excited about it.
06:49 - New flu drug fights virus on two fronts
New flu drug fights virus on two fronts
Ed Hutchinson, University of Glasgow
To ‘flu' now, and as the annual influenza vaccine season kicks off in countries like the UK as we head into winter, it’s timely that scientists have potentially stumbled on a new way to fight the flu. They’ve built a small, two-ended molecule that does two jobs: on the one hand it clogs up a key enzyme that flu viruses use to prune themselves free from the cells they infect so they’re able to spread. But once it’s done that, and glued itself to this flu enzyme, the molecule also acts as a homing beacon for the immune system, enabling white blood cells to flock to the site and assassinate infected cells. The findings have been published in the journal PNAS. Ed Hutchinson is a professor of molecular and cellular virology at the University of Glasgow, and he’s been taking a look at it for us…
Ed - This is a really exciting idea showing how in the future we might be able to take a new approach for treating influenza. This combines ideas both from drugs which can target the virus and also from vaccines which can get the immune system to fight back against the virus. This really combines the two. It takes an existing drug which binds to an enzyme called neuraminidase. The virus makes this neuraminidase to chew itself off cells. Its infected so it can get out of them. This drug mimics sugar and it gets into neuraminidase and it gums it up, stops it from working. We've known you can do that for a while. But what we authors realised is that also means that all of the neuraminidase proteins the virus has made, which are all over the infected cell, they're now labelled because they've got the drug stuck into them. So what they've also done is they've stuck something to the back end of that drug, which is recognised by the immune system. So now you haven't just gummed up one of the virus's enzymes and stopped them working. You've also put big come and get me signs all over the infected cell and the immune system comes in, kills the infected cell, takes out the virus. But importantly, it doesn't then cause lots of damage to the surrounding cells and it's immune damage, which tends to make us feel really sick when we're recovering from flu. It's a real surgical strike, which just takes out the infected cell that's there. And using experimentally infected mice, the authors have shown that it's incredibly effective in those mice at resolving really severe influenzas or infections.
Chris - To your knowledge Ed, will it work against or would you anticipate it will work against all the different types of flu? Because flu comes in a number of different flavours, doesn't it? There's animal flus like bird flu. There's human forms of flu and there are multiple forms of the human form of flu. So does this work against all of them?
Ed - That's a really important point, and what's really clever about this approach is that the drug mimics something which the viruses have to target to replicate inside their hosts. And because of that, any virus which grows well in humans should bind to the drug and therefore it should be labelled by this clever strategy and both drugged and attacked by the immune system at the same time, the authors of this paper have done a little bit of work to test that and their initial results in this paper look really promising. I think more work is needed to really show for sure that that's the case, but it really does show, I think, a lot of promise as something which could be really quite broadly protective.
Chris - Obviously this has been done in experimental animals. They used mice. Mice are not people. Would we anticipate that this would work equally well in a person?
Ed - There's lots of differences between mice and humans in general. Obviously if you've met a mouse you'll know that, but particularly when it comes to how they experience diseases like influenza. We start with mice because it is relatively easy to do experimental work on them. But things which are promising in mice do then need to be tested in other animals and ultimately in humans. And lots of things along the way we find unexpected reasons why they don't work as well as we'd hoped. So this isn't an absolute knockout and it's definitely going to get into humans tomorrow. All things being equal there's probably another five, ten years of work that's gonna be necessary to really test that unless there's some major crisis which forces people to develop influenza drugs quickly. But this is a really promising start for something which could be then taken further.
Chris - And could that major crisis be bird flu? Because we've been watching this very closely for the last couple of years and it's gone from lots of birds affected to now interesting things happening with cows and an ostensibly bird virus spreading through udders and milk in cows into calves. So it's sort of one step closer to us. Could this be a provoking factor to accelerate these trials?
