The doctor and broadcaster, Chris van Tulleken, on why ultra-processed food is making us fat and ill, the team that think they’re close to cracking the male contraceptive pill, and the WHO's drive to get more people vaccinated.
In this episode
00:50 - Ultra-processed food linked to obesity
Ultra-processed food linked to obesity
Chris van Tulleken, UCL
If your lunch consists of a supermarket meal deal washed down with a bottle of fizzy drink then the chances are that you are consuming a fair amount of ultra-processed food or UPF. also known as ‘industrially produced edible substances’. It’s food made at scale and on the cheap. But what saves our wallets can cost us our health, with a growing body of evidence linking ultraprocessed food with heart disease, depression, dementia and cancer. Doctor and broadcaster Chris van Tulleken has been studying them as part of his new book, “Ultra-Processed People: Why Do We All Eat Stuff That Isn't Food ... And Why Can't We Stop?”...
Chris van Tulleken - There's a really long formal scientific definition, and it runs through a couple of pages because the guys who came up with the definition, well, the team that came up with it in 2010, were trying to encompass a whole range of different foods. But the shorthand is if it's wrapped in plastic and it contains additives that you don't typically find in a domestic kitchen like emulsifiers or stabilisers or sweeteners, then it's an ultra-processed food. And the additives aren't really the problem. They're a sign that a product is ultra-processed. Ultra-processing is much more than just additives.
Chris Smith - When did this become a thing?
Chris van Tulleken - I love that question because it was a thing in the 1980s when I was growing up, probably. I think you and I must be about the same age, I'm 44, and my mum would talk about the hazards of processed food. And for a long time people have worried about food processing. And when we process things, we alter them. Humans have been processing food for well over a million years. And processing we think is broadly fine. Ultra-processing came about because some scientists in Brazil were watching this incredible transition in the national nutrition status, where obesity went from being extremely rare, almost unheard of to being the dominant public health problem within a generation in 10, 20 years. But at the same time, people were buying less oil and buying less sugar. They were eating that oil and sugar in the form of biscuits and bread and these products that they decided to call ultra-processed. So what they were doing as scientists, and you'll get this very well and so will the listeners, is they were operationalising an idea, a concept as a hypothesis to be studied and in the next decade, in the last decade, the last 13 years since they created the definition, we've got a huge body of very robust data linking these products to, to really negative health outcomes.
Chris Smith - But why did we start consuming this stuff in the first place, Chris?
Chris van Tulleken - Well, it came about really in the 1970s when it gathered pace. So the problem with real food is it's always been expensive. So in my book I talk about the first example of an ultra-processed product was probably replacing butter with margarine. So butter's always been expensive. You've got to feed a cow grass, milk the cow, shake up the milk, make the butter, the butter goes rancid, and the whole thing's a pain in the neck. It's very expensive. And so even in the late 19th centuries in France replacing butter with something cheap, plant oil became a big project. And once the industrial chemists figured out how to turn a liquid plant oil into a solid fat and emulsify it with water, fake butter - margarine - was born. So margarine was probably the first thing to enter. It's simple cost saving. And part of the definition of UPF is that these products were about profit. And that's going to sound a bit abstract to some of your more scientific listeners, but it's actually really important when you consider food was invented by mainly female domestic scientists over the last few hundred thousand years. And they did it because they wanted to nourish their friends, their family, their community. This food is developed by very financialised companies. And I mean a very particular thing by that, these are companies that have very large owners. They're owned by asset managers. There's a very small number of companies that make UPF and they have absolute legal obligations to generate financial growth and profit. And that incentivises them very strongly to use the cheapest possible ingredients to make the most addictive possible food. And, I think addiction is an important part of this story.
Chris Smith - And what's the evidence that apart from being potentially addictive, that this is actually harming health?
