Weight loss jabs, COP29, and Brainy birds

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BBC Sounds Intro

1:09BBC Sounds. Music, radio, podcasts. Hello, welcome to this week's 5 Live Science. I'm Chris Smith from The Naked Scientist. Coming up, what's at stake at this year's UN Climate Summit? Also, the 80 million year old fossil revealing how birds came by their big brains and why the UK's oldest satellite has wandered off over the Americas. Plus, a little bit later on... If your diet was so rubbish to begin with, right, and so therefore you had to eat quite

1:39a lot of it to make sure you had enough micronutrients and protein and what have you, suddenly you take these drugs and these drugs are so effective at making you feel full, you just eat less. You could actually, depending on how rubbish your diet was to begin with, tilt into malnutrition. Can weight loss jabs solve the obesity crisis?

UN Climate Summit

1:59The Naked Scientists on 5 Live. First this week, leaders from almost 200 nations are attending the UN Climate Summit in Azerbaijan, amid warning next year could be the hottest on record. The politicians are hoping to agree a financial plan to help lure both poorer nations and oil and gas-rich states away from their reliance on fossil fuels. Mark Maslin is a professor of Earth System Science at University College London. He'll be attending the COP Climate Summit, and I began by asking him why,

2:32wealthier nations, like the UK, were taking the lead at this year's gathering. If you have a look at the top 10 emitting countries, a lot of them are the industrial countries right from the beginning. The USA, all the European industrial nations, and the UK. And it's interesting, if you add in land use changes, you get other countries that are in that top 10, including Indonesia and Brazil, because of the huge changes.

3:02So we are one of the top 10 historic emitters, and therefore we have that legacy. And no, we've done incredibly well. Remember, we've gone from 2% of our electricity generation coming from renewables in year 2000, where now up to 50% of our electricity comes from renewables. So the UK's done really well cleaning up its act, but we have that historic legacy that we have to acknowledge and also help other countries to go on the same journey that we're

3:34going on. It hasn't escaped the attention of many around the world that COP29 is being hosted by Azerbaijan, which derives enormous amounts of its revenue from the oil and gas industry, and people have questioned their commitment. What's that looking like? So I think this is a misunderstanding of international negotiations. The reason why all 196 countries need to get together to talk about these issues is because how do we help a country like Azerbaijan, who 90% of its export money comes from oil and gas?

4:11So if we want this country to move away from fossil fuels, how do we help them build a different economy, which is just as profitable, that allows them to actually develop their economy and help their people out of poverty? We need to do this as an international community, because if we just stop oil and gas from Azerbaijan, then it will then plunge that country into abject poverty. So we have to think of this as a system-wide issue and not just blame countries, because

4:42they have a natural resource. There is a huge global demand, because remember, 80% of the world's energy still is produced by fossil fuels. So they're still really important. But how do we actually help them transition? They also have a record, though, in government terms of leaning on people who say, do, and criticise in the wrong sort of way. So the issue we have is that we are dealing with an international community where governments vary hugely from full democracies to full dictatorship.

5:19And therefore, this is why something like the COP is really important, because we need to actually take all of the countries of the world on this journey. And part of it is about negotiation. Part of it is by signposting. COP in Paris actually agreed in 2015 that we were going to limit CO2 emissions to two degrees warming or an aspirational target of 1.5. And that means going net zero. So this obsession with net zero comes from the COP meetings, and therefore it's permeated

5:54every part of our culture and economy. But we need to then work out how we actually activate that. How do we actually move all of the countries, whether they are a totalitarian state or whether they're a full democracy? And that's why international negotiations are incredibly difficult, very tricky, but absolutely essential. Mark Maslin from UCL there.

Mosquito-Borne Diseases

6:18Now, there's been some promising news in the fight against mosquito-borne diseases like dengue, Zika and yellow fever. A study at the University of Exeter has found that one particular bacterium, which lives in the insect's intestine, can fuel the growth of mosquito larvae, so they can mature much faster and may even turn into bigger adults. Now, why on earth would you want to make more and fatter mosquitoes? I hear you scream. Well, it could have implications for improving the breeding programmes that are used to rear

6:49modified mosquitoes that have been designed to control wild mosquito populations and therefore disease spread. Here's Ben Raymond from the University of Exeter. The problem I wanted to address was really how to grow more and better mosquitoes for use in sort of biological control studies of mosquitoes. I'm glad you added that last bit, because when you first said, I'm trying to find out how to grow more mosquitoes, immediately I thought, well, most of the world is trying to get rid of the blinking things. There are thousands of species of them and they are the most dangerous animal on earth.

