Dr Kyle: You're absolutely right, because soups and shakes and things like that, something which is easily mixable, neutral flavour. It's going to turn everything bright green, but I don't think that's necessarily the worst thing. You know, it's it's it could work, it could work really well. And then once we're up and running, we're established, we can start hopefully working with maybe sausage manufacturers or other people and say, well look, what about replacing 30% of the meat in the sausage with this watercress?
Dr Rupy: Welcome to the Doctor's Kitchen podcast. The show about food, lifestyle, medicine and how to improve your health today. I'm Dr Rupy, your host. I'm a medical doctor, I study nutrition and I'm a firm believer in the power of food and lifestyle as medicine. Join me and my expert guests while we discuss the multiple determinants of what allows you to lead your best life.
Dr Rupy: Watercress. It is a beautiful ingredient, peppery, vibrant, grown in the UK and fantastically healthy for you. It's a vegetable from the brassica family and that includes other favourites of mine, including broccoli, cabbage, sprouts, bok choy and more. And a few studies demonstrate their ability to reduce DNA damage, which could explain the association between brassica vegetable intake and reduced cancer risk. And watercress is also known to be a good source of lutein, beta carotene, which are great for your eye health and vitamin C. But is that all? Well, on today's show, you're going to hear how Dr Kyle's experience with a young child suffering nappy rash led him to find out more about the wonderful properties of watercress and how research that has stemmed from this ever so common problem that a lot of parents can attest to, can also extend to reducing the need for antibiotics, preventing and treating certain cancers and even creating a new form of plant-based protein. Starting off by finding out about the mechanism behind nappy rash and its relationship to ammonia, Dr Kyle discovered that watercress contains urease inhibiting properties. But the rabbit hole goes a lot deeper. Dr Kyle is a GP in South Devon, as well as CEO and co-founder of Watercress Research Limited. He holds an honorary clinical associate research fellowship in theoretical medicine at the University of Exeter, and he's also on the clinical entrepreneurship fellowship program, which is how we were connected. We also have a wider conversation about the untapped potential of plants in general and how little we know about these incredible ingredients that we consume every day. And you know what, if you consider the successes of cardiac drugs like digoxin and blood thinners like aspirin that have all been discovered from plants, it stands to reason that we should be aggressively investigating these more by using different preparations, experimental methods and a sprinkle of ingenuity, which is exactly what Dr Kyle and his co-founders also did to create almost like a completely new class of plant medications that have the ability to treat everything from eczema to IBD. I think it's fascinating and super, super exciting. And I think there are lots of parallels with CBD as well that we also talk about. As always, please do us a favour. If you want to support the podcast, do so by subscribing on Apple or hit follow on Spotify. It really helps the rankings, which means we get more listens, which means we can do more podcasts, and do sign up for the newsletter at thedoctorskitchen.com where I send a weekly wellbeing trio of things to do, something to eat, a recipe, something to listen to, not always this podcast, but other things, watch or read that will brighten up your week. And for now, please enjoy my conversation with Dr Kyle. So we met through the clinical entrepreneurship program with the NHS. You've been on it for a little while now. But before that, why don't you talk us through your sort of clinical career and and and how you've how you've got to playing around with watercress so much.
