Top athlete reveals MND diagnosis, and 2025's Nobel Prizes

0:17Hello, welcome to the Naked Scientist podcast, the programme that brings you the biggest breakthroughs and talks to the major movers and shakers in the worlds of science, technology and medicine. I'm Chris Smith. Coming up is elite level sport linked with motor neurone disease. We examine the evidence as another top level player announces his diagnosis. Also cages that can sieve out molecules, the immune system peacekeepers and the quantum realm. We delve into this year's Nobel Prizes for Science. And how did birds react to the great American eclipse last year?

0:59First this week, motor neurone disease, or MND, is a devastating condition that affects the motor nerves that convey movement instructions to our muscles. It normally affects people over the age of 60, but recently there's been discussion about whether professional contact sports, like rugby, might increase the risk of developing MND. One high-profile case is former England captain Lewis Moody, who told the BBC about his diagnosis just recently, aged 47. A couple of months ago, I noticed I was getting shoulder weakness and went and saw our physio. Kerry did a fantastic job, gave me some rehab stuff to crack on with, and nothing really changed over the course of six to eight weeks, at which point he referred me to a brilliant shoulder specialist.

1:47I had an MRI, neck scan, all that type of stuff. And very quickly when the scans came back, it became clear that it wasn't anything to do with the neck, despite all the years of sort of throwing myself into contact on a rugby pitch. And he then sent me straight to the neurologist, and off the back of the MRI he actually had a phone call with me where I sensed he was preparing me for the worst, which was fairly difficult information at the time. to receive, I suppose. We process lots of emotions over the last couple of weeks. And I suppose when you talk about it, and I generally feel fine when you talk about it, it's never me that I feel sad for.

2:30It's the sort of sadness around having to tell my mum, you know, as an only child, and the implications that has for her. Having to tell the boys, I mean, you know, two brilliant boys, and that was... That was pretty heartbreaking, wasn't it? Lewis Moody isn't the only professional athlete to be diagnosed with the condition. Former rugby players Rob Burrow and Doddy Weir both died of the disease and Gloucester's Ed Slater was forced to retire early from rugby in 2022 following his diagnosis. I've been speaking with Mike Rogers, who's Director of Research and Innovation at the MND Association. Motor neuron disease affects motor neurons.

3:14These are nerve cells that are found in the brain and in the spinal cord, and they tell our muscles what to do by relaying electrical signals to them from our brain. In MND, messages from the motor neurons stop reaching the muscles. The motor neurons die, and those messages don't get through from the brain. This affects movement. It affects speech, swallowing, and breathing. Who tends to get this? Who does it most often affect? That's a really good question. It tends to affect older people more. That's a risk factor. But other risk factors aren't really as well known. It tends to affect more men than women.

3:49But beyond that, it's quite difficult to tell who might get MND. And how will a person who's getting it know that something's up? What do they notice? So this can vary. So onset and symptoms and the progression of the disease can be quite variable in people. Generally speaking, you'll notice things like muscle wastage. You might have a few falls. you might notice some differences in your swallowing and this will be different for different people but it's those sorts of things that people tend to notice and go to their doctor about. And then the natural history what tends to happen once a person's got symptoms they're noticing how does it progress?

4:27MND is a progressive disease it's always fatal the symptoms and the progression can be very very variable in people and how they experience them some people have their movements affected very quickly some people might be able to move for longer but might have their speech affected. So those symptoms and the progression of those symptoms can be very variable in different people. About half of people die within two years of a diagnosis, but then there's a number of people who live quite a lot longer than that afterwards. So it is a very, very variable disease in the way that patients experience it.

4:56If we put sportsmen and women to one side for a moment, what do we think is the main reason people get this? What underlies the disease process? In 85 % of cases, we just don't know. This is what scientists are trying to unpick. We know a lot more about the biology of the disease than we did 10 or 15 years ago. We've seen a huge upsurge in its research, but we still haven't pinpointed that cause in the majority of cases. In about 15 % of cases, there is a well-defined genetic cause and we're starting to develop treatments for those now. And in relation to sportsmen, women, rugby players and so on, what's the evidence that there is an association between people who are doing high performance sports and are developing motor neuron type problems?