7:22Yes. As I tell my students in many introductory lectures, there's a higher mortality from mosquitoes than any other animal on the planet. For the context, it's important to realise that releasing mosquitoes in various ways is now an increasingly important part of how we control mosquito-borne diseases. And there's a whole range of technologies that do that, ranging from classic sterile insect release, so that's just releasing lots and lots of sterilised males, which swamp the

7:53native population, males that carry particular microbes, this one in particular, Wolbachia, that induces sterility in the females, but can also prevent those female mosquitoes from transmitting viruses. So there's a whole raft of technologies involved in releasing the particular strains to control mosquito populations. But it all centres critically on being able to produce enormous numbers of mosquitoes, and that is the issue that you're kind of going for. Yes. So, for example, there's a recent trial in Singapore.

8:24They released 100 million mosquitoes just for an experimental study. Another study releasing these Wolbachia to prevent transmission. They would release 100,000 mosquitoes per kilometre squared per week for 16 weeks. So really very, very large numbers. What can you do then in order to make that a more efficient and rapid production process to breed up those mosquitoes that you want to release? The starting point for this study was we went into this particular mosquito, the yellow fever

8:59mosquito, and it's been known for a number of years that this has to be colonised by bacteria. It has to have what we call a microbiome in order to complete its development. Without being colonised by microbes, the larva will not develop and will not form a pupa and can't produce adults. So we know it needs to have bacteria, and it did raise the question as to, you know, we can actually control what bacteria are colonising the mosquitoes and try and find ones that either can accelerate development or make bigger or better mosquitoes.

9:32So that's the kind of the starting point. What have you actually done in that direction? So we wanted to look at this little odd little microbe, Aesia, which is found in nectar, and we know from studies in other mosquitoes that it has strong association with mosquitoes that transmit malaria, the genus anopheles. So we wanted to look particularly in this yellow fever mosquito to see if they also could form an association with mosquitoes and would have any impact on their development. How? For these mosquitoes, it's quite easy to make sterile insects.

10:04You just need to sort of surface sterilise the eggs, and then we can rear them in sterile water. We can then add in our bacteria of choice. And what sort of a difference do they make when these ones you've found are there? How different is the maturation process for the mosquitoes? So yeah, so it only takes about nine days to make an adult from egg to pupa, so quite rapid development, so we could shave nearly a day off by adding one of the species of Aesia that

10:35we put into the rearing water. And in particular, we showed that when we added Aesia to the sterile animals, we didn't get much of an improvement. We got a little bit of improvement, but actually we could find nice, robust effects on the sort of normal reared mosquitoes, which is kind of important if you want to take this into an application. So in other words, they're better when they're part of a community, a mixed community of microbes. They add something. Do you know how they're doing this? What are the bacteria in the mosquito gut doing to speed up growth in that way?

11:06The bacteria in the gut have to make an environment that's starved of oxygen, so they have to remove the oxygen from the gut, and that lack of oxygen drives the hormonal changes which signal molting for the larvas. So that's one thing we know the bacteria are actually required for. We don't know if there is any sort of nutritional role these bacteria play. What the Aesia do is they don't seem to persist very long in the larvae. It's quite a curious result. But what they do do is have a long-term effect on the makeup of that bacterial community for

11:41the duration of the larval stage. How would you use this then? If you can shave off a day, that's 10% off of the rearing cycle. Does that mean that you could knock out lab-grown mosquitoes about 10% faster and in possibly therefore 10% greater quantities? That was one possible implication. The other thing we've looked at is we can also, in some cases, make the mosquitoes slightly bigger as well. So we're not only making them faster, but in some cases we can make them larger males

12:12and sometimes slightly larger females and get that boost in development rate. So hopefully more than one benefit. Ben Raymond there from the University of Exeter.

UK's Oldest Satellite

12:24This is 5 Live Science with me, Chris Smith. Still to come, how the UK's oldest satellite has ended up somewhere completely unexpected, but why did someone move it, and whether weight loss injections can help to tackle the global obesity crisis. But first, researchers at the University of Cambridge have described an extraordinary fossil of an ancient bird. The 80 million-year-old specimen of an early bird species called Naviornis is so well preserved and comes from a period that's so poorly understood in the evolutionary history of these animals

12:56that zoologists think it might revolutionise our understanding of how modern birds came by their surprisingly big brains. The findings have been published in the journal Nature, and I went to meet Guillermo Navalon-Fernandez to find out more. Birds, modern birds, have very large brains and very complex brains, and we actually don't know where and when these evolved, which is one of the biggest mysteries in vertebrate evolution. Birds are direct descendants of dinosaurs, aren't they?