Dr Kyle: So I'm, I'm a GP, so I did my medical school training in Birmingham and while I was doing that, I did an intercalation in medical sciences. So I was investigating carotid body cells for my dissertation and around their ability to sense glucose and different levels of oxygen. So I've always had an interest in sort of the underpinning biochemistry of plants and animals. Finished my training and then I started an academic foundation training at Torbay Hospital. And I think this was really one of the the key things for me because the academic training post gave me a week every three weeks to be able to do quality improvement and research and that gave me the time to to focus on other things. And the way the watercress came about was was quite interesting. So I was on a ward round doing paediatrics rotation and we saw a really poorly baby who was septic from infected nappy rash. And as I often did, I you know, I didn't know what caused nappy rash and I was interested in understanding the the biochemistry. So I went away and had a bit of a read about it and found out from urine at least, nappy rash is a chemical burn from ammonia. So you've got lots of bugs in the urine and on the skin with an enzyme called a urease enzyme that converts urea to ammonia. So nappy rash and the same rash that we see in the elderly is an alkaline chemical burn. And the professor I was working with at the time, he's a biochemist by background. So we and he was he's also a physician, an acute physician. So we had a look at whether urease inhibitors had ever been looked at and we found some evidence that they had been looked at for things like struvite kidney stones when the urine becomes alkaline, calcium phosphate comes out of solution and crystallises and makes stones, but they never were very well tolerated. So there's one licensed in the United States, there's never been one licensed in the UK, despite very good evidence that actually urease inhibition could be a novel target. So that then led me to go away in one of these academic weeks off that I had and have a look to see whether any plants had historically been seen to have urease inhibiting properties. And they had, so we had camomile, pomegranate and watercress keep popping up in the literature. So I couldn't find camomile in the shops. I could find camomile tea bags, but no fresh camomile apart from picking it on the side of the road, the big daisies that you see. Went to try and look for pomegranates and I couldn't really, well, I could find them, but they were full of seeds, they were expensive, they were seasonal. So I typed into Google watercress company and found the watercress company based in Dorchester. And that's where this kind of last five-year rollercoaster started really. So I contacted the watercress company and I said, look, I'm really interested in whether we can prove that watercress has got urease inhibitors in and you never know, it might be a potential treatment down the line as a really left field punt. But they said, yeah, we'd be happy to work with you on that. So we ended up getting a grant from Torbay Medical Research Fund, who I can't thank enough and I think there should be a lot more of these charities around, really quick turnaround, gave us some funding. I was introduced to a professor of experimental medicine, Paul Winyard at the University of Exeter, and we put together a project and over about three years with some additional funding from Torbay Medical Research Fund, we proved that watercress had urease inhibitors. So we set up watercress research back in back in August 2019. We took on some more funding and then we've really progressed from there. So now I now I share my time from being a GP partner and being someone who dabbles in watercress. And it's it's been a it's been a fantastic journey. So we've we've made a few discoveries along the way. We submitted a patent in December and it's it's going really well. I'm sure we'll chat more about the product.
Dr Rupy: That's, yeah, that's amazing. I wanted to rewind slightly there because, you know, the the fact that you found some small studies online about these individual products was is quite amazing and it it never fails to surprise me what you can find on PubMed and who actually has the time or the inclination to do these studies that examine the profiles of different products that we otherwise sort of, you know, gloss over. I mean, if you think about the history of some chemotherapy drugs, of aspirin, of cardiovascular drugs, you know, a lot of them have come from plants in the study of plants. So we should really be doing a lot more of this kind of stuff, right?
Dr Kyle: I completely agree. I mean, we've, we're just finishing off our website, so watercressresearch.com will be going live in a couple of months time and we've got a full page on the history of medicine and plants. So we've got the chemotherapy agents you talked about, paclitaxel, for example, you know, where that came from in plants. You've got digoxin from foxgloves, you've got aspirin from the willow tree, you know, you've got all sorts of other other medicines. So when you start thinking, when you take a step back and start thinking about it, you think, well, actually, this might not be such a, you know, an outrageous idea that we might be able to extract something clinically useful from plants. And there are hundreds of other common plants out there with interesting properties, which we're not looking at. And and it's not just what's in the plant, it's how you prepare the plant, how you can stress the plant, how you can grow it and cultivate it. We're starting to learn that now with watercress, we can completely change the profile of the plant and we hope the the clinical usefulness just by how we grow it, pick it, blend it, prepare it. So I I'm completely agree with you and that's why obviously I follow your follow your work greatly. I think the the phytonutrient world is is one which, you know, is obviously growing, but is absolutely the future for medicine, 100%.
