I put together a series of free lectures this year, and you know, they weren't going to be a laugh feast, were they? I started off with the environmental footprint of war, and I think most people got behind the idea that war was a fundamentally bad idea. So that wasn't okay, yeah. Then I did AI and our modern digital lives, and certain demographics were a little bit uncomfortable, and people with laptops were furious, I think, when I told them quite what the what this sort of carbon budget of their beloved laptop was, and that it would take them 10,000 years to become neutral. That was a bit of a discovery. That upset them. And so, just as a heads up, I have tried in this talk to find another sacred cow which will upset as many of you as I possibly can. It will be in the second half. So if you're enraged early on, yeah, it's not a good sign. So when I was thinking about the third lecture, one of the things which has really been focusing on my mind recently is really the interaction we have with a global aging population. This term which people throw out very glibly, with no real detail or philosophy behind it, which is healthy aging, whatever healthy aging means, and how that actually interacts with the health of the planet. Is it good to have a healthy aging popular healthy words of question, isn't it? What is healthy aging? So that's the question I want to delve into today. And I'm not here to give the pharma industry a kicking. Because I was thinking about this as I was putting the talk together. You know, um, I'm from Imperial, and sort of like 1928 is when penicillin is invented. Yeah, so we're coming up to the 100th anniversary of the discovery of penicillin. And a hundred years ago, quite a number of you young people wouldn't be here because you wouldn't have made it through childhood. Yeah? Um, and parents in this room would not have statistically made it to this stage without having lost and buried some of their children. So the gains in healthcare through medication, through the discoveries of the pharmaceutical industry have been revelatory. They have changed our interaction and the way in which we live for the good. But now I think we're beginning to pivot away from dealing with medical emergencies to sustaining health and extending life. And at that point, I think it's worth asking the question: where is the pivot point between that having a detrimental effect on the planet as a whole? That's the philosophy behind my talk. Um that's fundamentally the image of the idea. Now that's going to allow me to deal with a few things which I think are kind of not really talked about. So let's talk about aging and the difference between aging and healthy aging. And I'm going to start off just by really focusing firstly on these population pyramids. There are three population pyramids here. Two of them are real data, one of them is a projection into the future. So we have 1966, you can see it has a nice wide base, lots of young people, and it narrows up to the top as the old people get older. The number of men and women become fewer and fewer. Get to 2016. You can see the boomers are moving up that demographic. We can see it's getting fat in the middle, and you do the projection through to 2066, and you can see actually we have a large number of older people. In fact, you know, the key areas we're really looking at. I'm just trying to get this to come up. There you are. We can see that expansion between 75 and 100. Um, that's a really important expansion in the population in terms of thinking about future healthcare and thinking about future health economics. Those individuals are not cheap. Yes? They are the major users of our health system. So that's kind of the direction of travel. And then I thought what would be quite interesting is to give you the idea of sort of perhaps what I think I think of as a statistically idealized life course. And what you have here are sort of survival curves across time from 1900 through to 2017. You can see the orange line, we have a big drop because there's a high lot of high rate of childhood mortality. And then we kind of have it's kind of a slow fade. You have a few good years, and then it's just a gradual decline. Yeah, and I think many people think of that in terms of how aging works. What we really want is what's referred to as the rectangularization of the health course, which is you live healthy and well for quite a long time, and then you get ill and you decline very rapidly, and then you die. Yes, you don't linger, you're not expensive, you don't have to have expensive, poor quality life for decades. All of the money can be spent on palliative care to support your end-of-life journey. Preferred, the rectangularization of the life course. So this sounds, and if you look at that, it looks as though we're getting there, doesn't it? It's been nudging gradually towards that sort of rectangular shape. But now we can have a bit of a reality check. Because for years I could give a talk like this and I could begin it by saying we're all living longer. Only, of course, we're not. Not anymore. So this is this was published recently, and it got quite a lot of coverage. This is looking at years of healthy life. So these are years of living without a chronic condition which is impacting on the quality of life. And you can see in 2022 to 24, for women it's now 60.9, for men it's 60.7, and it's come down. So actually, the years of healthy life in our population now have dropped across the board by about two years. And you might think that's quite good, but if I took this back to 2010, it would have gone up again. So we've actually something quite dramatic has happened in terms of the years of healthy life we have in the United Kingdom. And the reason that becomes important is when you actually look at life expectancy. So these are from the Office of National Statistics. So the average life expectancy of a woman 2024 is 83 years. So what does that mean? According to this, she's gonna 23 years of unhealthy life. The man's going to suffer about 19 years of unhealthy life, uh, purely because he dies earlier than the woman. So, you know, you know, that's