Gareth Mitchell:               Hello, everyone. I'm Gareth Mitchell, and in this edition, we are hearing about supersonic and hypersonic flight, but we're slowing down a bit too to discuss the worrying environmental effects of the treatments we spray onto our pets and get them to swallow.

Andrew Prentis:                What we're talking about here is worm pills, flea treatments. It's the kind of parasite treatments that many pet owners are picking up from the vets, or indeed in many cases from pet shops and pharmacies now. And the reality is these medications, these chemicals are pesticides.

Gareth Mitchell:               And they're finding their way into our rivers, ponds, and lakes where they're causing real harm. Also in the podcast: tackling tuberculosis, through mathematical modeling.

Gareth Mitchell:               All right, well, as we always do, we're going to jump in with some news around the College. And today we have a double bill of Imperial news from none other than Conrad Duncan. Thanks for being here, Conrad. And one of the stories you've been involved with has been really hitting the headlines. In fact, both these ones have. But let's start with the study into DMT. It's a compound and it's a psychedelic compound, isn't it? And this is research about how it affects people's brains in brain scanners. What a story. So what do we need to know?

Conrad Duncan:                Yeah, so this is a study that's been published in PNAS from Imperial’s Center of Psychedelic Research. So scientists were looking at, as you say, DMT, which is a powerful psychedelic known to alter conscious experience for its effect on brain activity. So DMT can produce very kind of intense and immersive altered states of consciousness, the feeling of maybe like visiting an alternative reality or seeing things that aren't real, what we think of as hallucinations. And it's the major psychoactive compound in ayahuasca, which is a psychedelic brew that it's used in ceremonies in Central and South America.

                                             Now, what was going on this study is that scientists were basically looking at tracking brain activity before, during and after this experience in kind of better detail than ever before. And what they found is that during this experience, there was increased connectivity across the brain with changes that were most prominent in areas linked to what we think as higher level function, so imagination. So Dr Chris Timmermann, who is the lead for this study, he says that human brains model an unusually large amount of the world. So for example, when you have an optical illusion, what our brain is doing is it's basically filling in the blanks of what we would expect to see based on information we already have, rather than showing us what we're actually seeing. And under DMT activities in these areas and systems of the brain become highly dysregulated. And this is what leads to the trip experience as we know it.

Gareth Mitchell:               Obviously, this research is just fascinating in its own right, fascinating insight into what's going on in the brain under these altered states. But do the researchers see a further endpoint to this? Is there a clinical endpoint, for instance, to understanding these interactions?

Conrad Duncan:                Yeah, so studying DMT this way when the brain is in this extreme state of altered consciousness is useful for us understanding how brain activity affects consciousness in general, but it's also important to understand how DMT works and how it has the effects that it does on the brain because DMT is one of the various psychedelics that has potential as a treatment for depression and other mental illnesses, as has previously been looked at with psilocybin, the active compound in magic mushrooms.

Gareth Mitchell:               All right, Conrad, while I have you, let's talk about another compound that gets a lot of attention. This has also been a big news story Imperial's been involved with and its caffeine and what it has to do with the likes of obesity and the type two diabetes.

Conrad Duncan:                Yes, this is research from our school of public health, and they've basically been looking at how high blood caffeine levels may reduce body weight and the risk of type two diabetes. Now, there's been lots and lots of research over the years about caffeine and its impact on health. What's interesting about this study is they use a technique called mendelian randomization, and this basically uses genetic variants as a tool to investigate the relationship between a trait and an outcome. So in this case, they're looking at two genes that are associated with the speed of caffeine metabolism in the body.

                                             And essentially what they found is that having a high blood caffeine level reduces body weight and the risk of type two diabetes. Now, what mendelian randomization is able to do is it can show causal relationships, which observational studies can't show in the same way. Observational studies are great at showing a correlation, but it's hard to disentangle all the other factors that are going on in person's life that may be impacting their health and to separate caffeine from those issues. So Dr Dipender Gill, who is senior author the study notes that further research is needed before individuals should use these results to guide their dietary preferences. But it does suggest that the findings show that there may be worth in exploring the potential use of caffeine-free carbonated drinks in lowering the risk of obesity and type two diabetes in patients.