Dr Rupy: Yeah. Yeah, yeah. It's a really untapped world, I think. And that's why it was so fascinating hearing about your work on watercress as a single ingredient. And like you said, there's so many different ways in which you can prepare the ingredient that we'll get into a bit later that can yield different profiles, which could have potentially a multi-variate uses. Going back to your grant, this is quite interesting for me because the whole grant process is is quite, there's a bit of a maze for a lot of people. And and I think if if more medics or scientists were actually encouraged and actually saw like a a simpler part to investigate different areas of of, you know, things that they're they're they're really intrigued by, we'd have a lot more research like yours. Can you talk us through that whole grant process and and why that was so good for you?
Dr Kyle: So we were really lucky in Torbay to have Torbay Medical Research Fund. So they're not affiliated with the, they're not part of the hospital, but they're obviously affiliated with it. So the history behind them are there were three law firms, the three big law firms in the Bay area would have people coming to them with legacies and monies to leave to various charities. And with a lot of charities, unfortunately, that money can go into running expensive offices, it can go into wages and not all the money, should we say, will go to what you think the end use should be. So these three law firms put their heads together and said, why don't we offer people an alternative where we make a charity and it's going to be for the the health and benefit of people in and around the Torbay area and they'll fund research with clear benefit. And you can go on their website and have a look at all the things that have been previously sponsored and they are absolutely fantastic. So they sit every three months. You have to do a two-page application and when the the panel sits, they they'll they'll shortlist you before you're invited to present, you'll present your work and then you'll be given lots of questions at the time during your presentation, but you get a decision within two weeks. And within a couple of weeks after that, the funds are ready. Now, I could have gone down the route of a, you know, an Innovate UK grant perhaps, or a smart grant or, um, I for I or one of these, one of these grants, but, you know, the risk to me at that point in something which has got such a small chance of of success wouldn't have been worth me doing. Plus, that sort of a grant, you really need to have experience in grant writing and and have a team and I at the time didn't have that. So these kind of these smaller pots of money in charities where you can very quickly turn something round as a proof of concept was absolutely invaluable to me and I wouldn't have been able to get where I am now without those pots of money. And I completely hear what you're saying. As clinicians, our time is limited anyway. And we often don't have all the answers and I think that's the difficulty with a lot of the grant application processes at the minute, you know, if you're asked about, well, you know, what's the market and what's this, we're not really trained to know about that. We've got an idea and we know the clinical side of things, but asking us, you know, what could projections be and what could other markets be? I think we often find it difficult. So for these proof of concept funds, charities like that and and and small pots of funds which are easy, relatively easily accessible, I I think we I'd love to see more of them popping up just for the proof of concept work.
Dr Rupy: Yeah, definitely. I mean, I've just literally done my Innovate UK grant application a couple of months ago and it is a massive slog. It's like three months of pure work. You've got to get everything in order. You've got to do, like you said, projections and financials and as a clinician, you know, I've been, you know, doing a bit of business now for the last couple of years, but still it was a lot of work, a lot of new learning to do. And like you said, the whole process of bid writing is an art in itself, which is why a lot of people use bid writers, which we didn't do. So, you know, fingers crossed, we'll we'll see what what happens with the decision. Good luck. Yeah, cheers. And it's sort of they're also very competitive as well. You get thousands of people writing for these because they're they're big pots of money and and you know, rightly so that they're they're super competitive. So, so you're at this point where you've got this grant, amazing pot of money with charitable foundation that makes the decision super quickly, which sounds like a dream come true. And you meet up with this professor of experimental medicine. What is, I don't think people really understand what the process of research is like. So if you've got this idea looking at some preliminary research about watercress and some properties being urease inhibitors that might be useful in nappy rash, what what's the process thereafter?