that's the only reason. So that decrease in our healthy lifespan matters because we are still going to be living for a long time with chronic disease. This is the actual data when you disaggregate it. It's a little bit difficult. We go to the top, we have the total figure in the UK. That little grey box at the top is telling us what the sort of years of healthy life were in 2019 to 21, and the blue is what it is now. So you can see across the board it's shifted. It's even more shocking if you go across and you look sort of towards Wales and women in Wales, you can see there's a there's a huge drop. So this is happening in plain sight whilst we are celebrating the successes of our healthcare system, and everybody's obsessed with healthy aging and wellness, which I will probably have a rant at at some point, just as a fundamental concept. So, something is happening. We're not living as long. Life expectancy has fallen. We're not living as long healthily as we have in the past. And it's not everywhere. This you wouldn't have this pattern in Europe. Continental Europe doesn't show this pattern. The United Kingdom and the United States show this overall pattern. So it's kind of depends where you are, because you can see this in different places. So, what's going on? One way of unpacking this and thinking about life course, and I've tried to give this a kind of global and historical perspective, is to introduce you to, I think, a really critical concept in how we think about aging and the way in which populations live and populations die. And so I'm going to introduce you to the concept of the epidemiological transition. Um, this idea was published by the Egyptian epidemiologist Abrul Omran. And essentially it's it's very straightforward, it's just an observation. You know, in the past people died of infectious disease, and then we got antibiotics, and they stopped dying of infectious disease, and they lived longer because they lived longer. Now they die of non-communicable disease mostly. And there's a kind of graph here, and it kind of illustrates that quite nicely. So if you look down at the bottom, there's a sort of teal green triangle, and that's tuberculosis deaths. So you can see tuberculosis dates from 1860 through to 1960, almost completely gone. Above that, we have a light blue zone. That light blue zone is just infectious disease generally, so we can see it's coming down. And then we begin to see the one above it is diarrhea, that sort of light blue colour, and then we get to green. The green one at the bottom there is cancer, the really big yawning one, which increases, that's cardiovascular disease. Above cardiovascular disease, the burgundy colour, that's stroke. So we can see that over time, fewer people are dying of infectious disease, more people are dying of the diseases of age, the non-communicable diseases. That's the epidemiological transition, and that has an impact on the sort of dynamics of your population. So that's illustrated here. So as the death rate falls, because people aren't dying predominantly in childhood and they're not getting infections in childhood. Initially we have this early expanding population. The birth rate stays constant, but then after a while, as people live longer, they can make choices to have children later. The birth rate begins to decline, and over time you sort of move into a stationary phase. The United Kingdom at the present moment in time is probably in that stationary phase, yes, where you know we're kind of just at the tipping point where the birth rate is probably not sufficient to meet the death rate, and it's going to change as we go through that. And that's a that's kind of where we are in the present moment in time. But behind those figures, we have the really big changes and the things which I think are important, which is globally the improvement has been in the under five-year-olds. Um, but the uh 70-year-olds, they're still at the top of the list in terms of the house, it hasn't changed so dramatically. So, disease and the nature of death changes, and we tend to think of that, or we often think of that through the lens of the UK, because I'm in the UK, and we can put a kind of chronology on that and a date. But I think it's also worth bearing in mind that it's not the same everywhere. So that would be, and I'm going to start talking about Dallas now. DALIS are disability-adjusted life years. They look at the amount of life which is lost in a population and also the amount of years of living with a disability. So they're a really good measure of sort of like the cost of disease at the population. And so here we're looking at Dallas Years of Lost Life, and this is in 1990, and it's just to make the point that they're it's patchy, it varies where you are in the globe. And if you go across time, you can see sort of that there are changes, but there are still places where sort of like you know, we still have significant losses of Dallas in the population. What are people dying of? Well, here's a list. Um, you can't read it, so let me just give you some of the headline figures. 2019 90, we have 320 million cardiovascular deaths in 2023. That's up to 436 million deaths. Neonatal deaths are going in the other direction because we're getting better at that. Mental disorders are going in the other direction, and a lot of that isn't isn't mental illness, that a lot of that is sort of dementia because of the aging population. So we do have these profound changes, and we can follow those through time, and we can begin to see how they all stack up. And this is just like a little kind of layer cake of things which are going to kill you. I told you I don't do tier four talks, but again, it's showing that the diseases of age are going up, and the diseases of infectious disease are going down, with obviously a clear little spiky point during 2020 when we had COVID in the lower panel. Okay, so that's where we are. But the population is getting older, but it's not so healthy. And on top of that, of course, we have this concept. And that's the concept of multimorbidity. Um we often, and in the medical profession, it happens the whole