#419 Mark Kendall from WearOptimo: How Micro-Needles Are Quietly Replacing Blood Draws

0:00Welcome to the Health Tech Podcast. Here we talk about everything healthcare and technology. and I'm your host James Summery. Hey everybody, delighted to be joined this week by Mark Kendall, founder of Wear Optimo and we're going to be talking about something close to my heart as an ex-anesthetist. Hydration, fluid management but not in a boring sense as we would call it a fluid management in anesthetics. So gutted if you sit in your anesthetic exams and listening to this expecting to learn something We're actually going to be talking about this in terms of Formula One drivers and very cool wearables and stuff.

0:42So yes, Mark, sorry for butchering the description of your company there. I'm sure we're going to talk about that in a bit better detail, but welcome to the Hultec podcast. How are you doing? Very well, thanks, James. Good to see you. Yeah, you too, man. So with that accent, I assume you're calling from Australia or are you based somewhere else globally? No, no, calling in from Brisbane, Australia. It's late at night here and morning there. no doubt. Perfect. Absolute pleasure to have you on. I love these kind of episodes because we can actually geek out on some technology. I can flex some, or I can try and flex some medical knowledge that I've still got knocking around in the back of my mind.

1:20But I do think it's interesting to talk about hydration. And obviously we're going to talk about it in some very cool stuff that you're up to but the way that the body handles fluids is so unbelievably important but it's not a sexy topic it's just not it's just not it's not sexy if you're a medic it's not sexy if you're not a medic but the importance of it is I mean it's frankly just ridiculous how important this is so to be building a company in this space I can imagine from a healthcare and a health tech perspective once you start talking about it to the right people you end up getting quite a lot of attention on this and it comes down to the application of it so for something like you're doing with wearables and micro needles and applying that in elite sport and things like that there is there's a lot to be excited about here for someone like me so I'm very much looking forward to getting into this with you but before we talk about the company and everything that you're up to there why don't you start with your story so what where does this begin are you from an entrepreneurial household are you're you're you're from a long lineage of founders and entrepreneurs or is this something that you got interested in at university where does this all begin for you it's a great question I've always been curious about how things work and if you see something that you think you can do something to help with you you you deploy your skill sets to it.

2:51So that's always been my outlook. I think above all, I see myself as an engineer and the different labels and titles I'm founder and CEO were Optimo, but I just see that as tools to express my inner engineering DNA, if you like, which is to get things done and make a difference in a good way. So the way I became a biomedical engineer was not a straightforward journey. It It was actually, you could call me really an accidental biomedical engineer. So I love rockets, aerospace, did my PhD in rockets. It was in hypervelocal aerodynamics. I worked on one of the world's fastest wind tunnels. It was founded by NASA.

3:33I was supposed to go to California to work on rockets there. Had a job lined up to do it. And yet, I don't know if this happens too much, James, but a two-minute conversation just changed everything. I met someone. yeah I met someone at a conference he came up to me he said he enjoyed my presentation I had this idea to use rockets to fire vaccines into the skin and I thought that sounds really interesting and and and he said he asked if I could come and work with him and so I thought about it and I thought well I had two questions at the time one was where are you doing this work and he said at Oxford University and the second was would I get a chance to row and uh as in being an oarsman and he said if you're good enough uh so that changed everything and of course there was process to get into Oxford it wasn't just a walk in the park but six months later I was at Oxford instead of California and um did you make the boat race crucially the crucial question here did you get in that Putney water and get in the boat?

4:37No, I was in, I did row for my college in the first eight for three years, which was wonderful and invited to the squad for the blue boat. But actually, strangely enough, declined. You declined it? Well, yeah, there's layers to that answer. But one of them is, James, in my heart of hearts, I probably knew I wasn't going to be at that level. There was a non-Olympic year. But also on top of that, I wasn't a student. I was a young lecturer and just full on working. And the first commitment was to spend six weeks in Brazil in a training camp. I just thought, well, I'm married and working full time and rowing full time.