13:28So does that mean dinosaurs potentially were brainy? They were certainly the ancestors of birds, so if birds are brainy, perhaps they were too. This is what we thought for a really long time, and definitely dinosaurs had more complex brains than other groups of reptiles. However, we know that they are still very far away from the condition that we see in modern birds. So even the first birds that we have three-dimensional brains from, that we can see the form of this

14:00structure, like Archaeopteryx, the earliest bird that lived around 150 million years ago. These early birds have these brains that are still very similar to dinosaurs. So there's a gap there. We've got very early birds, very similar to dinosaurs. Their descendants, modern birds, big brains, quite different, and we want to know what sits in that gap over, what, about 60 to 100 million years? Yeah, so we are talking about a gap between 70 and 60 million years, because we have Archaeopteryx,

14:33150 million years, and we know that the modern birds appeared at the end of this Mesozoic era, or the age of dinosaurs, at around 80 million years ago. Now, we know a lot about the birds that came evolutionarily in between these two endpoints in evolution, but the fossils that we have from these birds come from fossils that are completely flattened. So this has opaqued our ability to reconstruct the three-dimensional morphology of what's

15:08happening within their skulls, which also includes the shape of the brain. What have you got, then, in your hands now that helps to address this problem? We have been working since 2021 in this spectacular locality in the south of Brazil, and we found these very unique birds preserved in three dimensions. So that allowed us to reconstruct or have a very good representation of how the skull of

15:40these animals that have the brain inside were like. So we could reconstruct the morphology of the brain of a bird that is right in the middle in the evolutionary journey between Archaeopteryx and modern birds. What's the timeline, then? When do these fossils date from? We currently believe that these fossils date from between 80 and 70 million years ago. We are talking about the end of the era, the age of dinosaurs.

16:11How big would the bird in life have been? How big was its brain? We are talking about starling-sized animal, and the brain was more or less 10 millimeters end-to-end, which in a starling, it would have been bigger than that. So we are talking about a brain that is relatively smaller relative to what we are used in modern birds. It really is, then, that stepping stone. It's bigger than Archaeopteryx, but smaller than a modern bird brain.

16:41So it is arguing that brains were beginning to get bigger in these birds as they began to evolve towards the tail end of the reign of the dinosaurs. Exactly. This is precisely what we believe at the moment. This new brain is showing us that the size of the brain is increasing in these groups, but also it's telling us the sequence of evolutionary changes that led to the origination of the modern brain. And by that, I mean it's telling us the sequence of expansion of the different areas of the brain, because it was not a constant sort of expansion of the total brain.

17:15Some parts of the brain were actually expanding to modern standards, while other regions of the brain were not expanding at the same pace. Which bits were getting bigger? And in biology, when things change in that way, they usually change for a reason. So what was driving this change? So we are still unsure about the specific drivers. Some of the characteristics of this brain that are quite modern is, for instance, the general

17:47architecture of the total brain. And by that, I mean that the brain is starting to fold, to flex upon itself, kind of like what happens in humans. However, we see that many of the other regions of the brain, for instance, the cerebellum, is still very flat and very small. And we know that this area of the brain is very important in modern birds to coordinate very complex mechanics of flight. So we have no idea how Navaornis and the rest of the group that Navaornis belongs to were

18:23flying effectively without this neuromotor coordination, this very complex neuromotor coordination, because we know from many other aspects of the anatomy that they must have been flying very well. As any scientific finding solves some questions, we are also left with millions of new questions that we have absolutely no idea what they mean. So still some work to do, but fascinating nonetheless. That was Guillermo Navaorn-Fernández, and he's at the University of Cambridge.

18:55The UK's oldest satellite was launched into space in 1969 to help with the communications of the British Armed Forces. Years later, Skynet 1A, as it was known, was decommissioned, and space scientists predicted that gravity would gently pull it towards the Indian Ocean. But instead, it appears to have mysteriously been redirected, so it now occupies airspace over the Americas. But no one seems to know why. The space consultant Stuart Eves has been investigating the puzzling progress of Skynet 1A, and he brought

19:30me up to speed with what he's found. When I started researching this, I rapidly convinced myself that there was no realistic prospect that sort of natural perturbations due to solar radiation pressure, the push that the radiation coming off the sun gives the satellite, would ever be strong enough to overcome the gravitational forces which would leave it oscillating around the Indian Ocean. So I concluded that it must have been deliberately moved by firing the thrusters on the satellite

20:03itself, but by whom and when wasn't at all clear. When did someone notice it was in the wrong place then, Stuart? I think that was probably me. We are required as a nation to inform the United Nations of the locations of all the stuff that we have put into space. And because it's our oldest satellite, the first entry in that registry is Skynet 1A. Its location on the geostationary ring says 105 west.

20:34And I looked at that and thought, well, surely that's not right. I was pretty confident that the satellite had operated somewhere near 40 degrees east when it was operational. And as you'll readily appreciate, you can't even see 105 degrees west from the UK because it's too far around the planet. So it initially looked as if there was some sort of mistagging or error in the catalogue. But over the time of my investigation, I've become more and more convinced that the thing

21:06that is at 105 west really is our satellite. And that's why it's puzzling as to how it got where it is. So how do you think it did get there? So as a result of some of the publicity that this story has generated recently, I have found some additional information which seemed to confirm that the satellite was actually manoeuvred in 1977. So that's considerably after the information that I'd been able to find.