5:39So this is still quite uncertain. We don't really know. There's not enough evidence at the moment to really show a firm link. Previous studies have looked into things like does exercise or head impact during contact sport increase your risk of getting MND? And some of these studies have suggested that being an NFL player or being a footballer or being a professional rugby player may increase your risk of having MND. These studies are of interest, but they don't demonstrate a cause or that it's the sport itself that's causing this. Also, MND is rare, relatively rare disease. So numbers in these studies are quite low.

6:14So quite a lot of care is needed in drawing conclusions. Are there any mechanisms that we can invoke to say why individuals who are extremely sporty might be at high risk of this happening to them? There's been a very recent study, which has been led by a group in Sheffield, which has looked at the link between exercise and risk. And this has been a really interesting study. The data suggests that for a very small proportion of men who undertake what they describe as extreme exercise, this extremely high intensity exercise, there's some sort of association with a loss of function in key genes.

6:50And what may be going on here is the protective mechanisms are being switched off, causing this very small subgroup to be more likely to develop MND. What do you think we can do about it? Given that we don't know the cause at the moment, and we just know that there are these possible associations, how should we and how are you pursuing this? And what should be the next steps? We've recently funded a couple of studies. One is a study looking at much larger numbers of footballers. A problem with a number of the studies that have been done so far is that they're relatively small. Can you look at bigger groups?

7:24And looking at those bigger groups will give us more resolution, effectively, in some of these findings. So there's a study going on looking at footballers and their death certificates. That's in England and in Italy. Hundreds, thousands of footballers try and unpick this a little bit. There's also another really interesting study that we funded with a couple of other charities, and that is looking at rugby players and looking at repeat physical trauma and whether or not something that happens in the cells could actually be measured, taking blood samples from professional and academy rugby players to investigate this and to see if they're different compared with blood samples from non-contact athletes.

7:58And what they're trying to do here is identify the pathways that may be contributing to the development of MND. There's also a study that was published last week into traumatic brain injury. Previous studies have been done on this, but again, they've been relatively small and confined to specific groups. This was done by Willie Stewart. It was funded by us and a couple of other charities. He was looking at healthcare records of 340 ,000 people. And what he found was those people with a history of traumatic brain injury, and that can range from anything from concussion, a mild type, to more serious types of traumatic brain injury, and more than twice as likely to receive an MND diagnosis than those who haven't had a traumatic brain injury.

8:38However, what that team also found is that the increased risk was also only confined to the first two years after the injury. And what this suggests is that in some cases, the brain injury might actually be an early sign of MND rather than its cause. So for example, you've got early MND, you might not know, and you would have a fall that causes that injury. so again more research is needed there but that's a really really interesting piece of work into the connection between brain injury and mnd it's an interesting conundrum isn't it but as mike rogers at the mnd association we were listening to there said we do know a lot more about the disease now than we did just a decade ago so let's hope that rapid rate of progress soon bears fruit every october the world spotlight turns to stockholm as the nobel prizes celebrate discoveries that reshape our understanding of life and the universe.

9:27Later on, we will unpack the prizes in physics and in medicine. But first, we're turning to chemistry. With a rundown on who's won what and what for, here's Alice Archer.

9:44The 2025 Nobel Prize in Chemistry has been won for the development of metal organic frameworks by the University of Melbourne's Richard Robson, Kyoto University's Susumu Kitagawa and University of California, Berkeley's Omar Yagi. Metal organic frameworks or MOFs are three dimensional molecular cages composed of metal atoms joined by organic linkers. They enclose cavities which can be used to capture and store other molecules. They can hold large amounts of hydrogen gas for instance and also filter out greenhouse gases like co2 or methane from flu streams they might also be able to work as magic bullets in the body discreetly dispensing sequestered drug molecules into just those diseased tissues that need them mofs owe their existence to the vision of robson who in the 1980s envisioned using metal atoms as nodes and carbon-based organic molecules as struts to link the nodes together.