5:22So something's going to, I'm going to have to choose one. You can't do everything, Mark. You can't do everything. And also as well, the boat race is like, it's quite a funny one, isn't it? because it's actually harder to get into those boats than it is to get into any other boat in the entire world. It's actually easier to get into an Olympic team than it is to get into that boat race because that boat race is formed of Olympians from multiple countries that end up at that university. So it's the hardest boat to get into. It was full on, but wonderful time over there. It changed my life. My son's just turning 18 And he just competed in the state rowing championships here and came second in his crew.

6:06So it's wonderful to see that progress. But coming back to answering your question, so as a result of being over there, that changed my life as a biomedical engineer. And I helped take forward that technology, became Ox's most successful spinoff company up until recently. Wow. So it was a company called Powderject. uh so it's like a real life star trek device that fired gold microparticles into the skin at 1500 miles an hour uh sort of small rocket so i was born as i was brought in as the rocket guy to really sort that out and and did uh but then but became exposed let's just zoom in on that second mark so firing gold particles at the skin to what end what was the reason for doing is it the purpose so they're very very small microparticles that's very important right right and um rather than shards of some gold bullion yeah correct yeah yeah so very small particles coated in dna uh dna vaccines right and um the idea was to fire them into the skin to transfect the antigen presenting cells in the skin to make vaccines work better and that's the concept.

7:21So it's actually a precursor to what we now know as RNA vaccines. So this was kind of an earlier development. And so I was there for eight years at Oxford and, of course, rowing aside, it was an amazing innovation apprenticeship for me. So the teaching and the butler and the college, all of that was there and that was amazing for a young guy coming out from Australia. but this innovation apprenticeship, James, was incredible. So worked with amazing people, learnt how to take things forward, how to work in interdisciplinary teams, but also learnt about biology from an engineering perspective and was blown away by how variable and how messy biology is from an engineering point of view, like the skin, the physiology of the skin.

8:09And interestingly, the rocket stuff wasn't the hard stuff because I kind of knew that. Well, I did not. But the hard stuff was the skin. I discovered the biology, the biological need. That was the hard stuff and became interested in that. And that led me on a pathway to this conversation today. And to be very, very brief, after taking that forward, Pfizer ended up buying the technology back in early 2000s for about a billion dollars or so. and it was a unicorn before the term existed. But what do you do after that? I was 31 years old, right? That had all happened and I thought, well, it's sort of less fun now because it's with the mothership in New York, et cetera, et cetera.

9:01So then Bill Gates put out a call for better vaccines in the developing world. Him and Melinda created the Bill and Melinda Gates Foundation at that time. And I saw that as a call for arms to really get cracking as an engineer to help in that space. So I tried to make that other technology work. It wouldn't. So I took a step back, encouraged by my colleagues at college, and learnt immunology. So I was giving lectures in fluid mechanics and engineering topics and then jump on the bicycle and attend immunology lectures and map the skin's immune system and designed a device from the ground up to meet that need.

9:42And that's called the Nano Patch for Needle-Free Vaccine Delivery. And it's placing vaccine directly to their cells. Instead of firing them in, it was with microneedles. Yeah. And around that time, James, I was talked into leaving Oxford to return to Australia and to the University of Queensland as a professor of biomedical engineering. I think I was about 33 or 34 at the time, years old, and to take forward this vision. And after my exposure at Oxford, that's what I said about doing. And it came to pass. So I proved out the technology in a research group setting, founded a company called Vaxxis off the back of that experience.

10:22And like my mentor in Oxford, I was a full-time professor, but effectively a full-time exec in Vaxxis as well. So I did that for about five years or so. And then around 2015, 2016, so Vaxxas is still going forward, to be clear, and I'm still a shareholder in that, and I wish it every success and foundational inventor, et cetera, et cetera. But it was time for me to do the next thing after doing that for about 11, 12 years or so. And did a sabbatical at Harvard and worked with Bob Langer, the co-founder of Moderna there. Wow. And around that time, these guys came out, the early version of the Apple Watches.

11:03Yeah. And, James, I was blown away. I immediately knew that they'll be held back in gaining access to the signals that matter because of the way they work with the skin, because they've worked with the skin for decades at that point. Yeah. And immediately set about coming up with a better way to go about that, which has led to the journey of Wear Optimo today. Wow. That's me trying to compress 27, 28 years into a few sentences. You talked about the skin and you talked about the messiness. That was the word that you used. And biology, especially for physicists and mathematicians, as soon as biology comes in, it's just disgusting because it is just an absolute mess.