21:37I found reports that were created by what's known as the Royal Aircraft Establishment of Farnborough at the time. And they went up to the end of 1973. And then the trail went very, very cold. And I think that's probably around the time when the satellite stopped providing a useful function, i.e. the actual communications payload probably wasn't working. I think the satellite was still capable of receiving commands to do things like make manoeuvres.

22:08And as far as I can tell, in 1977, a decision was taken to actually move the satellite across the Atlantic. And I'm fairly confident that both the UK and the US must have been involved in the decision to actually do that. So someone would have known, probably multiple authorities would have known, but they just kept quiet and they didn't update the official register. That's what you're contending. Why on earth would someone want to do that with the defunct satellite? It argues there was some other reason for wanting to park it back over the Americas.

22:42So it's possible that the satellite was transmitting on a frequency that was causing some form of interference and that they wanted the frequency clear for, you know, other satellites to use. So they decided to kind of move it out of the way to avoid the radio frequency interference. The other hypothesis that I have is that you have to remember that we're in the very early days of geostationary satellites. Technology is not well developed specifically.

23:12A lot of the subsystems on the satellite would have been flying in space for the first time. And it's possible that although the UK didn't have much utility for the satellite because it wasn't providing a useful communications function anymore, it's possible that its builders over in the United States might have thought, well, it would be quite interesting to see how the different bits of the satellite, you know, the batteries and various other subsystems are standing up to the radiation environment in space. So they might have been quite keen to sort of have it back and be able to watch how it degraded over time

23:47and how long it lasted. And I was hoping you were going to go up with something a bit more X-Files than that. So it is quite interesting. The sort of advertised function of the satellite was definitely about military communications for UK forces. But there are bits of documentary evidence in various books and things that I've been able to find that suggest that GCHQ was also making use of the satellite. Today, if you launch a geostationary satellite, you were assigned a particular location, essentially

24:19assigned a particular longitude. And it's your job as satellite operators to sit your satellite at that longitude and not move around too much because potentially you'll cause interference if you drift backwards and forwards. But there was very little else in geostationary orbit when Skynet 1A was operational. And it was allowed to drift backwards and forwards by up to about 20 degrees at times. That aspect of it would have been quite consistent with GCHQ using the satellite to try and work

24:53out where various foreign transmitters were, for example. So I did get my X-Files moment eventually. That was Stuart Eves.

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Global Obesity Crisis

25:32This week, we are exploring the extent of the global obesity crisis and whether fat jabs might be the answer. The Naked Scientists on 5 Live. They've been heralded as a magic bullet when it comes to tackling the global obesity crisis. And these new agents have also been incredibly lucrative for the people who make them. Nevertheless, health caveats have emerged and they're not without significant side effects for some. We'll hear about those and explore the role that these new drugs can play in tackling

26:05obesity shortly. But first, what exactly is the scale of the problem that confronts us? Here's the Cambridge-based biologist, Giles Yeo, who's author of Why Calories Don't Count. We began by discussing exactly what obesity really means. It's simple in some ways. So clinicians would typically define it as a body mass index, and that is your weight in kilograms divided by your height in meters squared. So BMI above 30 is considered being obese or clinically obese.

26:37The problem with that, obviously, is that it literally is just a number on a scale because it doesn't take into account anything else about how much muscle you're carrying, you know, or your ethnicity. So I think a better definition of obesity and what people are now, you know, iterating towards is carrying too much fat that it begins to influence your health. And if one looks at a population like the UK, what fraction would fit the criteria based on the traditional way of judging obesity, that BMI measure greater than 30?

27:11And what fraction fit your criteria of saying, well, it's a pathological accumulation of fat that's affecting your health? I don't think the numbers are all that different. They just include slightly different people. So the numbers within this country sit between one in four and one in three. In the United States is one in three. Here is between one in four and one in three, 25 to 33% have obesity based on pure BMI. But if you then begin to think, so East Asian people, people that look like me, Chinese people, South Asian people, so Indians, Bangladeshis, Pakistanis, we famously can't get that large

27:47before we get into risk of disease. So if you now take away white people, okay, Polynesians type type of people who can get to quite large before they get into some risk of disease. And then you include small frame Chinese people and smaller South Asians and stuff. I think the numbers probably still bear out the same where about one in four people will have obesity. And in what way is it influencing their health? If we follow people up who are in those criteria for being considered overweight or obese, what

28:19does that do to health? So broadly speaking, we're talking about metabolic disease. And I guess the question is why that actually happens. And so people have a misconception of what happens when you gain weight and lose weight. They think that you gain fat cells and lose fat cells. And this is just not true. So your fat cells are like balloons. They get bigger when you fill them up and they get smaller when you lose weight. And the safest place to store fat is in fat because they're your professional fat storage organ, right? The danger happens is when your fat cells become full.