10:48In a proof of concept, an MOF comprising copper atoms joined by a four-armed organic molecule assembled itself into repeating diamond-like configuration with a generous cavity at the centre of each repeating unit. It was a brilliantly simple yet powerful idea that provided the framework upon which the field would subsequently be built. Robson showed chemists how to think like architects on a molecular scale. Inspired by the concept Kyoto-based Kitagawa went a step further, he created flexible frameworks whose pores could open and close as guest molecules were admitted, demonstrating that MOS could also be smart, responsive materials, and opening the door to the creation of sophisticated molecular machines capable of sensing and sieving substances.

11:39Yagi, meanwhile, had perfected the art of reticular chemistry, stitching molecular building blocks into strong predetermined structures. Applying this to metal organic frameworks, he created MOF5, a crystal that is incredibly light yet has an enormous internal surface area. A single gram has the same surface area as a football pitch. This was the opportunity the field had been waiting for. With this technology, MOFs could operate at scale and potentially solve real-world problems. In the years since, chemists have built tens of thousands of different MOF molecules, combining different metals and organic linkers to produce materials with different architectures and capable of grappling with some of humankind's greatest challenges.

12:26Applications include separating PFAS, forever chemicals, from water, breaking down trace pharmaceuticals and sewage, capturing carbon dioxide and even harvesting water from desert air. For decades, scientists have dreamed of engineering atoms to produce molecular machines with defined functions. Now, thanks to these three chemists, it's really happened. Alice Archer. Stay tuned for physics and medicine Nobels coming up later on. But first, scientists are using the James Webb Space Telescope to gain fresh insights into the atmospheres of distant exoplanets. The research, which has been published in the journal Science, aims not just to learn about that atmosphere though, but to use the information to reveal what these distant worlds are made of too.

13:17Oliver Shortle is from the Institute of Astronomy at the University of Cambridge. We've been presented with this fantastic diversity of worlds beyond our solar system, from Jupiter-sized planets pretty much kissing the face of their star, they're so close to it, all the way out to Earth-sized rocky planets. And in between that lies a sort of zone of mystery, which are these planets that are a bit bigger than Earth, a bit smaller than Neptune, that we have no example of in the solar system. And they've been discovered in most cases by them passing between our line of sight and this distant star and causing a brief dimming of the light from the star as they pass in front of it.

14:02So that tells us they're there and it tells us something about their size. But to then build a more detailed picture, we need to start understanding their composition. and we can get an idea about their composition if we weigh the planet, if we find out how massive it is. And we can do that by looking at the effect the planet has on the star. The planet tugs on the star with its gravity and that causes a wobble in the starlight that gives us a hint about how massive the planet is. And with those two pieces of information we have the first step towards building a more detailed picture of the planet and that gives us its density which critically tells us how much rock there is and how much gas and the more rock the denser.

14:45But what's the next step? Because we've been doing that as you say for a while now we've begun to get some insights into where these things are, how many of them there are, what they might be made of but how can we go a step further now? Yeah so to go further than that is really an area that's been opened up with first Hubble but now the James Webb Space Telescope and what those observatories allow us to do is start looking at that tiny fraction of starlight that passes between the star and our eyes, but through the atmosphere of this distant planet, which allows us to compare the density that we've estimated now with an insight into the gases that are making up the atmosphere.

15:28And that begins now to connect to the interior of the planet. So there is a relationship between what is in the atmosphere and what the planet's made of. Yeah, exactly. And not only what it's made of, but also the climate of the planet. So on Earth, for example, the composition, the chemistry of Earth's atmosphere, both decides the climate, as we're well aware of, with the amount of carbon dioxide in Earth's atmosphere changing how hot the planet is. And when the climate gets changed, it changes how the atmosphere interacts with the interior of the planet. So on Earth, a lot of that interaction is happening through liquid water, dissolving rocks, drawing carbon dioxide out of the air.