time, people are labored by having one disease and they're treated for one disease, but nobody over the age of 15 to 16 to 70 only presents with a single disease. At the between 45 and 60, about 30% of people will have two coexistent conditions. We could imagine that could be a bit of congestive heart failure, maybe some bronchitis if the individual had smoked. By the time you're between 65 through to 80, you're probably up to 65 are presenting with three comorbid conditions: cardiovascular, respiratory, um skeletal disease, osteoporosis, something which doesn't get nearly enough coverage because of the impact it has on health and the cost uh to people's quality of life and to the National Health Service. And by the time people are over 85, really they have you know up to four comorbidities. So this matters because it means as these individuals are getting old, uh, these diseases have to be managed. And to manage these diseases, you have to use more and more drugs. And so we move into the realm of polypharmacy, where it's quite feasible that somebody who is 85 years old is on a regular basis with the little pill box taking 10 pills a day, five pills potentially for the things which are wrong with them, five for the symptoms related to the drugs which are helping to deal with the other five things which they have, yes? So suddenly you see that what we have is a population with disease, and we are medicating the life course over decades, and that that has economic consequences, but not many people think about whether it has environmental consequences across the board. It's absolutely teppered to the standard of living and and and to economics. Um, you know, there are still places in the world who haven't undergone the epidemiological transition. There are still places in the world where the childhood mortality rate is like the 1890s in the United Kingdom. So it's quite patchy. And you can demonstrate that, and I'm trying to get to just the idea of this through this diagram. I've taken this, this is from World Bank data and also from the last global burden disease. So in 2025, they updated all the works on the global burden of disease. And this is just looking at Dallas, so this is disability adjusted life years again per 100,000 people relative to the GDP per capita on the on the x-axis. And we have 1990 and 2023. And so what you're wanting to see is that basically the DALIS go down as the investment in health goes up, because you can see more money's being spent, so there are fewer disability life years in the system. And what's nice about this is you can track India and China from the 1990s, and because of the economic growth, you can see by 2023 they've shifted dramatically in the other direction. As wealth and treatment options become available in that country, you begin to see a reduction in the disability years. And the economic signal here is absolutely, absolutely critical. It determines a large number of things. So this is the pattern. It's not terribly equal. There are massive problems globally, but I again I do think we have to sit there and say, well, let's look at the positives, okay, and let's just track what has happened over the last hundred years and into the future, which has allowed the population to live into their 80s and 90s, and a small fraction of them to get to 100. I'm not one of these people who believe there's going to be a like a glut of centurions, yes, um, in about 50 years. I mean, it's going in the wrong direction anyway, if you look at the statistics. So let's celebrate what we achieved. These are just a few kind of landmarks, but let's think about what they achieved, and then we can unpack what the consequences of these things have been on a planetary scale. So I'm starting with penicillin, say discovered in 1928, not really deployed until 1940 as a product. We can move forward to 1935, that's when we begin to see the first synthetic antibacterials appearing. You know, this is quite a dramatic movement. 1952, we have the first sort of psychopharmacy products, it's anti-sort of psychosis drugs. And in 1960, we have the licensing for the first time of the oral contraceptive in the United Kingdom. Now that's huge. This isn't really medication per se, this is control of the life course, yes? This is a this is freeing, separating sex and reproduction, opening up options for people to live their life. So this is kind of like medication and treatment towards a different way of living, not to cure a disease per se. So you could argue this is the first time in which we have a kind of lifestyle medication. The other ones are treating actual conditions which are likely to kill you. 1964, Sir James Black, Nobel laureate, um, a wonderful scientist, uh developed beta blockers, our first really sort of standard sort of cardiovascular treatment option to begin with. 1968, salbutamol. So we begin to see inhaled corticosteroid treatments and beta agonists beginning to appear for airway disease. 1982, we move into the first sort of fully synthetic engineered insulin. I mean, a hundred years ago you didn't survive being diabetic, yes? So thank goodness for the developments that have been made. 1987, statins. Statins, the market is huge. The number of men in middle age on maintenance statins globally is astronomical. But again, it's managing, it's managing cholesterol and a risk factor for a disease to try to even out the risk factors of later life. And if you look at cardiovascular deaths in you know developed countries where we have proper polypharmacy for hypertension, for hypercholesterolemia, then those rates have fallen precipitously. It's been tremendously successful. We can move on. We have our first treatment for leukemia in 2021 effective. We begin to see mRNA viruses turning around in 2020, supercharged by the COVID epidemic. In 2021, we begin to see the GLP agonists coming in to deal with the obesity epidemic. I have views on the widespread use of GLP agonists for lifestyle. Adjustment and I do within that hold the view that obesity is a complicated disease. But you'll find out why I have some issues with that as we go through this. And as we move