Chris van Tulleken - We've got the usual three layers of evidence that you need to connect a potentially harmful variable with a negative health outcome. So we've got this sort of bottom layer of laboratory evidence and that gives us quite a lot of clues about how the food might be harming us. So we've got studies showing that ultra-processed food is soft and it's energy dense. It's energy dense because it's dry. It's dry because if you take the water out of food, if you dry it, it has a very long shelf life and it's energy dense because that's, that's palatable. And so we think this food is consumed at a rate that overtakes our satiety hormones. So when we eat real food, we have to chew it up. It's got a lot of water in it. As we consume the calories, we start releasing hormones that tell us that we're feeling full. Ultra-processed food is generally consumed much quicker than real food. If you think of supermarket bread versus sourdough bread. Anyone who makes their bread at home or buys expensive bread, and it is really expensive sourdough, will know that it's much chewier and denser than the kind of emulsified foams that make up more than 95% of the bread we all eat. So we consume it quickly and we've got lots of lab evidence about some of the additives like the emulsifiers and their effect on the microbiome, the colorings and some of the other additives and their effect on the brain. We've then got lots of epidemiological evidence. And the big problem for the epidemiologists, the population scientists who studied ultra-processed food, is their question was, is this just salty, fatty, sugary food? Like maybe we could have a simpler definition that just focused on the nutrients. And so they did statistical controls in all of the dozens of prospective studies that have been done looking at early death rates, dementia, inflammatory disease, metabolic disease, heart attacks, strokes. They controlled for fat, salt, sugar and fiber and lots of other things. And what they saw was that the effect on early death, dementia, all those negative health outcomes remained the same once you'd adjusted for the nutrients. So the processing does seem to be important. And then finally we've got a really good clinical trial. It's small, but it was conducted by one of the world's leading nutrition scientists, a guy called Kevin Hall at the National Institute of Health, in the States. And that chimes with all of the epidemiological data. So we've got pretty good evidence over the last decade that I would say there's real consensus among independent scientists. The people I work with at the World Health Organization at UNICEF, the scientists who aren't involved with the food industry, my colleagues at UCL, colleagues at Imperial, lots of colleagues in France, so big institutions around the world, there's real consensus building that this is the primary driver of pandemic obesity, this category of food.
Chris Smith - And what are we able to do about this? Because the whole world is effectively addicted to this sort of food production system. And it's going to take ages to unpick this.
Chris van Tulleken - My book proposes to the reader. There's a kind of eat along experiment that you can get involved with where you are being part of an experiment anyway, so eat along and as you learn about the food, it may become disgusting. Ultimately, I don't think it's really fair to ask individuals to change. This is the only available affordable food for most people. We need the government to label this food and we need to make real food much cheaper and we need to dramatically change everything about our food system. Most of all, we need to uncouple policy makers like the government and charities from the food industry. At the moment, the food industry has almost total capture of policy makers and all the basic research. So we need to disentangle that mess first.
09:11 - WHO 'big catch up' to close vaccine gap
WHO 'big catch up' to close vaccine gap
Kate O'Brien, WHO
They’re dubbing it “the Big Catch-up” – it’s an initiative to vaccinate millions of children and restore immunisation progress lost during the Covid-19 pandemic which has seen millions of children miss essential jabs for lethal diseases like diphtheria and polio, setting back vaccination progress in many place by decades. Kate O’Brien, Director of the World Health Organisation's Department of Immunisation, Vaccines and Biologicals, has been speaking about why it's so important…
Kate - The first thing to say is this is not a concentrated problem. This is not like there's a small number of countries where this happened. There's over a hundred countries where there's backsliding. And really we call it historic backsliding. We've never seen something like this before. In 2021 alone, there were 25 million children who missed out on at least one essential vaccine. 18 million of them didn't get a single dose, not one dose at all of immunisation through the routine program. This takes us backwards to levels of immunisation that we were getting in 2008. So in three short years, we have basically lost the performance that was built over a 15 year period.
James - That's enormous. And as Bill Gates puts it, in short, 'vaccines work'. They save millions of lives and improve the quality of life of millions more. So I wonder if you could kind of speak to the potential consequences, if there's a failure to react to the millions that have missed out on vaccinations over the past few years.
Kate - We see a rising number of outbreaks of diseases like measles, diptheria, polio, yellow fever, for instance. In the past 12 months alone, there are 33 countries around the world that have had what we call large and disruptive measles outbreaks. Those are the big ones. There are smaller measles outbreaks that are also occurring. But that's just one example of what this means for families, what it means for kids, what it means for a community. Children are dying as a result of this. Even if they're not dying, they're getting serious illnesses that impact their life going forward. They may have long-term consequences from diseases that they get. Paralysis from polio, neurologic deficiencies, neurological impacts from meningitis. So those are some of the things that are happening, these rising number of outbreaks. And they're spreading into additional countries that these are the lives and the wellbeing of kids for the future.
James - Yeah, I mean, you've outlined there just how important it is that we close this immunity gap. So that's where 'The Big Catch Up' comes in, isn't it? This year's world immunisation week dedicated to responding to this deficit.