11:42And it's just, it's not clear. It's not pretty. It's not logical. And trying in any way to make a deterministic model based on human biology is, you're just barking up the wrong tree basically although that's obviously the the ultimate aim would be to have what would be a full digital twin in inverted commas much like mark webber one of your in you know investors in uh in the latest company would tell you about how they model formula one companies um i'm sure companies cars even and uh yeah exactly have a full working model of a car to see what a change in an angle of a wing would do wonderful if we could manage through that for the entire human body and all its process but obviously we can't but i'm interested in like how you would categorize the messiness of the skin what is it about the skin that is so messy and difficult when we are trying to figure out innovations for the future that involve the skin yeah so it's messy but it's beautifully messy so uh what i mean by that is uh there's so many different things when we look at it there's many sources of variability with the skin right So I'll just give you one example.

12:52With the rocket technology firing microparticles into the skin, when we nailed the rocket, when all the microparticles hit the skin at the same speed, exactly the same speed, all the same size, you'd think they'd go to the same depth in the skin. They did not. There was this range of variability because that's the way the skin is. But I've learned that there's beauty in the variability. It's the variability that creates the ability for the skin to handle all manner of different circumstances. If it was on a knife edge and only suitable for a couple of different things and didn't work in a whole bunch of other scenarios, then that wouldn't work.

13:34So I've developed a deep respect for that variability and seeing the beauty in it. But I can tell you the first time, James, when I looked at that, it blew my mind because just like you touched upon in more classical versions of engineering where you can characterize a material like steel or aluminium to 0.01 % of something. It's nothing like that. And so, but then that's where the elegance is, but that's where the challenge is. Okay, so how do you deploy engineering thinking into that setting, right? So how does that work? Because the standard rules are out the window. So that I find intriguing.

14:17And so you need to let go of trying to get to the same level of resolution of an answer, but more gain really key insights on how the interface with biology works. I find that interesting. Don't go in with a widget and just try and apply it to different various different things get curious about the core physiological need and design something from the ground up to meet that particular need and respect that interface and i suppose at that if i that that one sentence is probably encapsulates a method that i've deployed for the last couple of decades now really interesting and actually to use words like curiosity and respect when it comes to human biology i think is fascinating because it's almost that well there are so many scientists that i speak to on on here and in other conversations and you know even jess jessica and i like my wife and my co-founder in some x like we're you know looking at early stage companies now to to invest in for an angel perspective and things like that and having these conversations it's it's so interesting that people that can be real experts in a field scientifically or medically and clinically will still just have this really healthy dose of caution and respect when it comes to a you know a research question and you know there's a company called booby biome that that we've you know we're involved with now and and you know those those research scientists who are expert in the microbiome of breast milk and the infant gut were just so humbled when they initially looked into it thinking oh we can just map this stuff they'll be we'll just create a database and Lydia we had on the podcast talking about this oh yeah we'll just we'll just map the database of the microbiome um and then we'll just figure that out and then all of a sudden they realized like I mean the the punch line to this was most of the bacteria were anaerobic and therefore they just couldn't detect them because they've just exposed them to oxygen in their normal process and all of a sudden like they just couldn't and they were panicking lydia was saying she's panicking because i've just taken this investment thinking i mapped this database really quickly and all of a sudden i've got zero results like what on what on earth is going on and you know you can you can have done this for your whole life and then just be humbled by such such a minute thing as that as just exposing a group of bacteria to oxygen that wipes them all out and then all of a sudden that becomes your biggest realization and then all of a sudden the anaerobic storage products come out and that's the innovation and just all of these things down the line from from just having this healthy dose of respect as well as curiosity and i see this play out in the adoption in health care as well which i'm sure that we can go on to talk about and all the rest of it but i think that is so so so fascinating um that you just have to have this level of respect but the question i wanted to ask you actually was was more technical than that you mentioned you mentioned a rocket that that blasted this at the skin and again that's interesting because i'm sure for listeners will be the same as me when they think about a rocket they're thinking about something that elon musk is firing off the earth into into space and that seems like a an obscenely high level of propulsion to be throwing anything at the skin but what what's what's the what's the similarity here like what what what is the rocket technology in inverted commas that is actually firing something at the skin again the reason i ask is i think there's learning here for clinicians listening or people in health tech listening that can get an idea from this as to what what is the innovation that you're throwing at the human body that relates to a rocket we might fire to the to the moon or mars so the the another name for it is it's called a gene gun some people have heard of a gene gun before and as a foundational technology rocketry in general it's it's a it's i believe it's the only technology that scales 10 order of magnitudes right so what i mean by that is elon musk's rockets north of 100 meters long and you go down so 10 meters one meter that's two orders of magnitude then it's got you 0.1 and it goes it goes down to nanoscale rockets and wow okay the print the principle the principle deploys across the range so interesting uh it's it's quite interesting and so where we were within it was rockets about that long uh so So it looked like a real-life Star Trek device, but instead of it going like that, it was creating very high-speed flows with helium, high-pressure helium that you released quite quickly, and there's a bunch of mechanisms to set up this high-speed flow.