on, I've skipped on, I've added two years because it's very symmetrical and I wanted to go to 2028. Um, we are going to begin to see this terrible term being thrown up a great deal in the media where people talk about personalized medicine and CRISPR-based technologies, and it will sound very, very exciting, but to deploy it at a population level is going to be almost impossible. And I do worry that the direction of travel might be very, very sophisticated medication for the billionaires and not very much of anybody else, because these are very, very expensive treatments. So look, the landscape has changed. Those landmark changes in the way in which we interact with drugs and disease has extended life, it has improved the quality of life. I have obviously haven't dealt with any of the sort of like anti-anxiety drugs. I will deal with them in a late second half of this talk. Now, that means there are lots of drugs out there, and there are many, many people taking drugs, and many people taking very impressive uh numbers of drugs with very, very rigorous and disciplined uh procedures. And it made me loop around to the very first Gresham lecture I gave, which was almost three and a half years ago, but I introduced the audience to the concept of the exposome. Now, this is going to feel like a tangent, but bear with me, it's not a tangent, it will all miraculously come together. So the exposome is an interesting concept. It argues that your health is largely shaped by your environment in its totality. Yeah. So things such as air pollution or noise or stress or adverse early life experiences all contribute towards increasing your risk of particular diseases. And the science has actually come a long way. It's 21 years old, this topic. It was only sort of fomented 21 years ago. But the idea is if you can understand the totality of the environmental exposures an individual has from conception all the way to the point when they manifest disease, you can begin to unpick how the environment shapes the diseases that we have. It's almost the counter-argument, it's often framed as the counter-argument to the genomic medicine field. You know, when when we went into the post-genomic world, everybody thought that we knew, when we knew the genes, we would work out disease. And then people realized, particularly for the non-communicable diseases, most of the risk isn't genetic. Most of the actual risk comes from our environment. And that would also include diet, yes? So it's everything. Now that means it's a really big nebulous concept, and it comes in different flavors where you measure sort of like toxins in the environment and then you relate them to health, or you go into people's sort of blood tissue samples and you look for biomarkers to follow disease progression and you try to link it. There are lots of ways of doing this. But it occurred to me that we've never really put drugs on this. And perhaps that's because drugs don't seem to work, don't they? Because we we use drugs to interrupt the progression towards disease or to reduce the symptoms we would experience as we move towards disease. But I'm just going to drop it in because we live, I think, in a highly pharmaceuticalized exposome. And it's there. And most of the time it's doing pretty useful and good things to maintain our health. However, your drug doesn't stay your drug for long when it gets taken up into your body, it's metabolized. So your drug will often become a different compound. It will often become many different compounds. And some of those compounds will actually be very effective as your target treatment. But some of those metabolites, I'm afraid, are just going to get released into the environment in your urine and your feces. And at that point, your drug has now become an environmental issue. So we now have drug metabolites in the environment, okay? And they're within your body, and they escape outside your body into the environment. And so the compound we knew so much about has been metabolized, and generally speaking, we know all about the metabolites as well. But unfortunately, then the metabolites get metabolized by the microbiota in the environment and get broken down by chemical processes, and so that kind of like cloud of different chemical species grows, and we really have no idea how toxic many of those components are. But it does mean that the thing moves around. It means that those metabolites which have entered the environment can come back and re-expose us. And when they come back and re-expose us, the question is what are the impacts on our health? But that's also a rather narrow view. Because they don't necessarily have to impact on our health, they may impact on the planetary health. They may impact on biodiversity, for example. And that's equally as important because we know that if you deplete biodiversity, that itself seems to be associated with health effects. So the drugs we use do not cease to exist at the moment we have taken them. They have a legacy in our environment, and there are questions which I think are worth asking. So this is thinking about that exposome concept again. And I have five lines. Yes, it is five, I remember correctly. Um, and they relate to different types of exposures, because if you think about it, it's kind of a mad and crazy idea to assume that I could work out everything you've been exposed to every minute of your life from the point you were born to now. It's never going to happen. So generally speaking, you can think about this in terms of how people live their life. So one, that would be sort of like that. That would be an exposure during pregnancy. Yeah, only occurs during pregnancy. So there's a pattern, that's the thing. And then number two, be something which you're exposed to all the time, and there's nothing you can do about it. That could be air pollution. If you're in a city, live in a city, there's very little you can do about the air pollution in that city. The third one, look, it's very low until about the age of 18, and then it goes up and then it stays, and then at about the age of 60, 65, this dates, this diagram, it should now be about 67. Uh, it goes