Dr Kyle: Well, to be honest, there isn't one. And very much, you know, my last five years have been a bit like a pinball machine bouncing from one place to the other, you know, two steps forward, one back and 10 to the side. So there wasn't really a process. We kind of had the end goal where we thought, you know, what we wanted to get to at the end of the day was can we get a liquid or a powder or a whatever form it's going to take with urease inhibitors in and then can we try it on nappy rash and see if it works. But we didn't know how we're going to get from this stage to that stage. And Paul who I worked with, he didn't really know either. But I don't think we still know really, but um, but I mean, I think what what we knew is we had to do things in stages. So although you might not know how you're getting to the end, it's always fairly clear what your next step needs to be. So, um, we we realised that what we need to do is we need to figure out how we get these urease inhibitors out of watercress. And we knew they were there because what we did is we we spun up watercress and then we took the sort of tea from it and we put it through a machine which basically separates all the molecules from water loving to water hating, so hydrophobic to hydrophilic. And we took various points along that path and we tested them. And of course, some of the fractions were popping up saying these inhibit urease really well, these other fractions don't. So we thought, well, they're definitely in there, but that's not going to be a commercially viable thing to do because it's a really complicated and expensive way needing university equipment to get them out. So as all good sort of scientists do, we thought, well, let's just blend it up and heat it and see what happens and see just because we didn't know. So we we thought, you know, we we tried everything at that point. So we thought, well, let's just blend it up and then heat it. And this is where we had a bit of a eureka moment because the watercress after you after we blended it up, as soon as it started to steam, it curdled. And we thought, well, we've just wrecked a batch of watercress because it's curdled and no one's going to want to eat anything that's all curdled. And then we thought, well, hang on a second, when you're making cheese, the curds are the protein. So we effectively did a bit of cheese making. We poured this hot mixture through a cloth and then we were left with what looked like a green putty. We sent that off for analysis and actually it came back to be a fantastic novel plant protein with really high essential amino acids. So we were scratching our heads thinking, well, you know, we've gone completely the other direction. We set out looking for urease inhibitors and now we've got a protein, which is great because we've got a byproduct. We then had the liquid that's that had come through as a kind of brown murky liquid. And when we tested that for urease inhibiting activity, it was fantastic. So by the sheer fluke of of watercress curdling, that's how we figured out how we were going to get these urease inhibitors out. And we now know that watercress curdles because half its calorific value is protein, which is really high. So that's about the same as a rib eye steak. Now, obviously, the steak's got a lot more calories in it. But of the calories available, half are protein. So effectively, what we're doing is just coagulating out and denaturing protein in the same way as when you boil an egg, the albumin goes from that snotty, colourless consistency and it binds together and it and it coagulates and goes white. So we got quite excited by that. And at that point, we we took on some private funding from some businessmen in Exeter who were involved in who had businesses before and one of them's in food and drink. And that's at that point, that's what we needed. So we we recognised that we had something that we could kind of see a a production process for, but again, we didn't know the first thing about running a business. So we decided at that point, we need to get people in who know how to do accounts, who would know how to do a slide deck, who would know things like that. So that's what we did. So we were quite careful in who we brought in. We brought in four guys and and they've been great. So they put in some funding and they've really helped us to to develop this business. And we've so where we are now is we've got the process which we've submitted a patent for to make this liquid urease inhibiting sort of solution and we've got a way of making this powdered watercress protein, which is sky high in amino acids and fibres and things like that. And we've we've had some good data back recently which shows if we put our watercress extract in to a fake urine with proteus in it, so proteus is the bug which most commonly causes nappy rash and and and water infections, it completely eliminates the ammonia production. So we're quite confident that actually we are going to be able to stop nappy rash and we are close to to reaching an agreement with a very big continence care provider for a range of nappies and continence wipes and creams and things like that. So that's going to be our first step. And so it looks like we might well have the future of nappy rash all wrapped up, Rupy, which I'm delighted about. That's amazing. I just want to go back to this process, right? Because I've got this image in my head of you literally using something like a Vitamix to blend up watercress, put it in a big vat over heat and then literally just heating it up at different temperatures and seeing what happens. Was that?