28:50And when they become full, the fat then has to go somewhere else. And it goes to your liver. It goes to your muscles. It goes to your pancreas. It goes to your kidneys. It goes to tissues and organs, which are not designed to store fat at high levels. When these tissues begin to get full of fat droplets, your liver becomes like foie gras, for example, it begins to influence the function of that organ. And when that happens, you then tilt into metabolic disease. And this includes stuff like type 2 diabetes.

29:20It could include fatty liver. It could include high cholesterol levels. It could include high blood pressure. And each of us has differing amounts of fat we can store safely. We each have different safe fat storage capacities. And when a person puts themselves on a diet, does that actually reverse that state? Or do you lose the fat from the adipose tissue where you would normally store fat first and leave behind the bad fat stored where it shouldn't be? Or is it the other way around? Now it depends on how long you have been fat for.

29:52Okay, so your liver, for example, getting filling with fat and then disappearing, it's actually a relatively normal thing to happen. So in other words, if you had a big, gigantic meal and you ate lots of rich food, you will get some fat in your liver because that's almost its natural state of affairs. So when you lose weight or when you stop eating, then the fat disappears away from your liver and it tends to disappear away from your muscles as well. Now, if you then end up with a situation, however, where you've been fat for so long or you've had obesity for so long and it begins to damage the tissue, such as damaging your liver and

30:26what have you, well, then you end up with longer term disease even once you've lost the weight. So really, it depends how long you've been carrying that extra fat for. We're therefore brewing up two problems, aren't we? We're brewing up an obesity crisis because lots of young people are getting fat, but we've then got health problems caused by long-term overweight. Yeah, that's true because actually it is seldom obesity itself per se that is the problem. I mean, there are issues with being too large. There are issues of gravity, arthritis, you know, sleep apnea.

30:58So that's the inability to breathe properly at night because of the sheer amount of fat that's on your chest, for example, you know, and immobility. But what actually kills you are these associated metabolic diseases, okay, type 2 diabetes, high blood pressure. And the issue is, particularly if you get obesity young, and we are seeing increasing numbers of young children with obesity, then you spend longer in life, okay, with these diseases. If you're now getting the disease as children, you now have to spend 70 years of your life,

31:29you know, suffering from those conditions. So it's a problem in terms of many, many stages. But do we actually have the data, Giles, to say, well, if I am continuing to live the lifestyle I was living that got me overweight in the first place, but I take these injections or these drugs and they cause me to lose some weight, but my lifestyle remains the same, does my disease risk actually change with that? Or do I maintain the original disease risk because my lifestyle that is bad for me has

32:01continued? I'm just getting away with it. That's an excellent question. So I think just by losing the weight, just by reducing the amount of fat, which is what these drugs will do, you will have a health effect. And so that is going to have a health benefit. But you're absolutely right. If your diet was not so great to begin with and you ate lots of chips and cookies and Oreos or whatever it is you were eating, then all you're going to do is eat less of those items. They're not going to actually improve your diet. In fact, if your diet was so rubbish to begin with, right, and so therefore you had to eat

32:32quite a lot of it to make sure you had enough micronutrients and protein and what have you, suddenly you take these drugs and these drugs are so effective at making you feel full, you just eat less. You could actually, depending on how rubbish your diet was to begin with, tilt into malnutrition. So these drugs should not be used in isolation. They shouldn't just be given out. They should be prescribed and they should come with a suite of wraparound treatment, shall we say. All right. And this includes some form of dietary advice or intervention or something that's out there

33:06and probably actually some form of exercise regime as well to prevent you from losing too much muscle mass. So you're absolutely right. The drugs do one thing and one thing only. They make you feel fuller and so you eat less. You still have to improve your diet. You still have to improve your lifestyle, for lack of a better term, your behavior. So there's no free lunch then? There is no free lunch. And I think we have to get the messaging right because these are very, very effective. Don't get me wrong. They're very, very effective drugs and they should be used.

33:37But we still need to improve everything about what got you there to begin with in order to make sure you sustainably remain healthy. You literally are what you eat. Cambridge University's Giles Yeo there.

Weight Loss Injections

33:50So what is it like to take a course of these weight loss jabs? Journalist Miranda Levy has recently written about her own experience in the Daily Telegraph. Following a bout of weight gain due to antidepressants that she took some years ago, Miranda became increasingly interested in getting back in shape. So she decided to explore weight loss injections with the agent Mounjaro, which also goes by the name to Zepatide. Like other injected weight loss agents, it's only available on a paid for private basis.

34:20And it's very pricey. Her experience was also not altogether positive. So I turned up, there was a very charming young doctor, sort of young, handsome, very disarming. He did the injection, it was fine. You know, I'm not particularly squeamish about things like that. Then he said, great, you know, here's the box, here's the anti-sickness pills in case you need them. That'll be an extra 20 quid. I said, okay. And then he said, oh, I'm going to weigh you now. And I thought, oh, that's a bit weird. Maybe you should have done that beforehand, but fine.