back down and then it's flat. That's occupational. Yes? Exposures related to your occupation. A little wiggly green line at the bottom, seasonality. So that's like pollen. But the interesting one's the sort of orange line, and you can see it goes up, and then there are little peaks, and then from about the age of 50, it goes up and then it goes up and then it goes up, and that's medication usage. So if we're really interested in understanding how the drugs interact with our health, and about that, that loss of healthy life within our population, this is the point I think that we need to look at. And within that, there are these two terms which I think I'm just gonna keep on going on about polypharmacy. Um, you know, it it would be fine if I'm gonna give you some examples of drug regimes people take in a second. It would be okay if people had their little pill boxes with the drugs they'd been given, if they didn't then go to uh sort of a homeopath and to a shop and take vitamins, and then somebody who suggested they take a herb which has been brought in and export, you know, imported from Tibet. Um, so on top of the drugs which people take, which we know do something, people are also taking a whole plethora of jobs. I was going to try to go and find old relatives and take a photograph of their sort of bathroom cabinets, but it felt as though it was too invasive. But I must say I've never been less than amazed at the amount of medication and the variety of things which they have by the age of 70, 80, and 90 years old. So, polypharmacy is huge, and we have a process where we are now a population who is pharmaceuticalized. It is one of our most common exposures. Our interaction with the drug exposome is probably one of our most dominant exposures, and we don't know that much about it unless it's helping us to alleviate disease. And it affects all of us. And I thought to illustrate that, what I would do is I would create some sort of archetypes. And just to give you another warning, this is when I'm gonna walk you into the thing you'll hate me for. If you don't hate me already. Okay, let's start with this young fellow. He's clearly got asthma. Um boy, probably got diagnosed around six, seven, eight years old, difficult to control, asthma. He's on an inhaled corticosteroid, and he's going to be on that inhaled corticosteroid for his life because it's not going to be a resolvable condition. Um, he's also got allergies, so he'll be on sort of antihistamines. And but there's an interesting sort of feedback problem here because he's using an inhaler which has climate-forcing sort of propellants in it. So his asthma, if his asthma was being triggered by air pollution, um theoretically, some aspect of this product itself is feeding into the same process which is leading to the pollution which is leading to his asthma. Now, that's not to say this isn't absolutely necessary, but it's a kind of just think about it in a different way. Where does it go? Where do all these inhalers go when you finish with that? I know there are now sort of mechanisms for having them recycled, but then where do they go when they're recycled? Have you really thought that through? So he has an essential medication for his life. But he's going to be taking that medication for the duration of his life, and it comes already with a I'm gonna use this term a little bit, an environmental rucksack. How much it costs in CO2, how much it costs in raw material. Fine. That one was easy, nobody's horrified. Okay, let's look at the managed adult, the professional young woman. Uh, her regime is that she has oral contraceptives as a life choice, but she's also on some sort of seroton reuptake inhibitors just to cope with low-level anxiety in her workplace. So she's already taking two drugs. She's going to take oral contraceptives, let's face it, through most of her reproductive life. And the relationship with anti-anxiety medication is a complicated one in terms of how long people use it, how long they potentially taper when they want to come off it. But she's already taking two drugs which could be framed as being lifestyle medications, which are delivering autonomy to an individual, allowing her to live the life that she has chosen, but again, it comes with an ecological rucksack. Those synthetic estrogens are going to get into the water course. Those synthetic estrogens are going to have an effect on the creatures, the invertebrates, the fish within the water courses. They are endocrine disruptors. It is going to have an environmental factor. Does that mean we shouldn't do it? No, but it probably makes you think that somebody should have thought about that first and put in place a mechanism to prevent that from happening. But of course, they didn't. But it's a very clear example of how something which is good and has tremendous advantages for society can uninvert inadvertently have a negative impact on the environment, which people did not consider. And again, I'll show you later just how much of the anti-anxiety medications you can detect in our rivers. Yes, it's it's all there. Yeah? It's going through, you know, our sort of like water systems, as we can see it. So, okay. Still, nobody's particularly upset this is going well. Okay. The middle-aged professional, I tried to pick somebody who looked very stern and who might shout at you if you missed a deadline, if that worked quite well. So obviously, he's um high pressure job, um, but probably his lifestyle's become a little bit more sedentary than it used to be when he was younger. He's got some cardiovascular issues, so he's on statins and he's going to be on them for a very long time. He suffers back pain because of the nature of his job, so he's taking some general sort of like painkillers. Um, but if you think about it, he's moderating a risk factor for a disease, and he's dealing with symptoms of his lifestyle. Yes. So again, quite a lot of this is moderating his lifestyle. And you know, statins are a tremendous success story, but for every pill of raw material in a statin, there's a hundredfold chemical legacy of materials which it took to make that one single pill. You