Dr Kyle: It's exactly right. Yeah, it was done it was done in my kitchen. So there was absolutely nothing at all scientific about what we did. And the first lesson I learned was put a lid on the pan because obviously put the blender on and everything splattered everywhere. So, so you know, we learn as we go. So, you know, the kitchen has been destroyed by watercress on many occasions, but you're absolutely right. We we weren't trying to we weren't using scientific methods a because we couldn't afford to, but b, you know, you don't need to pay a lab to blend something up, we can do it at home. So yeah, we did. We we blended things up. And what was interesting about the blending phase, so you take all the watercress, you blend it up, is as any good scientist would do, maybe not good ones, but it's what we did, is we just kept tasting it at different intervals. So we were obviously used to eating watercress when we were preparing it and we thought, well, that's peppery. We then realised that when we tasted it, we blended it up and we do something else like clean the kitchen or whatever else. And then we taste it again and it was a lot more peppery. We thought, well, that's that's interesting. So when we started looking at the literature, we realised that so watercress is part of a group of plants called the brassicas. So brassicas have got things like watercress, mustard seed, wasabi, broccoli and sprouts. So the pepperiness is a plant defence mechanism. So in the brassica family, you've got a group of molecules called glucosinolates. When you blend up the plant or let's say chew it, then they get acted on by an enzyme called myrosinase and the myrosinase creates isothiocyanates and each of the members of the brassica family predominantly produce a different isothiocyanate. So watercress makes phenylethyl isothiocyanate. Mustard seed makes benzyl isothiocyanate, wasabi makes allyl isothiocyanate. And what's really interesting is they're all being looked at for their various roles in inflammation and the epigenetic regulation of cancer. So looking at the the watercress phenylethyl isothiocyanate, there's really good evidence. So if you put into Google PEITC and cancer, you'll see all the work that's being done at the minute. So for example, if you there's been studies where they give people synthetic PEITC who are having radiotherapy for breast cancer. And if you supplement people with PEITC, you have a better outcome at the breast cancer from the radiotherapy. So what the PEITC does is it's able to switch on the death genes or apoptotic genes and switch off the survival genes of the cancer. And what we also see is it exhibits an an anti-inflammatory function. So it's got a modulating effect through inflammatory pathways. So the surrounding tissue damage which you get from radiotherapy is actually reduced as well. So we just by blending it up and tasting it, we realised that after we blended it up, we're actually disrupting all these cells and converting this gluconasturtium, which is the precursor to the phenylethyl isothiocyanate, we're converting one to the other. And the reason it's getting more peppery is because this PEITC is just being produced.
Dr Rupy: By by preparing it in the way you were doing, you were actually increasing the concentration of the isothiocyanate that has all these potential benefits.
Dr Kyle: Absolutely right. And we we figured that out just by tasting it because we the paper said it's the PEITC which gives watercress its pepperiness. So the idea is a cow would come along to a river, chew the watercress, it doesn't like the pepperiness, so it goes on to another plant. So it's a stress, it's effectively like a stress hormone for the plant, but it happens to have all these interesting properties. So we we often get asked, you know, well why why do you need to blend it up to make the PEITC? Why can't you get it from chewing? Well, we when we blended the watercress, we found that it took two hours to convert all the glucosinolates into PEITC. So you probably could do it with chewing, but you're going to have to chew each mouthful for about two hours, which I think it would probably blow your head off with the pepperiness by that time. So a complete side route that we're going down now is we've managed to concentrate this PEITC into watercress. So we've got a team in Greece who have been working on some molecular genetics work and and sort of cellular mechanisms to look at whether application of our extract into melanoma models could potentially improve treatment or could prevent the the incidence of skin cancers. And they've got various ways of various ways of testing that. So this is a completely different thing that we, you know, that we've come across without realising that we were going to. So from a from an inflammation perspective, it's interesting. So we're doing some work looking and testing this new anti-inflammatory pathway because clearly for us in nappy rash, it would be great if we can block ammonia and stop the inflammation, but there's probably already ammonia there anyway, which is going to make some inflammation. Well, if we can show that there might be an anti-inflammatory pathway there as well, then that's a second mechanism.