Gareth Mitchell:               All right, so there you are. That's caffeine and DMT all in the same new section and busy time for you as well. So thanks for taking time to talk to us, that Conrad Duncan. All right. Now, when I was younger, I wanted to be either a Concord pilot or a space explorer. So more recently when I found out that Imperial had a podcast all about supersonic and hypersonic travel hosted by an astronaut, well, I hit that download button very, very quickly and I humbly suggest you do too. I've been listening to an edition of the Zero Pressure podcast from Imperial College and Saab. It's billed as a relaxed conversation with those on the cutting edge of science and technology hosted by Britain's first astronaut, Helen Sharman. Well, having consumed the super and hypersonic edition, I've been working my way through the back catalog as well, checking out episodes on 5G, the hydrogen revolution and quantum computing. But to give you a taster, let's go supersonic. Here's Helen in conversation with Conrad Banks of the aerospace division at Rolls-Royce PLC.

Conrad Banks:                   I actually saw the last Concord aircraft landing in Bristol in 2003. I remember it vividly. There was a very unfortunate incident in Paris that people remember the crash of Concord. And very sadly, a lot of people lost their lives. It was a freak accident, but the industry lost confidence and it wasn't a viable concern going forwards. So British Airways, Air France were losing money, the aircraft was declined, and services stopped. Now, at the very end, it was very popular, but Concord never recovered from that crash in Paris all those years ago. If it was still flying today, I think there'd be lots of question marks about the environmental concerns and the drive for sustainability, and that's going to be a very important factor when we talk about the future of high speed.

Helen Sharman:                So what do we need to overcome then if we're going to have supersonic travel commercially again, I think you're saying that we need it? There is a demand for it, you think again, now?

Conrad Banks:                   Of course, there's a demand. People want to travel at speed. It drives huge benefits to society, but equally, our planet is precious, and we can't risk climate change and other environmental issues just for the convenience of traveling across the Atlantic and the Pacific at two, three, four times a speed of sound. So we have to find that marriage where we can deliver a sustainable supersonic high speed future with an affordable future. So we have to introduce a lot more technologies that enable us to travel fast and deliver that huge advantage to society that high speed bring. There is a demand. We know there's a demand, but we cannot do it in such a way that we risk the sustainability and the environmental concerns of net-zero.

Helen Sharman:                So we're thinking about emissions. Are we in particular for sustainability? So how do we make sure that those emissions are going to be suitably low for supersonic travel?

Conrad Banks:                   It's not just about the emissions being low, it's about the net-zero aspect of that. The higher and the faster you fly, you actually burn more fuel per mile. It's less efficient, it's far more efficient to fly people in A350 than fly people in a later supersonic aircraft when they are developed. So they are going to be less efficient. And the other challenge of going supersonically is you need even more power density. So in Rolls-Royce, we are doing a lot of work on electric propulsion, hybrid electric propulsion. We've just tested a gas turbine that runs on hydrogen, but none of those are suitable for long-distance, high-speed flight because of the energy and the power density that you need. So we have to face the reality that we need some form of hydrocarbon fuel and it will emit CO2, but that CO2 has to be part of a net-zero cycle.

                                             So it is absolutely essential if we are going to have a future in high speed commercial flight that sustainable aviation fuels, SAF or better still synthetic aviation fuel that synthesize from water from the air powered fully by renewables. And in Rolls-Royce, we are looking at small modular reactors, for example, that are going to provide that carbon-free power, but solar and wind sustainable manufacture of fuel. So that the carbon is absorbed from the air and then when it is flown at high speed, it is put back, it's net-zero. That's the only way this is going to work. If we dig up a gram of fossil fuel to power supersonics and future high mach, we are failing society. It's just not acceptable.

Helen Sharman:                Now, quickly before you go, Conrad, how many years do you think it's going to be before we actually see a fully operational supersonic passenger aircraft?

Conrad Banks:                   If you involve business jets, we say passengers within the next 12 years.

Helen Sharman:                Gosh, that's exciting. 12 years, mid-30s.

Conrad Banks:                   Yeah.

Helen Sharman:                Wow. Exciting.

Conrad Banks:                   And that's passenger paying first flights. Well, beforehand.

Gareth Mitchell:               Conrad Banks, Chief Engineer, Defense future programs at Rolls-Royce, talking there to Helen Sharman on the excellent Zero Pressure podcast. And like many other titles from Imperial, you can find it on our shiny new podcast directory, access it via the Be inspired pages on the college website. Well, now let's talk about parasite treatments for our pets. Now they help get rid of fleas or ticks, but research says that the chemicals are getting into rivers, lakes, and ponds and threatening aquatic wildlife. There's a load of detail on the problem in a new briefing note from the Grantham Institute. One of the authors is Rhys Preston-Allen, and he's pulled together a panel of experts to discuss the issue.