know, the pill doesn't just magic its way out, it has its own supply chain, it has its own waste cycle. And it might not be huge, but when there are several hundred million prescriptions, then suddenly it becomes very large indeed. Okay, keep on going. Here we have our post-menopausal trailblazer not going down without a fight. Um, she's on hormone replacement therapy, so the same issues, really, as with oral contraception. You know, we have more oestrogenic compounds going into the environment, but she's also taking high dose vitamin D because somebody's told her that that would be very good for preserving mineral bone density and preventing fractures as she gets old. And she's potentially also taking some biphosphos phosphates, which again are drug which are effective at sort of staving off brone bitleness as you grow older. Um, this is interesting because, again, aspects of this are lifestyle to a certain extent. They are moderating the experience, is softening the symptoms of menopause, making life easier. Um, and some of the things she's doing are to offset a disease that she hasn't had yet. And you could argue that's a very good thing. But bisphosphates are quite non-degradable if they get into the environment. And has anybody really thought about that? No. So, again, all of these decisions, these archetypes are making, are entirely sensible at an individual level, but they all have an impact on the environment to some extent. And I just want you to think this is the archetype, but do the multiplication. Multiply the archetype by the number of people who will also be in the sector to have the film. Now, this is my favorite archetype, so I'm not going to upset you yet. I when I was putting this together, I decided he was called Arthur. Um, so he is 78. He is a good patient, he has multi morbidities, he has heart disease, he has diabetes, he has COPD, he's probably on 10 medications, he's on rapamil for his blood pressure, he's on metaphorbine for his diabetes, he's on omopresol for as a protein pump inhibitor because of the good, the acid reflux which is associated with taking the other drugs. But he also likes to live a bit, so in the evening he has rum, um, and that improves his his his his sort of like quality of life. And um somebody told him it'd be a good idea to take St. John's wart because that'd be good for any depressive symptoms he has. And of course, what does this mean? Well, he's he's a classic polypharmacy individual. He has all of these drugs, each of them are targeting an or an organ system, a disease, which is organ-based. Few of them have really been sensitively titrated to the other organs to see how they work in in concert. And St. John's wort, of course, is going to have significant impact on the efficacy of his heart meds, and that's one of those things people don't tell you. But the reason I put him here is he's almost a walking sort of environmental hotspot of pharmacological excretion in the environment, yes? Because what goes in to Arthur at some point will come out of Arthur, and he has a lot going on. So let's break this down. I thought this is Arthur's pillbox, and anybody who you know has relatives of a certain age will be familiar with this sort of scenario. It's a it's it's how the modern life is. But let's just break this down into a few things. Prescriptions are going up. We start off and we are using medicines as rescue. And we have transitioned from medicines for rescue to medicines for chronic long-term maintenance. Yeah? So we are offsetting the progression of disease. So it's still odd that healthy years are going in the wrong direction at the population level. You have to make these drugs. The central panel, it's just a schematic, but between 1996 and about 2021, the CO2 signature of pharmaceuticals increased by about 70%. So it comes with a CO2 signature which nobody really talks about, and it's going in the wrong direction compared to other industries. And then we have our little ecological uh rucksack, and yes, I have picked on the GLP agonists because they're quite kind of complicated. They take lots of raw materials, they use quite a lot of very, very aggressive solvents to manufacture, and nobody has that discussion about them. They just see the benefits of the weight loss. Um, and the weight loss that's a talk in its own right, I think, how persistent the weight lost is from those agonists. So this has a whole host of environmental signatures, and that's before you even get to the fact that you know it's an industry which is absolutely dominated with single-use plastics all the way through it. And I've just made a list here, packaging all those blister packs, quite difficult to recycle, all the plastic pots you have, all of the GLP injection pens. Um, and then I thought I should give myself a hard time because I'm a research scientist with a lab. And if I was to total the amount of single-use plastics I've used in my experimental life, it would be absolutely astronomical. So I can't stand here and be virtuous. I probably have the worst plastic signature of anybody in this room. Okay, so let's return to this exposome concept. Here's the individual, he's taken his drug, and that drug gets taken into the body, it's absorbed, it distributes, sometimes it's storage, sometimes it's metabolized, but ultimately it's excreted. And this is a really key issue because how you excrete drugs varies, and how you metabolize them varies by age. So let's think of poor Arthur. The thing with Arthur is that he's already lost 30 to 40 percent of his hepatic liver mass. Um, his capacity to detoxify chemicals has fallen. That's an age-related phenomenon. Um, his kidneys don't work as well as they used to work. So when Arthur takes the drug, a significant proportion of that drug comes out of Arthur unmodified. The bioactive drug goes in, and a large proportion of that bioactive drug comes back out with the metabolites because simply of his age. And it's one of those phenomena. So when I said He's a hotspot. He is a hotspot. He is quite leaky in terms of parent compounds entering the environment. And we kind of know the route, don't we? I really