Ed - To be very clear, we're not yet in a situation where H5N1 is spreading in humans, but it is something which we are looking at with a lot of concern. And if we think back to the last time there was a pandemic during SARS-CoV-2, people did start to develop drugs a lot more quickly than normal then because there was a massive need. However, there is an important difference between influenza and SARS-CoV-2, which is that influenza has been around for ages and actually in recent years there've been multiple new classes of influenza drug developed. So we already have quite a good arsenal of influenza drugs ready to go. If a crisis arose, a new one would certainly be valuable. And I think this could be a really useful addition to that. But it's not like the situation with SARS-CoV-2 where we were really starting from a cold start and needed to develop drugs when we had none at all to begin with.
12:45 - US bans Chinese and Russian tech in cars
US bans Chinese and Russian tech in cars
Ciaran Martin, University of Oxford
The United States has said it is banning certain technology made in China and Russia from cars, trucks and buses. US officials claim the technology in question poses a security risk to vehicles that operate within its borders. So, what should we know about it? Here’s the University of Oxford’s Ciaran Martin. Ciaran helped set up the UK’s National Cyber Security Centre…
Ciaran - I think it is a worry in two different ways. One is that these things need to be secure. So these things in effect, the software in particular will issue commands, they'll respond to instructions, so they'll tell the car what to do or they'll beacon out a request, essentially, to connect to something to help the car move. And its software can be full of flaws. That means it can make mistakes, but also it can be hacked into. So you can see where at least the theoretical worry is that if you don't design this properly, and then even if you design it properly if you don't secure it properly, you could interfere with the car. The second worry then is about data. Clearly in a very contested world with great power rivalries and the US, for example, seeing China and Russia as threats, where people are, where they're going, their pattern of life, what they do is of great interest potentially, at least in respect of some people. And if their cars are also, as well as computers on wheels, just automatic data generators on wheels, you can see the spying risk. And taken together, I think the American government has said that part of its, if you like, risk reduction strategy is to ban component parts for the hardware and software for modern vehicles coming from China and Russia after the implementation period.
Chris - Are we at risk of throwing out the baby with the bath water though? Because for instance, as one engineer told us who works on roads earlier this year, there is enormous amounts of very helpful data being collected by drivers all over the country all the time, which is now helping them to tell the national highways where the potholes are. That's just one example, but we've got a wealth of data flowing in that can make driving safer, can make road usage more convenient and safer. And if we're not careful, we could end up losing that.
Ciaran - The issue here isn't really the collection of data. That data will still be being generated. It's the security of the data that is concerning the Biden administration. So it will presumably plan to use the data itself for the very things you've talked about in terms of road improvements. It wants to make sure that sensitive data, for example in sensitive persons or around sensitive areas, isn't easily available to those they might see as adversaries. I think the challenge is slightly different. It's not so much throwing out the data baby with the bath water. It's actually about the holistic way in which you need to secure these things. Just because something's made in China or Russia and frankly we're talking China here, Russia doesn't make that much of this stuff. So what the Biden administration has announced is essentially about China is a perfectly defensible part of the risk reduction strategy. But if something is made in China, it's easier for China to manipulate it or to steal the data from it. But even if it's not made in China, if it's not properly secured, it can be hacked into by China or somebody else. So I think this is only one part of a strategy and to be honest, for me it's not the most important part. The most important part is securing these things properly.
Chris - Do you think or do we have evidence that they're already compromised a lot of these and other devices and so that this is prudent politics, they're acting on this on good information?
Ciaran - I think it's a defensible and sensible measure, but I think it's not the total answer to securing modern vehicles. In fact, I don't think it's close to the totality of the necessary answer. I also think it's important we shouldn't panic people here. We shouldn't allow, and we're not allowing, modern cars to be built in an absolutely crazy way where a glitch in software drives you off the road or stops your brakes from working. Where an easy to do computer hacking operation does the same things. We're not allowing cars to be built in that way and it's actually going to be fiendishly difficult, assuming we do this properly as I believe we are doing, it's going to be fiendishly difficult for even the best hacker to target a particular car to know that that particular component with a particular software vulnerability is in a particular car at a particular time and do something really, really malicious to it. So let's not overdo the risk. As long as we're sensible about the way we build these things and the way we regulate the safety of the product, we shouldn't be talking about sort of human catastrophe situations. I think the data risk is more of a worry. It's harder to secure, but again, just banning particular countries doesn't completely negate that risk.