Rhys Preston-Al...:           Altogether, there are around 25 million cats and dogs in the UK. These animals are routinely dosed with parasiticide drugs that can protect against parasites like fleas, ticks, lice, and worms. But how much do we know about the impacts of parasiticide on the natural world? In our Grantham Institute briefing paper, we explore the potential hidden impact of these chemicals within our waterways. Could the cost of allowing these chemicals into the environment outweigh the benefits to our pets? Today, we are joined by a bounty of environmental researchers and students based at Imperial College, Dr Leon Barron and Hamish Duncalf-Youngson, alongside our Veterinary Activist in Chief, Dr Andrew Prentis. So Andrew, as our resident vet, would you be able to define what a pet parasiticide is for us and perhaps give us an idea of how they might be getting into world ecosystems?

Andrew Prentis:                Right. Pet parasiticide is a bit of a mouthful. In lay terms, what we're talking about here is worm pills, flea treatments. It's the kind of parasite treatments that many pet owners are picking up from the vets or indeed in many cases from pet shops and pharmacies now. And the reality is these medications, these chemicals are pesticides. And so, we are using significant quantities of pesticides on our pets, and we are now increasingly concerned that some of these products are getting out into the environment. And we know that because there's already been documented work showing that some of these products are out in the waterways. And this project is largely about trying to find out how extensive that is. So the question is how might these products get out into the environment for the topical preparation?

                                             So the things which are generally referred to as spot on. So these would be liquids drops you put perhaps on the back of your dog or cat's neck and they diffuse out into the coat and then into your pet in order to kill the parasites. Well, they don't instantly absorb. If your dog, for example, then went for a swim in a river, then there's a significant possibility that some of this product will wash off into the river. But equally, if you were to decide to wash your dog or even wash the bedding that your dog had been sleeping on or even decide to wash your hands after you put the product on because you've got a couple of drops of the liquid on your hand. In each of those situations, some of that chemical product is going to go down the drain and it will in all likelihood go straight through the wastewater treatment works and end up in the rivers.

                                             Now the individual quantity from the individual animal is tiny with an excess of 20 million pets in the UK, a large proportion of whom are receiving treatment frequently, you have got potential for significant wash off. Now, the other type of medications are the ones that are given in tablet form, it's largely unknown at this stage. And we are now looking for those products because even if they're taken them by mouth, the root of excretion, are they going to come out in the poop? Are they going to come out of the urine? Are they going to... Somewhere that parasiticide may be ending up in a waterway, maybe up ending up in landfill? There are multiple different routes for which these products could get to the environment which are not immediately obvious as you apply with all good intentions, something to control parasites on your pets.

Rhys Preston-Al...:           Through the years, there appears to be a fairly consistent cycle of chemicals being introduced as biocides and then banned. So Andrew, what's the current state of play for the chemicals used in pet parasiticide?

Andrew Prentis:                One of the difficulties is that for medicines used on companion animals, there is relatively low requirement for assessment of environmental risk. There has always been an assumption in the past that these products did not get into the environment because they were used on pets and therefore the bar was separately low. Now, that knowledge base is changing, we know they are out there. So it's very important of this stage for us to be able to gather more information so that we can actually start to make policy based on fact rather than on assumption.

Rhys Preston-Al...:           So Hamish, where do we find evidence of the chemicals used in parasiticide in UK waterways?

Hamish Duncalf-...:          I'll start by saying that these chemicals extremely pervasive in general. A paper that came out last year found 98% of rivers sampled had the chemical fipronil on and 66% had the chemical imidacloprid from it. But increasingly what we're finding is that the spatial pattern is that there's a lot more of these chemicals found in greater abundance in urban areas as opposed to rural areas. What's more with increasing populations, this is a problem that has the potential to be exacerbated.

Rhys Preston-Al...:           And Leon elaborating on that, when we're detecting these chemicals, are they at concentrations of concern?

Leon Barron:                     To take an example, imidacloprid, which is one of our pet parasiticide essentially is very, very toxic at very, very low concentrations. So the current way of assessing whether a substance has any risk in the environment is to find the most sensitive species to that chemical and understand what the lowest concentration is before that has some form of effect on that most sensitive species. So sort of like the worst case scenario, and in this case here we have a no effect concentration for imidacloprid of a very, very low 13 nanograms per liter is predicted no effect concentration for imidacloprid. And that value is very, very low, but very much so in the range of what we measure in the environment, the concentrations in the environment are high enough to pose some form of risk.