struggled with this because I was desperate to actually have a toilet in aggression talk, but I've just gone for the sign. This is, you know, this is our route of exposure, you know. Urin feces, water course, two waste water treatment sites. Those wastewater treatment sites sometimes overflow all the things and it goes into our rivers. So this is the point at which those drugs which have escaped the system can enter the environment. And these are the stories I think you hear the whole time in the media. And they are really fascinating stories. So look, as a scientific area, if anybody wanted to do science and take up a science career, studying toxic chemicals in water at the present moment in time is quite hot. So here we have the number of publications which have been published. You can see if you look at the sort of there, it says we have pharmaceuticals, it's in blue, hardly anything, and from about sort of 2000 it goes up. Everybody's suddenly interested in measuring pharmaceuticals in water. When I say pharmaceuticals, they often call them emerging chemicals of concern. And very often the only thing people focus on is the cocaine and the illicit drugs. Yeah, they forget about the medications. This is a piece of data from the Norman Network, which sounds kind of insane, but the Norman Network is this network of research labs across Europe which measures water and looks at emerging chemicals of concern. And what this is telling you is how many emerging chemicals of concern are regularly quantified in Europe, in these areas in the rivers, the wastewater, the groundwater, the seawater, the lakes, and the reservoirs. And you'll see that there are quite a large number of drugs which are appearing in chemicals which are appearing in our water course. And this allows me to pivot to just one and to bring it home a bit. This is very busy. See that graph here with all these lines going up and down? This is a whole list of chemicals. Some of them are pesticides, some of them are PFAS, some of them are drugs, some of them are drug metabolites, some of them are cocaine, some of them are ketamine. You'll be quite surprised how much ketamine is floating around. But the one I wanted to highlight, right just at the top here in green, is we have imid chloroprid. It's uh very high and it's just about everywhere. And this study was done by my colleague Leon Barron and his he had an excellent student called Melanie Egli. And um during COVID or around lockdown period, she went around and she's collected samples from all that from the Thames, hundreds of them to make these measurements. Um and the reason that this compound is interesting is that it's um it's a nicotinoid insecticide. It's incredibly toxic. In fact, if you then try to rank it by toxicity, it's the most potentially hazardous chemical within the water that we have. But where is it coming from? Hate me now. It's coming from your pets. It's coming from your flea treatments, the spotting on the collars at the back of the neck, fitamil and this compound are parasecticides. And unfortunately, once you put them on your cat, and they're very popular because they kill all the fleas within 24 hours, but they kill all the other invertebrates which are exposed to it at the same time. And if your dog then rushes off and jumps into the water, it's then in the water, or if you don't dispose of your cat litter in an appropriate fashion, you're then adding that chemical compound into the environment. So the pets are actually a vector, and so actually they've become an archetype because the way we treat our pets now means that they also have a polypharmacy. You know, they have their pesticides, get rid of their fleas, they have joint supplements, they have antibiotics, they have antidepressants, and it's not terribly well regulated. And people, you know, people don't think about where their animals are going, cats in particular, and what they're doing. So I give you a bit more information on that. This is another study just looking at the two major classes here. This is a study, it was done in London. They took water upriver at the inlet going into a waste water treatment set site, at the outlet of the waste treatment site, and downstream. The idea being that it would collect and concentrate at the waste transfer site, and then it would sort of then be released. And it's in all of the samples, um, not the upstream ones. It has to really come into contact with the waste transfer sample. So they are being concentrated. But this has actually caused quite a lot of alarm, and the government is beginning to ask questions about whether we should be regulating these parasecticides at the present moment in time. Um, there are many of these things, and I just put this up because it's so elegant. This is a this is a citizen study which has just been done. Um, water samples all over the country, and then chemical composition. I just thought it'd be quite nice to read off some of the chemicals we have in our water: tramadol, caffeine, uh, lidocaine, nicotine, ketamine, there's always ketamine, I don't know why it's there. Um a whole mixture of anti-anxiety drugs, blood pressure drugs, analgesics, recreational drugs, they are all there in our water course. So what we take as a population is definitely reaching the environmental space. And when it arrives in the environmental space, it enters the food chain. So it gets taken up into the invertebrates. This is an older study again, looking at these chemicals. These are invertebrates which they've looked at the loading of these chemical compounds into them. I've got a horrible graph here, but all you need to know is look, those are different sort of areas. That's a list of chemicals, that's how frequently they were measured. And again, we have some pesticides, we have ketamine, we have cocaine in every one of those samples. Um, and then if we go down here again, reset, we have sort of like again, trimodol, a whole host of common pharmaceutical compounds. And I've just highlighted a few of them on here. Probadol, beta blocker, for example, fanuron, that's a sort of pesticide, lidocaine, anagesic, for example. And