34:51And off I went, and I was really excited. You know, I thought, I'm doing something about this. I feel like a bit of a medical pioneer. I'm going to write about this. It's going to be amazing. So then I got home, and I looked at the box, and I rang my brother and my sister-in-law to tell them. And I said, oh, and I've got my 7.5s. And my sister-in-law went, 7.5? She said, that's a bit high. She said, the guidelines are normally to start at 2.5 milligrams. So in other words, that's three times the recommended dose.

35:24So I went, really? And sure enough, I'd been given three times the recommended dose. And 12 hours later, I started to know about it. In what way? What was it like? So I think I probably started to feel a bit queasy before going to bed, but I had more or less a normal dinner, I think. Woke up, went to have some breakfast, just made myself a piece of toast and jam and a cup of tea, and I just could barely look at the toast. I mean, there's one thing to say, you lose your appetite, but I could hardly, like, put

35:58any in my mouth. It was just, you know, I made myself eat two bites. I couldn't even drink my tea. I had, like, a sip of tea. And, you know, if anyone listening has ever been pregnant, it felt very much like morning sickness. But as the day went on, it didn't get better. It got worse. And I basically could hardly eat a thing for a week and was really, really nauseous. So it just made you feel so bad. I suppose in that respect, it was probably helping to lose some weight, wasn't it? Because you just weren't eating anything.

36:29But it's not terribly compatible with having an active life or doing work if you feel starving, hungry and sick all the time. It was intolerable, really. I mean, you know, there's a balance between losing weight and feeling absolute. And it's a little bit frightening, you know, because it's not like you've had food poisoning or you've been on a car journey and you feel a bit sick and then it's over. It went on for days and days and days. And, you know, as I also wrote in the article, I very quickly got back to the clinic and told them this was going on because it wasn't acceptable to me.

37:02And I now had more facts at my disposal that I'd been given too much. And were they receptive to you going back to the original plan that you'd hatched with them, which was, well, we cut the dose down then? Yeah, the short answer to that is no. So I got back in touch with them on the Friday. So I'd had the jab on the Thursday. So it was by Friday afternoon. So I rang the clinic, sent them an email as well. And they're like, oh, the doctor, Dr. X, he's on leave. He's not back till Tuesday. We're closed till Tuesday. So I had to cope with the whole weekend of feeling like this.

37:36And then Tuesday afternoon, I rang and emailed, was stonewalled. And I finally, the receptionist finally answered. I said, look, you know, I mean, I had no reason to be angry at that point, really. I just said, look, you know, actually, this plan isn't working. You know, I've realised I'm on three times. What is the normal dose? I'd like to go back to the 2.5, please, as we discussed. And the receptionist kind of hedged and hummed and mumbled. And then she said, well, I'm not sure we could get that for you. And I said, what do you mean? She said, oh, I'm not sure the pharmacist can get the 2.5.

38:07And I said, right, I'm coming to the clinic. I'd like to talk to the doctor face to face, please. And so I just jumped in my car and went there. And they said, oh, no, no, no, no, no. You're misreading the papers. No, no, no. They were very, very patronising. And they said, you've read that this is the starting dose for type 2 diabetes. This is weight loss. There have been ex-clinical trials that show that's not the starting dose for weight loss. So I was like, well, you know, I felt a bit sort of steamrolled, really.

38:41And I was like, really? And I didn't want to start screaming around while I was there. So I said, look, OK, whatever the studies say, I would like to go back to 2.5, please, because this is not working for me. And they basically said, no. And I said, what do you mean, no? And they said, it won't work for you. You know, we won't do that. I said, what, you won't do it? And they said, we won't do that. And I said, well, in that case, this isn't the treatment for me. And this isn't the clinic for me. And they looked very, very surprised at that.

39:12Is it still not the treatment for you? Have you gone elsewhere? Have you tried other treatments? Or have you decided this is just not going to work for you, taking these sorts of drugs? Well, good question. For now, I'm trying something else. So I left. And I left in, you know, with a quite dim view of the clinic. But I'd lost four pounds. In a week. So once I started to feel better again, I thought, this is great. I want to continue this. So since then, I've decided to really go for it with diet and exercise.

39:47Because interestingly, I found this inspiring and a springboard. Like, it's working. But maybe if it's not working enough, at some point in the new year, I might go back to Manjaro, armed with this knowledge and to do it safely. So your take home message for anyone who's listening to you is go into this with your eyes open. Make sure you know what you're getting into and be prepared for the fact that it might not work for you. It might be pretty horrendous. It is not a simple walk in the park.