16:13On a much hotter planet, if you go to the extreme and get really hot, the planet will melt. And now you've got an ocean of magma at the surface of the planet that's rapidly exchanging gas with the atmosphere and now the atmosphere is directly seeing into the interior of the planet across this atmosphere magma interface. What we're announcing is a framework now for thinking about this diversity of planets that we've discovered all the way from bare rocks that are so brightly illuminated by their host star that all the atmosphere has been blown away out to this other extreme and this is the sort of frontier now these planets that are intermediate in size between earth and neptune where we've got no example in the solar system and we have to work everything out through the light that we can get from these distant stars that's passed through their atmosphere and these are worlds which potentially have vast thick layers of gas and possibly water at their surfaces, asking questions about climates and interiors and possibly also habitability and the ability to host life.

17:22Given we can't go there to actually say, well, has Oliver got it right? How do you know that the inferences you're drawing are the right ones? And that's the really key challenge that we now face. This field is enormously rich because that can't advance just with the astronomical observations alone. That needs to be coupled now with experiments back on Earth in laboratories subjecting materials, water, rock, to the extreme pressures and temperatures that are found in these exotic exoplanets. We can bring all of these disciplines together and ask the question, is the atmosphere we're seeing consistent with these different types of interiors that might be there.

18:07Have you therefore got a kind of a prediction for what a certain body with a certain atmosphere and a certain surface profile would look like so you can then kind of compare what you see with what you think you should see if it fits that model? Or are you observing things and then going that's interesting, how do I explain that or is it a bit of both? Yeah, exactly. So we're both working on fingerprinting from doing the calculations, the models, what these atmospheres should look like for certain interiors, certain climates, certain compositions, and at the same time being challenged by the new data that comes in.

18:45In some cases, doesn't see an atmosphere at all. And we have to understand that. And in other cases, sees an atmosphere, but we're not quite seeing the gases we expect. So we've got to ask ourselves, well, this gas is missing. Is it because it's hidden in the inside of the planet? It dissolves really easily into a liquid water ocean or a magma ocean? Or is it some other aspect of our model is wrong? What sets this apart from just stamp collecting, though, Oliver, going around, roving around the galaxy now, looking at interesting stars that have interesting planets around them and asking this sort of question and then sticking another stamp in your sticker book saying, well, we know what that one's made of.

19:23How does this actually move us forward? What we're doing is we've got this now range of natural laboratories to investigate the fundamental processes that shape planets from their formation through then their teenage years into their middle ages and asking now what needs to happen to leave a planet habitable and inhabited. The key question here is, are these planets a bit bigger than Earth, or are they something completely different? We don't know how big a planet can be before it stops being sort of just an inflated Earth and starts being something completely different, like Uranus or Neptune.

20:01Exciting and intriguing. Oliver Shortall looking at planets light years away and working out what conditions there might be like. The Naked Scientist podcast is produced in association with Spitfire, cost-effective voice, internet and IP engineering services for UK businesses. Find out how Spitfire can empower your company at spitfire.co.uk

20:28Music in the programme is sponsored by Epidemic Sound, perfect music for audio and video productions. This is The Naked Scientist with me, Chris Smith, and still to come, we'll hear how birds reacted to the great American eclipse of 2024. Before that, though, time for the second of our Nobel Prize updates, and this time, the award for medicine. Alice Archer again.

20:57The 2025 Nobel Prize in Physiology or Medicine has been awarded to Mary Brunko of the Seattle Institute for Systems Biology, Fred Ramsdell of Sonoma Biotherapeutics, and Shimon Sakaguchi from Osaka University. Their discoveries have solved a crucial question in immunology. Why does the immune system usually not attack our own tissues? It's down to, they found, a specialized cell type that acts as the immune system's dedicated peacekeeping force. These cells, known as regulatory T-cells, prowl around the body, damping down immune responses to targets that the immune system should ignore. A good example is a developing baby inside a pregnant woman.

21:41It's 50 % genetically unrelated to her. If it were a donated kidney, it would be wiped out in hours, but thanks to regulatory T-cells in the placenta, the immune response is persuaded to look the other way and adopt a state of tolerance. previously immunologists thought that immune tolerance of this type could only be achieved by any self-reactive immune cells being eliminated in the thymus an immune organ active mainly early in life now thanks to these Nobel laureates we know better and our understanding of processes like autoimmune disease allergy cancer and organ transplantation has been revolutionized the story begins with experiments carried out by Sakaguchi in the 1980s.