Gareth Mitchell:               That's Leon Barron and some of his co-authors on that Grantham Institute briefing paper, speaking to Rhys Preston-Allen. Right now, this Friday, if you're listening to this, on the day that we published sees World Tuberculosis Day. That's Friday the 24th of March. So to mark it, Natasha Khaleeq of the Institute of Infection has been speaking to Nimalan Arinaminpathy, a professor in mathematical epidemiology in the faculty of medicine. He researches human TB transmission and control, and he works with governments on national TB control programs. He's working mainly with India, which has the world's largest burden of TB, and Kenya, where HIV is a significant driver of tuberculosis. And dealing with TB is a challenge, not least of all because it tends to affect countries with limited resources to deal with epidemics, but computer modeling can help health authorities allocate their scarce resources and set priorities. The conversation begins in India.

Professor Nimal...:           India's TB program is probably the largest in the world because their TB epidemic unfortunately is the largest in the world. Until recently, they were known by another name, the revised National Tuberculosis Control Program. But there's been a step change in the amount of ambition. So they're not talking any more about TB control, they're talking now about TB elimination. And their mission is really to find and treat TB as quickly as possible. In recent years, they've been doing so much more aggressively and also reaching out to other types of interventions like prevention, protecting patients from catastrophic costs and so on. And so, it's a very exciting time to be working with programs like that where you have this recent pretty large expansion in controlled efforts. But India is a huge country, vast and diverse with many different states with many different challenges in terms of their healthcare system, but also their TB burden.

                                             And so, the response in different states really has to be tailored to their local needs. And so, one of the ways in which I've been working with the National Tuberculosis Elimination Program has been to look at each state, state by state and to look at the evidence there is for their TB burden to model scenarios for different control strategies in the coming few years, and to address what levels of coverage India would need to achieve in order to meet their ambitious goals for TB elimination.

Natasha Khaleeq:             So you're traveling to India for World TB Day. What work will we be carrying out while you're there?

Professor Nimal...:           There are a host of different projects that we have in progress. I'm working with the TB program at the national level. Now, what we've recently developed is a user-friendly modeling tool, and the idea is that modeling analysis should not be something that's just done by modelers at Imperial, but rather these models should also be accessible to the people actually doing the work in India in terms of delivering the program. And so, we try to develop this resource where state level planners, health planners, for example, could easily run different modeling scenarios for their specific states and to see what the impacts of different interventions might be. Another important task for the program is also they've recently conducted a huge prevalence survey in the country, and this is where you go out proactively into the community to try and find TB and to try and get a better estimate of how much of the disease is actually there in the community. And so, I've been working with the program also to help them analyse that data to get a better sense of how much TB there is in the country as a whole.

Natasha Khaleeq:             What challenges does antimicrobial resistance pose to the future of tuberculosis research?

Professor Nimal...:           Drug resistance in tuberculosis is definitely a really important and pressing problem. In India where I do a lot of my work at the country level, it accounts for only maybe around three to 5% of the incident TB that happens every year. But that's not to say that it's a small problem because if you look at the within country level, what we call the subnational level, there's certain areas in India that really suffer a high burden of drug resistance. So Mumbai for example, a huge megacity in India has a pretty large burden as well as certain areas in the northeast of the country. And the problem with drug resistant TB is that it is much harder to treat. The treatments are more prolonged, they have much worse side effects and all of that for poorer outcomes, and they're extremely expensive as well.

                                             And so, from a patient welfare point of view as well as from a program financing point of view, it'll become really important to bring down the burden of drug resistant TB, and that's in the case of India. But if you look at several countries in Central and Eastern Europe, for example, they have far higher rates of drug resistant TB. And so, the problem is even more urgent and even more pressing in those countries.

Natasha Khaleeq:             The theme of World TB Day is, yes, we can end TB. With this in mind, do you have a message or call to action to other researchers that you would like to share?

Professor Nimal...:           That's a great question. Yes. I mean, I think after so many years of slow declines of TB burden, and also recently with the disruptions that we've seen during COVID having set us back several years, it's very easy to feel a sense of fatigue and perhaps even a sense of despondency about whether it is possible to do anything about TB. But there are success stories and there are examples in India, in Southeast Asia, in other countries where really focused concerted action has actually brought down TB burden dramatically. And what I would say is now's not the time for fatigue is not the time for despondency is the time to really redouble our efforts and to bring the global TB response back on track.

Gareth Mitchell:               That's Nimalan Arinaminpathy speaking to Natasha Khaleeq ahead of World TB Day on March the 24th. And that brings this edition of the podcast to a close. Of course, at this point, I always like to remind you that we like to go wherever you need us, in other words, on all your favorite podcast platforms, I'm sure you know the ones we mean by now. And if you don't want to listen to the whole thing, then you can of course, listen to chapterised versions of this podcast. You can find them on our pages via the Be Inspired webpages here at Imperial College. So that'll do. For now, I'm Gareth Mitchell on behalf of me, and everybody else here on the podcast team. Thanks for listening, and goodbye.