Dr Rupy: Yeah, yeah, so you've got a dual dual mechanisms as to how to treat the overall impact of nappy rash.
Dr Kyle: And that was all just, you know, from blending it up in the kitchen and and tasting it while we were doing other things and realising there was a change in the in the taste profile. So we're now looking at, you know, different things we can do. So if we were to heat the watercress first of all to denature the myrosinase enzyme, then we can just be left with something which is full of these glucosinolates when we disrupt it because the enzyme has been inactivated. There are potential benefits for us doing that as well. So we've got five or six different preparation processes which can completely change the profile of both the flavour but the chemical composition of the extract that we're left with. And similarly, you know, we've got mechanisms where we can retrieve the fibre. Now, watercress fibre, very long chains. You can make plastic out of that fairly easily. So, you know, there's there's interesting things that we might be able to do with that and with, you know, with a few other things as well. So the more that we're looking at how we can prepare and change the watercress, the more we're realising that actually there's there's a whole lot, there's a massive potential. So we started out looking at nappy rash. We're now looking at, you know, modulating epigenetics for various cancers. We're looking at whether we can have anti-inflammatory functions. And we now know that, you know, going back to urease inhibition, there are five or six other other conditions out there where urease is implicated. So Helicobacter pylori, which is a bug that lives lives in the stomach and causes gastric ulcers and bleeds and and can cause lymphomas. It survives the acidity of the stomach because on the outside of its cell wall, it's got a urease enzyme. So it effectively covers itself in a blanket of ammonia to buffer the stomach acid. And in papers where you've genetically knocked out the urease genes of an H. pylori, it can't survive in the stomach. So we've been doing some work with the University of Bath. They've got a computer model of the crystalline structure of an H. pylori urease enzyme and we've shown that our urease inhibitors all dock at different sites and inactivate the enzyme in different ways. So whereas with the current urease inhibitors, you've got one molecule. So one of them might be acetohydroxamic acid, that binds at a particular site. We know that we've got at least seven urease inhibitors that some of them bind outside the active site and change the conformational structure. Some of them bind in the active site reversibly and non-reversibly. So we've got a really good spread there against this urease, which means that we we believe we can knock out the urease enzyme. If we do that, H. pylori dies. So then we're into the territory of have we made a new antibiotic?
Dr Rupy: Yeah, yeah. I was going to, I didn't actually realise that you had multiple different ways in which urease is inhibited using the singular product.
Dr Kyle: Yeah, so so we we've got seven inhibitors. Now what's useful for us is if you look at the urease enzyme, it's relatively well preserved across nature. So some plants have got urease enzymes as well as inhibitors. That urease enzyme is a nickel-based metalloenzyme, so it's got nickel at its core. It's very similar in plants to what it is in proteus, into what it is in some fungi who've who've got it as well and other bacteria. So where we're doing this this theoretical docking work with this computer model on an H. pylori urease, that should be very transferable over to other urease enzymes. And the fact that we've got so many different ways of inhibiting it means that that transferability, the likelihood is increased. So we, you know, so the other conditions apart from H. pylori, we've got struvite kidney stones, some water infections, something called hepatic encephalopathy, which is where ammonia rises when you've got liver cirrhosis and crosses the blood-brain barrier. All these conditions could be could be effectively treated. So, um, what what we're doing now is we are hopefully going to going to get a contract for the continence work. We need to take on some more funding to build a biorefinery. We're then looking to do, um, an application to the Food Standards Agency in the UK and the relevant party in the EU, um, because this is going to be seen as a novel food. So it's going to be an 18-month application process to get this protein byproduct and the watercress extract registered as a novel food. Once we've done that, we'll be able to start the oral clinical trials because we'll have all the toxicology studies done and we'll be able to give it to people who have got H. pylori infections and we've got some good links with some hospitals in India where it's quite rife and uh see if we can actually prove this is a new antibiotic.