Kate - So we really have rung the alarm bell, and we're calling this the big catch up. And there are three things that we really want countries to do and we want people to do. So the first is to catch up those kids who missed out on vaccines during the course of the pandemic period, setting up programs that will immunise kids even if they're a little bit older than the age at which they would otherwise have been vaccinated. The second thing that the big catch up entails is restoring the immunisation program. So for the kids being born in 2023, we want to make sure that the immunisation programs in every country around the world are performing at least at the levels that they were before we went into the pandemic. And then the third thing that the big catchup is really pointing to is that every single country can do better on their immunisation program. And we had already set a goal with every country around the world for what we would achieve by the end of this decade, by 2030. And so we're really asking for countries to get back on track to reach that trajectory. And it does mean that individuals have actions that they can take. It means parents should ensure that their children are up to date, that they didn't miss vaccines during the course of the pandemic years. And also being advocates with your family, with your friends, with your community, sharing information that is accurate information about vaccines. And then at the national level, it's really about using resources of governments and redirecting those resources to support doing more through the immunisation program.
James - I think what you're saying, everyone can get behind. I just wonder if, given the sort of long-term nature of this sort of project, how it's going to be determined whether it's been a success. What will it mean to have been caught up?
Kate - The most complete data that we have is for 2021. And in 2021, three quarters of the world's children who didn't get any doses through the routine immunisation program, were living in 20 countries. We're going to be paying special attention to those 20 countries to give all the support that we can, both financial support, technical support, advocacy. The way that we're going to know whether or not this is working is, first and foremost, the evidence that the countries have, the data that the country has. So we'll have a pretty good feel for the impact of the big catch up as we go through 2023. The second thing is that we will start to see a quietening down of some of the outbreaks. We monitor outbreaks really carefully, and so we do see over time whether outbreaks are increasing in number, increasing in spread, increasing in size. So this is something that we track really, really carefully.
15:49 - Male contraceptive drug targets sperm protein
Male contraceptive drug targets sperm protein
Jon Oatley, Washington State University
Oral contraceptive pills for women have been available since the 1960s but - until now - an equivalent for men has eluded researchers. However, scientists in the United States say they have made a major breakthrough. By looking at the testes of many different mammals, they have found a gene, catchily titled ‘ARDC5’, that is switched on exclusively in testicular tissue and used only for making a protein involved in sperm production. So the thinking is that, if they can find a drug that temporarily blocks this protein, they can throw a spanner in the sperm production works, but without affecting any other tissue in the body, reducing the risk of side effects. The senior author on the new study is Washington State University’s Jon Oatley…
Jon - We know in an experimental animal model, which we tend to start with mice, that when we inactivated the gene, we took out the ability of the gene to make the protein. And the only impact that we found by studying both male and female, what we would call knockout mice, was male specific sterility. And it wasn't that they couldn't make sperm, that the sperm that they made were not produced normally and so they were unable to fertilise an egg.
Chris - So that means then that's a potential target. So would your idea now be, well if we interrupt the function of that gene, we don't want to take it out in an average male human obviously, but if we interrupt it, then we should get the same sort of outcome.
Jon - Absolutely. So in human contraceptive development, we would be looking for a strategy that would inhibit the molecule or the protein that is encoded for by that gene. In other animal species, there may be a strategy of inactivating the gene itself, but in humans it would be targeting the molecule that's produced by the gene. So we wouldn't be making any changes to the DNA. We'd be instead targeting the protein that is produced by the gene to make it not functional.
Chris - And does it look like something 'druggable'? Does it look like a target that is amenable to you going in with some small molecule that will hit it and turn it off temporarily?
Jon - We believe it is targetable because ARDC5 is a molecule that's in a larger family of ARRDCs. And based on what we know of the function of the other family members that they play roles in their localised and parts of the cell, that should be druggable. The thing about ARDCA5 is that it's unique in its molecular structure compared to its other family members. So we do believe that we'll be able to design a small molecule inhibitor that is selective or specific to just ARDC5.
Chris - Have you got any candidate molecules yet?
Jon - That's where we're at now. That's what we're screening for. So we're developing a high throughput screen strategy to screen through compound libraries to get a hit. And if we get a hit then we're off to the races in doing drug design.
Chris - And how long do you think this is going to take?
Jon - Yeah, that's a great question. There's lots of boxes, complex boxes, that need to be checked when you're developing a pharmaceutical for male contraception. And I think given sufficient resources, given sufficient tools, I'm optimistic that we would be able to get there in 10 years.