Chris - I'm slightly surprised we're talking about cars. Not you and me. I mean as in politically in the world. Because haven't we had all the same conversations already with 5G and the UK infrastructure and also people worried about nuclear power plants that are being constructed by China or by Chinese organisations in various places?
Ciaran - I think each case is slightly and subtly different. There's one similarity with the 5G discussion that I know very well, which is that restricting or banning a particular country doesn't automatically completely secure a 5G network. If our telecoms infrastructure has historically been quite insecure. And I think the British government's reforms of a 2022 change in the law were vitally important in saying not just that Chinese companies couldn't do this or that, but also saying anybody building telecoms infrastructure had to conform to much higher security standards. For example, Russia, which is a voracious hacker of critical systems, but doesn't have any telecoms equipment of its own, so that Russia can't easily hack into these systems. So that's one thing they have in common. Where I think it's slightly different is you could take a completely hawkish approach to Chinese trade and say you're not going to buy clothes from China, but people don't see a strategic risk from clothes. What about a piece of metal? What about a battery that doesn't do much? Then you get into components and some of the components in cars will do very little. Some of the components in cars will do quite a lot. And you want more restrictions on the latter, but also you'll wanna make sure that the components that are quite clever and that can effectively control the car are safe from all sorts of external threats, not just they're not built in China. So there are different things that apply to different situations. You mentioned nuclear power that was essentially about who financed it, not so much who built it. With 5G, it was about who built some of the hard infrastructure for the big bits of mast and so forth, that power telecoms networks. What we're talking about here is the little bits that drive modern cars.
19:43 - Brian Cox's 'Solar System'
Brian Cox's 'Solar System'
Brian Cox
Professor Brian Cox has got a new TV show coming out. It’s called ‘Solar System’, and James Tytko went to meet him at BBC Broadcasting House to find out why, in his view, it’s the right time to revisit our cosmic back garden...
Brian - It felt like it was time to make a series really focused on the data that's coming in. Now, for example, in this series, you'll see data from Juno around Jupiter of eruptions on Io. That's data from this year, 2024. So we see Io is the most volcanically active object in the solar system. And the reason is because of what's called the orbital resonance, so the way that the other Galilean satellites interact with Io, which means that it is in an elliptical orbit around Jupiter, which means there are tidal forces on it, which heats it up. And so I like the sense that this is a snapshot of what's happening now and what we are observing now in the solar system.
James - Why are volcanoes so interesting to people studying the solar system? What are the big clues they provide to the big questions we want to answer?
Brian - So if we start on Earth, they're a central and essential part of our geology. And as I say right at the start of the first episode, you might say, well, why are we interested in geology? I mean, it's an interesting science in its own right, but one of the reasons we are very interested in it, if you think about what the origin of life must be, it has to be a transition from geochemistry to biochemistry. Because of course you start with a load of things, the solar system, in this case that formed four and a half billion years ago and there was no life. And then you get geologically active worlds and it's in what we might call out of equilibrium conditions, chemical and thermodynamic, that complex carbon chemistry emerges. So volcanoes and associated with the volcanoes actually on earth plate tectonics are central to the Earth's climate and also to those chemical processes that would've led to the origin of life here in this case around 4 billion years ago on Earth.
James - That's actually an interesting question that I think bears some description, which is where the Earth's heat comes from in the centre of it in the core to drive the volcanic activity that we see on it.