Dr Rupy: This is this is particularly interesting, I guess, um, and perhaps you can add some clinical context as to why a substance that impacts H. pylori could be so useful in general practice where we see a lot of infections with this bug that can lead to gastritis.
Dr Kyle: Yeah, well, what's interesting with H. pylori is if you look at at at the prevalence of H. pylori across countries, as the as it goes up, as the prevalence goes up, you tend to see rates of gastric cancer go up as well. So in places like Colombia, um, South Korea, the majority of people are colonised with H. pylori. Gastric cancer is in the, you know, the top two or three cancers, whereas in the UK, it's currently 12th behind the ones that we would think of common cancers. So, you know, lung, colorectal, breast, prostate. So, in in these other countries, if we can the dream really is to look at population level dietary supplementation with a urease inhibiting extract that we can make and we might be able to crash the rates of gastric cancer. In the UK, whereas, you know, gastric cancer is only the 12th most common cancer, A, it's not a very nice cancer to get. It tends to be a particularly horrible one. But we also know that the resistance rates of H. pylori to the various antibiotic regimes that we've got are getting worse as it is for for other conditions as well. Now, because we're the way we're targeting the urease and because the urease enzyme is relatively well preserved across nature, it's going to be very difficult for H. pylori to develop resistance to these to these molecules because they're acting extracellularly and it's not going to be able to change the structure of the H. pylori of the of the urease sufficiently to prevent that that inhibition because nature just hasn't done it to date. So we and you know, it might be the case where we don't demonstrate an antibiotic function, but what we do is we make the H. pylori effectively a bit sleepy and a bit quiescent. So yes, you've still got the bug, but it can just sit in your stomach for decades and not cause you any any difficulties. It's the same argument that we have at the minute with urinary tract infections. So you'll know as well, you know, if you looked at if you took urine samples from 100 women over the age of 80, the vast majority are going to have a positive urine dipstick because they've got bugs in their urine. But there's a difference between having bacteria in your urine and being asymptomatic to having an infection where those bugs are causing you difficulty. And we hope that if we can, um, get through the food standards agency and start a trial, taking on this watercress extract, it might not necessarily kill the bugs, but it might just rain them in and sort of get that balance back, that symbiosis. Um, and just again, make make them tolerated better, um, in the gut. So that's that's what we're looking at at the minute. It's going to be a long process, you know, we're we're looking two years down the line just to get this, um, get the licenses through that we need and then be able to start the clinical trials. But certainly from H. pylori in particularly in other countries, that that's a really big one for us if we can get that right.
Dr Rupy: Yeah, that's huge. I mean, like in the context of antimicrobial resistance as well, which is a growing phenomena. I mean, we had Dame Sally Davis on the podcast a few months ago talking about just how much of an issue this is. If we can find strategies to induce dormancy, like you suggested of these bugs, or at least render them a little bit less capable such that they're more susceptible to the current suite of antimicrobials that we have at the moment, this is really game-changing stuff.