uh what's in the bug is also in the water, so that's not a surprise. But that could just be the United Kingdom, couldn't it? Because the United Kingdom, we've been told we are we're sort of like the sinners of the world, uh, but it's not. This is the global analysis. Um, so this is 250 sites globally, 1,000 samples, measuring 61 of the most common pharmaceutical sort of like compounds. Um, and you can see they are absolutely everywhere across every continent on the planet, and the United Kingdom sits somewhere in the top between the 90th and the 80th percentile. So the chemicals that we've released, including our pharmaceuticals, are in the biosphere, they are everywhere. Should we be worried? I immediately say no, and I say that because I'm a toxicologist, which means I often go, just because something's there doesn't mean it's at a concentration that's going to do any harm. That's the next step of this question. But there is one area of concern that does make me worry about these drugs in the environment, and that's when antibiotics and unregulated antibiotic use make it into the environmental space. Now, over here we just have a list of mutations, just you don't need to know the numbers. These are all mutations that can happen in your sort of microbe, which will confer resistance against the standard antibiotics. And the antibiotics usually either stop the drug from being taken up or they promote it from being degraded or they change the nature of the cell membrane. But the chemicals in the water and antibiotics within the water create a perfect environment for the selection of those mutations in those genes, and those bacteria are geniuses of exchanging virulence factors. So currently, this is a battle we will not win. Antibiotics are in a dangerous place because the bacteria will win this battle. They reproduce faster than we can innovate new products, and we allow chemicals and antibiotic chemicals into the environment. And we do it in a really cack-handed fashion sometimes. Um of the hotspots for antibiotic release is the um are the waste water from hospitals. So if you go to hospitals and look at the wastewater, they're a very high concentration of antibiotic materials and other pharma compounds, which are known to promote it. And of course, the other individuals, the other places where it's high, these are actually antibiotic manufacturing plants. There's one in India, one in China. The effluent concentrations are 31 MGs per litre, 20 megs per litre. Those are actually farm, those are the levels you would want to achieve for them to be doing their job in the human body, yes? And this is a huge issue, because it means effectively you could do everything right in the United Kingdom, but you could still have a massive destruction of antibiotic resistance across the planet because other countries aren't following the same rules, and we know how quickly infectious agents can spread transcontinentally. So these are huge issues, and if for no other reason, this is why we should be focusing on how we use drugs and how drugs reach the environmental space, because otherwise, that environment, that epidemiological transition we saw from infectious disease to non-communicable disease is gonna flip back because living without antibiotics is not going to be a pleasant experience. Now, what can we do? Say something positive. They always tell me to say something positive. There are the green chemistry principles, pharma is signed up to trying to make new generations of drugs better, more sustainably, with less solvents, with less material, and less waste. This is a very, very good thing, and they should be applauded for doing it. If they do it everywhere. And there are examples where they will follow the rules in one place, but maybe not in another jurisdiction. And this is another key question. Who pays for this pollution? It's a really interesting question. So in America, they have regulations based on the concentrations of specific compounds in water. And if you go over it, then you get hit with massive fines. There is legislation. In the European Union, they've just brought in a new directive, which will be tightened in about 10, 15 years' time. So they're moving forward to make sure that there are regulations to remove chemicals from the water and to make sure that people who produce the chemicals are responsible for doing that. And in the United Kingdom, we're thinking about whether we should do anything about the regulations we had, which we took from the EU previously. So we're lagging behind a little bit to be precise. Now, all of that, I think, might make you wonder why I'm still quite positive, and I'm sorry about the cat, because it's very cute. But I think this is really kind of important. It's one of the things which is getting lost in the debate. The reason that life expectancy has fallen in the United Kingdom, the reason that years of healthy life have declined is because of poverty. It's economic. As the wealth gradient has widened, people have struggled more, and those individuals have struggled. If you disaggregate those statistics by the top 10% to the bottom of 10%, then you begin to see where the actual statistics are coming from. So when we think about all of these things, I still think we have to think about where people live and how people live. And the question for me isn't um isn't about criticizing pharma. It's about rebalancing the discussion. We have had a hundred years where remarkable progress has been made to the benefit of mankind. Not everywhere. There's still an element that we get to live longer in the West because people are producing drugs for us in countries which don't have access to those drugs. That's a bit of an issue. But the next hundred years needs to be how we achieve this without crossing planetary boundaries and damaging the planet. And I think we can do that, and I think it would be a tremendous growth area for science and the economy as a whole if people would embrace this as a concept. And with that, that's about as positive as I ever get. These words are absolutely true. Um, and I hope that you have a wonderful evening. Thank you.