Brian - So about half, at the moment, about half the energy that's there in the Earth core is essentially from the formation. So it's like dropping a rock, basically. You drop a rock to the ground and it gives up its gravitational potential energy, and it's a thing we all do at school. And you hear a bang and it hits the ground and it heats the ground when it hits it. And so part of the earth's store of energy is coming from that, the formation four and a half billion years ago, which is gravity ultimately. And the other half is from radioactive decay of nuclei. Uranium, and radioactive elements like that in the core. And so when you look out into the solar system, one of the first questions you would ask is, well, are there other places which have similar geological activity? So you see it on the surface of Mars. So it's obvious, you just look at Mars, you see things like Olympus Mons, the biggest volcano in the solar system. But those volcanoes are extinct. It's smaller than Earth, so it lost its heat more quickly. And so it's essentially an inactive world ish. So, the point about Io is that it's interesting because it's a very small world where the origin of the energy, so the origin of ultimately the energy that dries the volcanoes is coming from the orbits. And so we did do it, I hope we did it justice. What we ended up filming was the way that I explained it to the director <laugh>, the way that I found of explaining it, because it's quite interesting. It's about the way that Io is tidally locked and the face of Io is locked to the empty focus of the ellipse and not to Jupiter, but the tides are raised obviously on a line going to the planet and so on. So it's quite a complicated story actually.
James - I wonder if we could fill in a little bit of the picture as to why geothermal energy and volcanic activity might be the place to look when we are thinking about origins of life on Earth. And then why are we looking at that further afield in the solar system?
Brian - If you think about chemistry getting complicated, by which I mean very complicated, which is it becomes biology. What we know is that to drive chemical reactions like that, you need differences in temperature, differences in chemical composition and so on. Where does that come from on a planet? Ultimately those conditions are geological conditions. One of the weird things about life on Earth, you have to imagine these imbalances in protons, across membranes in the cells. And that's one of the things, one of the chemical properties, that all life shares and exploits. And it's a bit odd really, because we tend to think of life as being electrons moving around, right? So photosynthesis, we learn about that. It's all about the electrons moving, but actually underpinning that is this proton stage and it's chemistry that's shared by all living things on Earth. So as you infer, therefore it must have been something to do with the origin of life, at least the population of things to which we are all related, which is often called Luca, the last universal common ancestor, it must have had that property. But there's a hint of geology about it, geochemistry. So you have a candidate then for the cradle of life on Earth based on observations of the properties, the chemical properties of life today and geochemistry that exist today on Earth. And so we go to look for those places. If you want to look for life beyond Earth in the solar system, it makes sense to look for places where those conditions are present and those conditions are present. We think on Europa, Jupiter's Moon, Europa, we're not entirely sure. So that's why we've got a couple of missions on the way now. And also Saturn's moon, Enceladus. Is another one. But again, we are not entirely sure. So we need a mission there. That's one of the ways that we steer solar system exploration in terms of the hunt for biology, is to look for those conditions.
Do snails get dizzy?
Thanks to Jon Ablett for the answer!
James - The first thing to say is that we humans feel dizziness as a result of our vestibular system. That is the sensory system in our inner ear that helps us maintain balance and spatial orientation. If you spin around really fast fluid in your ear moves really fast too. This will start to make you feel dizzy even while you're still spinning. But when you stop, the liquid in your balance organ keeps moving for some time after. So your brain gives you the disorienting feeling that you're still spinning. But what's going on in snails? Do they have similar anatomy to us in this regard? John Ablett is senior curator of moca at the Natural History Museum.
Jon - How do snails understand their 3D position in their environment? They do that through statocysts, and these are structures in the head that sense movement and orientation in relation to gravity, and of course acceleration and deceleration. And it's similar to how a fish senses its position in an aquatic environment. So statocysts are capsules filled with liquid and there are statolith lifts floating within these. And as soon as the snail moves or changes its position, inertia makes the statoliths float, hitting the statocyst wall. And there are small hairs that detect the contact point, which is then processed and allows the snail to work out its position in space. So that's how a snail senses its environment. And this is very different from how we do. And so in short, although it's probably very hard to say for certain, it's very, very unlikely that snails get dizzy.
James - Unlike our more sophisticated vestibular system, complete with semicircular canals, which indicate rotational movement, snails rely on less information-rich signals detected by hairs surrounding status assist as they knock into them, which is why we think snails probably don't get dizzy.
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