Dr Kyle: Yeah, you're absolutely right. And we we know that, um, proteus, for example, if you knock out its urease enzyme, it doesn't die. But the the urease is a virulence factor, so it helps it to survive and colonise areas through various ways, through biofilm formation and through other other things. Just by knocking out that virulence factor, I I think this is potentially a better strategy than killing off the bugs, having a more of a bacteriostatic effect and just raining them back in because we're sort of meant to have bugs on us. That's that's what we're meant to do. And when we give antibiotics and we wipe out half of our gut flora and half of our skin flora, that's not always a very good thing to do. And as you said, you know, the rates of antimicrobial resistance are going up. So fingers crossed, you know, the we hope that the watercress extract on its own could have that kind of dormancy effect. But in bugs where you really do want to get rid of them because they're still causing a problem, it may be that knocking out that virulence factor opens the, um, the bug up to being susceptible to a wider range of antibiotics, shorter courses of antibiotics, lower doses of antibiotics. And then with that, you'll hopefully get, you know, less chance of resistance, less side effects, you know, less of the diarrhoea and vomiting because you've obliterated half your gut microbiome. Um, and and, you know, that's that's what we're hoping to do. Um, we know, for example, that with wasabi, wasabi has a particular isothiocyanate called allyl isothiocyanate. Loads of information at the minute being published around the role of allyl isothiocyanate in the disruption of biofilms. So, you know, if you're looking at if you're looking at catheters, for example, who often get blocked and crystallised from biofilms, well, could you use a wasabi and watercress mix? And then what about mustard seed and the sulforaphane from broccoli? They've all got a slightly different thing. So, you know, we're hoping down the line, could we make a mixture of different brassica families to just have all these different isothiocyanates with all their relative effects as a treatment, which one single molecule isn't going to be able to do synthetically. So for us, you know, we and it's that reason that we've got so many different molecules acting that we're never going to be able to make this a synthetic, um, drug because we think there's benefit in having lots of things working synergistically. So we're always going to be working from watercress down. The difficulty that's going to bring us is if we prove this works fantastically well for, let's say, struvite kidney stones. So we knock out the proteus urease, the pH of the urine comes down, things don't come out of solution, you don't get struvite kidney stones. The stance of the MHRA at the minute is that they will not license anything which has been extracted from a plant, you have to synthesize it and then demonstrate purity above a certain threshold. So that potentially leaves us with a bit of a problem. I'm hopeful that with the current, um, interest in CBD and extracting direct from the plants, with advances in hydroponic farming, you know, vertical growing, sterile techniques, that stance may change or there may be, it might not be a true license, but it may be an endorsement, it may be a sort of a sign of acceptability from the MHRA that yes, this can work and granted there might be very, very strict growing schedules, but for me, if we can grow things, if we if we find the perfect watercress plant, because we know there's about 50 species and we're going to spend some time splicing and chopping and changing watercress to get, um, to get the right species. But if we can prove, you know, you take this species and you grow it for this amount in this water, this pH, all the rest of it, and then we can harvest it and time after time demonstrate purity above a certain threshold, I'm hopeful that's going to be seen as acceptable and then we might be able to start licensing it as a medicine.
Dr Rupy: Yeah, definitely. I mean, I I like as you're talking, all I want you to do is to create a company that everyone can invest in and just throw money at and then you can spin out different companies thereafter because I think it would be one of the best investments that anyone could make.
Dr Kyle: Unfortunately, if I just strap myself in watercress anymore, my shareholders are going to shoot me. So, uh, I'm going to have to do that down the line, but uh, I'll know where to come for the future.
Dr Rupy: Yeah, definitely. Keep me posted.
Dr Rupy: Thank you so much for listening to this week's podcast. I really hope you found that inspiring and exciting. I mean, like the untapped potential of ingredients like blackcurrants and other brassica vegetables and corn and whole grains and all the ingredients that we have littered in our supermarket shelves, I just think is super, super exciting. We didn't actually veer into a conversation about growing and how that impacts the phytonutrient profile of foods, but I'm sure we will do that at some other point. As always, if you want to support the podcast, do so by subscribing on Apple or hit follow on Spotify. It really helps the rankings, which means we get more listens, which means I can do more pods, and do sign up for the newsletter at thedoctorskitchen.com where I send a weekly wellbeing trio of things to do, something to eat, listen to, watch or read that will brighten up your week. And for the studies and some other links, you can find them on the show notes at thedoctorskitchen.com/podcast. Just look for uh watercress as medicine, the episode name, and I will see you here next time.