Chris - That's quite ambitious and encouraging at the same time. But people have been trying to do this for decades, ever since Carl Djerassi came up with ways of making some of the female hormones that gave us the female contraceptives and they haven't succeeded. So why do you think you will get there where many others have failed?
Jon - Absolutely. I think there's a lot of hurdles when it comes to trying to develop a male contraception and one of them, in addition to the ones I've talked about, is the reversibility nature of it. And so some molecules, if you're targeting them or if you're targeting the endocrine system, hormonal system, draw back the sperm production process so far in its development that the chances of reversibility are potentially compromised. One of the advantages or unique things that we think ARDC5 has is that it's involved just in that final step of putting sperm together, it's like a car factory in putting sperm together, it starts at a very naive state. The cells do and they need to be assembled along a kind of factory line. So if you think about it like a car assembly factory where ARDC5 is playing a role, we think of putting the tires on the car to get it ready to roll. So if we're inhibiting just that process, the chances of reversibility are pretty high.
Chris - Have you spoken to any drug companies? Have they been on the phone to you to say, 'this looks promising. Can we talk?'
Jon - I've had some initial emails reach out and some other commercial interests and we do have a provisional patent filing in the United States for this. And so we're starting to develop some of the commercial channels that might be able to get this out of the lab and into the public domain eventually.
Chris - Is that not going to be a frustration though? Because there's been a lot of difficulty in the wake of the human genome project, for example, around patenting what are effectively genes and gene targets. So are you not going to run into that problem that people will say, well you've just found a gene and you can't really protect that?
Jon - Absolutely. That's one of the things that we're going to be working towards is how we make those arguments and those claims for this target. And so we've got some experience from the animal world in doing this because we've been able to successfully patent some applications on other gene targets in domestic animals. And so maybe we can use some of that experience to get our claim sets approved for human gene targets.
21:20 - Mars' core composition confirmed
Mars' core composition confirmed
Jessica Irving, University of Bristol
For the first time scientists have managed to measure what is inside our cosmic neighbour. By using a seismometer - a tool that measures tremors - aboard NASA’s InSight lander, and relying on Mars quakes and even a meteor impact to shake the planet, the University of Bristol’s Jessica Irving and her team were able to use the passage of the vibrations through the Martian ground to confirm the predicted models of what Mars is made of.
Jessica - So the seismometer is similar to the seismometers that we would use on Earth. There are actually two in one big instrument. So doing seismology on Mars was always a part of the InSight plan, if Mars cooperated.
Will - Listeners to the show might remember a programme we did a short time ago based on working out the Earth's core by using vibrations of tectonic plates to work out composition of the inner Earth. Is that the same as what you did on Mars?
Jessica - They are the same techniques and actually many of the seismologists that have been working on Mars also work on Earth data. But on Earth we have seismometers on every continent, but on Mars we just have one seismometer for the whole planet and we also have many, many fewer quakes on Mars than we do on Earth.
Will - How does a Mars quake happen then?
Jessica - A Marsquake, so far as we've seen them, is just a small quake of the sort you'd get inside a tectonic plate. They're not very big, but over the lifetime of the InSight mission, we've managed to detect more than a thousand mask quakes. There's another sort of seismic source that we're also able to use for Mars. And again, this is one that we hoped would work and we couldn't guarantee it. And that's the meteorite impact on the surface of the planet.
Will - That sounds like a pretty big meteorite then if it's going to be able to reveal data about the entirety of the core of Mars.
Jessica - Yes, and we needed a really big meteorite impact to make that work. And we got one! We were really lucky. On the far side of Mars from where we have our seismometer, we had a very large meteorite impact. The impact made a crater that was about 130 metres across and the dust and fallout around the crater was so big it could be seen from space.
Will - And what did it reveal about Mars' core?
Jessica - So Mars' core has a radius that's about 1800 kilometres, and this is similar to, but a little bit smaller, than previous estimates made using different sorts of techniques, but we've not actually managed to get waves that have been into Mars' core before, so we were really happy to have these new signals to work with.
Will - Inevitably, when we talk about Mars, we end up comparing it to Earth. Is there a difference in the composition of the two planet's cores?