22:27He had identified immune T cells carrying a specific marker known as CD25. These cells he found had a remarkable function. They actively suppress other immune cells and prevented them from launching self-destructive autoimmune attacks. He named them regulatory T cells or Tregs. The work showed that immune tolerance is an active ongoing mission carried out by these elite cellular guardians. Subsequently, across the Pacific in 2001, Bronco and Ramsdell provided the critical genetic key to understanding these peacekeeper cells in humans. Working together, they linked an autoimmune disease in mice with mutations in a gene called FOXP3.

23:09Mutations in the human equivalent of this gene they also found caused a serious autoimmune disorder. Two years later Sakaguchi linked these discoveries. He proved that the FOXP3 gene encodes a master switch that instructs T cells to become the Treg cells he'd discovered years before and take on their protective role, monitoring other immune cells to ensure that our immune system tolerates our own tissues. The discoveries of these three laureates have unlocked an entirely new branch of immunology called peripheral tolerance. By learning how to manipulate Tregs, scientists are now developing therapies to boost their activity to treat autoimmune diseases like rheumatoid arthritis and multiple sclerosis, or to suppress their activity in tumours, allowing the immune system to attack cancer cells more effectively.

24:01Congratulations to all three on this incredible and richly deserved prize.

24:09Alice Archer and Alice will be back a bit later on to unpack why the quantum world has now been recognised in the prize for physics this year. During the great American eclipse in April 2024, daytime turned to near night for a few minutes and birds, as it turns out, went haywire. Some fell silent, others sang as if dawn had come again, and many launched a false dawn chorus once the sun returned. Scientists decided to plug into this rare natural experiment and also tapped up citizen observations and used machine learning to see how sudden changes in light can upend a bird's daily rhythms. I've been speaking with Dustin Reichard at Ohio Wesleyan University.

24:50We're really interested in how birds would respond to the solar eclipse. And the eclipse was very strange for birds. Humans had the benefit of knowing when it was going to happen, how long it was going to last, and what was going to happen afterwards. Birds had no idea. They had not experienced anything like this at all in their lives. And so it was a normal April afternoon. They were setting up territories, singing for mates, getting ready to breed, and the sun disappears for four minutes. And we wanted to know if they would respond, and if so, how they responded. Did you set up the study in advance because you knew this was going to happen so you thought this is a wonderful natural experiment to do to see how night time coming for a short while when birds are not expecting it is going to affect their behavior?

25:43Yes so we wanted to collect as much data as possible the eclipse began in Mexico and traveled across the central and eastern United States and just in the far eastern tip of Canada. So there was a broad range where we could have collected data, but we couldn't be everywhere at once. And so Liz's idea was to develop a phone app. Anyone with a smartphone, regardless of whether they had watched a bird before, would be able to download this app, open it, and report to us what they observed birds doing during the eclipse. And they could do this multiple times. And this allowed us to gather tens of thousands of data points, right, from all over North America, which was an extraordinarily large data set.

26:27We also wanted to go in and collect some localized data, too. So we set up these passive recording units, which are basically just microphones with batteries attached to them. And we put them all around Bloomington, Indiana, a Midwestern city, where the eclipse was going to last for about four minutes. And so in addition to the data collected by the public, we had these recordings of the days leading up to the eclipse, what happened during, and then the days after the eclipse. So we could see how the birds' vocal behavior, their songs in the calls, changed, if at all, during the eclipse relative to a normal April afternoon.

27:04And did it? It did for most, but not all, birds, which was really interesting. So if we look continent-wide across all the data collected by the public, we saw that after the eclipse, they started to move around more and they vocalized more, almost like this new dawn chorus, right? So if the eclipse was kind of a mini night, when the sun came back, they started to move around and vocalize more. And when we looked at the data from the recordings in Bloomington, we saw very similar things. We had 52 species that we were able to identify on those recordings. 29 of them had a substantial change either before, during, or after the eclipse compared to a normal day.