40:18And you may have to change things. Yeah. Be informed. Know what the starting dose should be. Have informed consent. Stand your ground. Know when to say no. Know when to ask questions. And also do expect some side effects, because there are some side effects, but they generally are not nearly as severe as mine and they don't last as long. Miranda Levy on her experience with the weight loss jab, Manjaro, from a private clinic that gave her a very high dose indeed.

40:50Interesting that, isn't it? How do these weight loss injections actually work? Well, John Wilding's a professor of medicine at the University of Liverpool and is published widely on these agents. Physically, I trained as a doctor working in diabetes and endocrinology, which is to do with glands and hormones and so on. And during my training, I saw lots of people living with type 2 diabetes, which is a condition which is largely caused by obesity. And then I spent some time working in a laboratory trying to understand what it is that makes people eat more or eat less and why some people develop obesity and some people don't.

41:28And one of the things that I did in that laboratory was seeing whether different chemicals in the body, different hormones affected body weight. And one of the things we discovered was that this hormone that we already knew was involved in controlling sugar metabolism also is an important signal after we've eaten to tell the brain that we're full. So that got me really interested in this as an area that might help people with obesity as well as diabetes. And what hormone was that? This was a hormone called glucagon-like peptide 1 or GLP-1 for short, which is actually the basis now for treatments for both type 2 diabetes and treatment of people with overweight and obesity.

42:05Where does it come from in the body? Where does it go in the body? And what does it do? GLP-1 is actually made in the small intestine. So it's made in the gut and it's produced when we eat. So when we eat, the GLP-1 levels go up and it goes around in the bloodstream and it goes to two main places where it has its actions. One is the pancreas, where it tells the pancreas to make hormone insulin, which controls the blood sugar after we've eaten. And the other thing it does is it goes to the brain, where it tells the brain, hey-ho, you've had some food. It's time to slow down and eat a bit less now.

42:37Otherwise, you're going to start feeling too full. So these drugs, which mimic that action, they're basically telling the body, stop eating, you've had your fill. It's as though you've had a big meal and you haven't. That's exactly right. And of course, it's one of many hormones from the gut that do the same thing. It's one of the important ones, but we know that there are at least half a dozen other chemicals from the gut that are performing that function. And when we use these agents, are they actually effective? Or in the same way that if you flog a system very hard by giving it fake signals, eventually it becomes deaf to them and ignores them.

43:13So does that happen with these drugs? Or when you use them, does the body remain sensitive to them? And so they do drive a fullness sensation and therefore a reduction in calorie intake. Yes. So these medicines are based on the natural hormone GLP-1, but they've been chemically modified because if we give the natural hormone, which we actually did in some of those early experiments, it only stays in the body for about three minutes because it has been produced continuously by the intestine. So these drugs make that long acting. And the first drugs maybe you had to give by injection twice a day, the later ones once a day.

43:47And now we've got drugs that we can give once a week. So these drugs last a lot longer in their effects than the natural hormone. And they're also much more powerful. We do know from long studies going on for at least four years now in people with diabetes and in people with obesity, that these drugs continue to work with both actions, both to continue to stimulate insulin secretion and to continue to signal to the brain that feeling of fullness, even after you've been taking them four years.

44:18If you've got something that is promoting the release of insulin, though, and you're not eating enough because you've suppressed your appetite because your brain is now being told you're full, do you not end up with lower blood sugar? And is that not a bad thing? No, that's one of the very interesting things about this hormone, because the way this hormone works in the pancreas is that it only stimulates insulin secretion when the blood sugar is high. When the blood sugar drops to below normal levels, it stops working.

44:48So there's a built-in safety mechanism there, which wasn't there with some of the older drugs that we used to treat diabetes with. And how good are they when we start a course of this stuff? How effective is it at suppressing calorie intake, first and foremost? And how does that translate into weight loss and over what sort of time course? So there have been some short-term studies that have been done that have looked at people who've taken the drug for a few days to build up the levels in the body and then looked at how hungry they feel in a short-term laboratory setting.

45:19And people tend to eat about two-thirds of their normal meal size. So that's quite a big reduction in their energy intake in these acute situations. It's probably not quite as strong as that in the real world. There are lots of other temptations and so on around. But what we do know is that with the more recent drugs, particularly ones like semaglutide and tizepatide that are given once a week, we see people lose weight over a period of about six months to a year. And then usually the weight reaches a steady state after that.

45:49But that weight loss is around about 15 to 20 percent of the original body weight. So if you start off at 100 kilos, on average, you might expect to get to between somewhere around 80 and 85 kilos after taking this medicine for a year. The reason why it reaches a plateau, of course, is that as you get smaller, your body needs less energy. And that means that that lower food intake eventually matches your new lower energy requirements. So eventually you stop losing weight, which is a good thing because otherwise we disappear into nothing.

46:22John Wilding from Liverpool University there.