Jessica - What we see is that Mars's core is about half of the radius of the planet, and Earth's core is about half the radius of the planet. But Mars's core has a slightly different composition. They're both mostly iron, but Mars's core has about twice as many light elements in it as Earth's core does. So light elements are things like carbon, oxygen, it's probably a lot of sulphur in Mars' core and we think maybe a sprinkling of hydrogen as well. So different compositions that probably reflect both how the cores were formed and the building blocks they were formed from. As our planets grew.
Will - If they are both iron and yet Earth has a magnetosphere and Mars does not, do you think that the slight difference in composition is responsible for that?
Jessica - There are probably multiple different things which have meant that Mars doesn't have a magnetic field today, but Earth does. Certainly we know that Mars used to have a magnetic field. So billions of years ago there was a magnetic field not too dissimilar to Earth's and that would've been good at protecting the atmosphere of Mars. But now that magnetic field has gone, Mars is relatively unprotected and certainly we know that the magnetic fields are generated inside planetary cores for planets like Earth and Mars. So there are definitely reasons to think that what's happened to Mars' core over its history and what happens to Earth's core over its history have had different roots and different evolutions to give us these different setups today.
Will - What is the overall use then of understanding these differences between the two planet's core compositions?
Jessica - If we want to think about planetary habitability, then understanding if we have a planetary magnetic field that is present and likely to stay there is a really important long-term goal. But as well as that we actually get to look back in time and think about how planets grew and how planets formed. And we can look outwards into our solar system and see some moons of other planets and think how their internal setups work and how might we understand how they've evolved and changed through history?
Will - Is that the plan then? Are we headed out to other bodies in the solar system to do the same?
Jessica - I think it would be the dream of many seismologists to do the same across the solar system. So the seismometer on Mars has unfortunately died. It ran out of power because its solar panels got completely covered in dust. But there are hopes that there will be seismology missions to other planets and especially moons in the near future. So there is a mission which NASA is looking at to run as part of the Artemis missions. That's the far side seismic suite, which should put a seismometer onto the Moon. That hasn't been done since the Apollo missions. And there's also a mission which is hoping to put a seismometer onto the moon Titan, way out at the far end of the solar system. So that will have some seismology results if everything goes to plan as well.
Will - Very exciting then. Good time to be a seismologist in space.
Jessica - It's a wonderful time to be a seismologist anywhere with any of this data available.
27:06 - Why do we find new solutions after a break?
Why do we find new solutions after a break?
James - Great question, Jo. When continuously doing the same thing over and over again, our brains become tired and non-responsive. Have you ever experienced when you repeat a word over and over and over, it tends to lose its meaning and you might even get to the point of wondering how it ever seemed like a proper word in the first place? This is called semantic satiation. Alejandro Lleras, Professor in Psychology from the University of Illinois is here to help me explain…
Alejandro - Hi James. One interesting aspect of the ways neuronal activity fails is that it works in a sort of neighborhood manner. If I ask you, for example, to quickly name all the vegetables that you know, you will start strong, and after uttering several vegetable words, you will suddenly find yourself stuck. well before you finish saying all the vegetables you do know. Words that usually would come to mind (like avocado or cucumber) might simply not be there, in your mind, for you to utter.
It's not that you do now know these words, it's that the continual retrieval of the same sort of information from your semantic network is consistently activating all the words that you did manage to say, and this effort gets those concepts, as well as nearby ones "tired", so to speak.
Alejandro - Your brain feels it has exhausted all possible vegetable names because (a) you were doing the same thing over and over again, and (b) these acts of retrieval tired not just the specific instances that you did retrieve, but also some of their nearby neighbors.
If you wait for a while, some of this neighboring neural fatigue will lift. Changing what you are doing will also relieve the fatigue on the goal itself: it will seem easier to re-engage with the task of naming vegetables, if for a few minutes, you do a completely different task.
Alejandro - This is exactly analogous to what is happening with your Sudoku solutions. You keep trying to do the same thing, and activating the same set of (non-working) solutions, which has the effect of basically hiding from you neighboring thoughts or solutions that you could have had otherwise. A break will lift this neuronal fatigue. You will be able to re-engage with full vigor on the task of solving your puzzle, and some of those recently hidden thoughts will be free to enter your awareness, suggesting solutions that you have not tried before. Voila!
James - So, Jo,. When doing the same thing over and over again, neuronal activity can become tired and non-responsive, leading to nearby concepts becoming difficult to reach for. Taking a break and doing a different task can relieve this neuronal fatigue and allow for re-engagement with the original task, potentially bringing to mind solutions that were previously hidden, just like on your Sudoku puzzle!
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