Lifestyle Changes and Public Health

46:25Drugs aren't the answer to everything, though. Arguably, changes in lifestyle, diet and activity levels have played a massive role in creating the obesity pandemic in the first place, which means that effective policies around exercise and public health and what we eat are crucial if we're to halt the trend. Dolly Van Tiliken is from Cambridge University's MRC Epidemiology Unit. And she told me why, compared with yesteryear, waistlines are bulging more now than at any other point in human history. The vast majority of our diets would have been made up of essentially whole and minimally processed foods,

46:59foods that you would recognise as having maybe grown in the ground or come from an animal, etc, etc, may be processed a bit. So we would have foods such as milks and cheeses. These days, though, we have seen the huge ultra processing of foods to almost an unrecognisable state. So you can look at ingredients lists of packets of food in the supermarket today, and there might be not even anything in the ingredients list that you would recognise or just a handful of many of the ingredients that we would recognise. So we've had this huge ultra processing industrialisation of our food system.

47:32And that has basically led to an enormous rate of diet-related disease, food-related ill health in that time. And that's for all sorts of reasons. That's because these highly industrialised foods often contain ingredients and additives that we are slowly starting to find out have very harmful effects on our health. They are designed purposefully in a way to be hyperpalatable, absolutely that delicious, almost addictive quality. They are also designed to be over-consumed.

48:03And that's not just the food itself in the way that it's designed. It's also the way that the marketing is designed. And the fact that you can have buy one, get one freeze on unhealthy foods, which we know isn't about giving people out of kindness more food or food for free. It is about making sure that people consume more and more of those products and have that familiarity with those products built up over time. So there are lots of techniques and strategies that the largest food companies in the UK use to make sure that people consume as many of their products as possible.

48:37And unfortunately, the majority of those products that they sell are unhealthy. Do you not feel a bit uncomfortable then that we're in a position where we're having to invoke drugs, jabs, injections, pills, in order to combat what is effectively a marketing success? We've basically made food over-addictive, over-calorie rich, and people are overeating it as a result. And now we're having to compensate by giving people injections. Yeah. I mean, it's a very bleak way to put it.

49:08And I was having a conversation recently and the idea of a kind of corporate solution by big pharma to a corporate problem made by big food was discussed. And that is another pretty bleak way to look at it. Essentially, you've got huge industries that are making a lot of money from treating a problem that another group of people in companies are making a lot of money from. So it is sad, but it's really important to provide treatment to people that need it.

49:41We are where we are in terms of the system that we have, the food system that we have, and the health consequences of that. So it's really important that no individual is penalised for being part of that system. And if their health has been affected, then they should absolutely get access to the treatment needed. But in order to tackle this issue, I don't see treating our way out of it as the solution. We cannot treat them and send them back to the conditions that made them sick in the first place. We have to see essentially a transformation of our food system so that it enables good health for everyone.

50:13That effectively means policy, doesn't it? It means we need healthy food and healthy eating policy. And something's got to change. So what is the nub of that? Where do we go in order to exact that? Because governments have been told for decades that the population are becoming overweight. This is becoming a huge drain on resources. It's very unhealthy for them. They know that. Why have they not been able to do anything? It can't be an easy nut to crack. The UK government has been trying to tackle obesity and food-related ill health for decades.

50:46It published its first obesity reduction targets in the early 90s. And you won't be surprised to know that they never reached the targets. But since then, we've basically had government after government publishing strategies containing literally hundreds of policies. We've had 689 policies published by the government to tackle obesity and food-related ill health since the early 90s. So a huge number of ideas proposed. And behind that, I would absolutely say that politicians and governments have wanted to

51:17tackle this. It's not that there's necessarily a lack of will to do that in government. There has been attention on this. But it is a very difficult problem to solve. Part of it is because policies are so rarely fully implemented. And there are lots of reasons why that is. But there are lots of good ideas out there. It's just that the nature of government and the politics of it means that ideas don't get seen fully through. And that is where we have to leave it for this week. Next time, the aspiration is to halt new HIV infections all around the world within a decade

51:51or so. Join us on the show to hear how it is being done. And if you'd like to join in the conversation, you can drop us a line at 5livescience at bbc.co.uk. In the meantime, from me, Chris Smith, and all of us here at the Naked Scientist team, thank you for listening. And until next time, goodbye. Welcome to You'll Never Beat, Kyle Walker. Walker is in on the challenge with him. Shoulder to shoulder. Walker scores us brilliantly. Brilliantly. I'm Kyle Walker. Man City and England right back.

52:23And I'm Chris Hughes. And each week, Kyle and I are going to kick back and talk football. We'll tell stories of the beautiful game, dig through Kyle's footballing journey, and find out what it takes to win. A lot. Kings pass. That's excellent. Into Walker. Walker scores! From BBC Radio 5 Live. You'll never beat Kyle Walker. Listen on BBC Sounds.