19:15But the flow wasn't to create thrust. It still did that a bit, and we had to deal with that. It was to – you had microparticles that you can train within it, and it will accelerate those microparticles to hit the skin. Sure. wow fascinating um before we talk about where optimo and how you start applying all of this and the microneedle side of things the last thing i want to talk about in your background is um the very very beginning you mentioned that the companies that you've built are in it somewhat of an expression of yourself i love that method of thinking because that's that's sort of how i feel about what was definitely want to speak to people on this podcast that people end up expressing parts of themselves in these vehicles that can again again sort of like live on without them in a way like as you've talked about you know you move on for a company and a lot of your thinking and thoughts and all that sort of stuff is that a framework that you kind of relate to is that what you're hoping to achieve these kind of areas of expression around the world in different companies and things like that and is that yeah is that i don't know is that something is that is that sort of the the picture that you imagine of of having things live on without you Absolutely.

20:23I mean, we've got to get used to that idea because our lives are finite anyway. Yeah. We're only, I'm sure I'm not original in this thinking, but we're just tourists on the planet, right? So that's what we do with it and how we can be as useful as possible. So that's just how I look at it. So if I didn't try and apply that approach, James, that you just talked about, then there's very, very few things that I'd be able to do or work on. Yeah, okay. But applying this approach and teaching people how to do it. So one of the things within We're Optimized example is that we're creating these innovation apprenticeships like what I received at Oxford.

21:05So for the next generation are learning how to do it because they're learning how to build companies. So if you're good enough, I mean, it's all merit-based, of course, but we've got people that are only just two years out from their undergraduate degree conducting clinical trials, as an example, right? So if you're good enough, you'll progress quickly and get exposed to a lot and then learn that craft where, I mean, my goal is, of course, for We're Optimate to succeed and create that major impact in healthcare. But on top of that, the younger guys, and particularly within the team learning how to do it so then they can go and do something like this in their own right as well whatever it's going to be love it so let's talk about where optimo and in fact first of all can you tell me what a micro needle is why a micro needle is important in the future of health care and health tech and then talk about where optimo for me sure so of course we all know what needles are they've been around a long time and they put things in the body.

22:11We know that. But there's many, many limitations associated with the needle. Start with the obvious, which is people don't like them by and large. So needle phobia, about 20 % of the population have a thing called needle phobia, which means that they will actively avoid whatever the treatment is that is on offer by that vehicle. So it's an invasive technology. Now, if we move into the world of wearables now, and I'll come on to the function of where microneedles fit within it. In the world of wearables at the moment, we're at a really interesting point. So by and large, today's traditional wearables, if you want to use that term, like a surface-based smartwatch, they use light, right?

22:58They're a light-based approach that's on the skin. And that works for heart rate. That works for a few simple things. But the skin, you know, we talked about this respect for the skin, this respect, not disrespect, this respect for the skin is it's an amazing barrier. And it does a great job scattering light and messing with it so that you cannot gain access to the signals that matter the most. OK, so light doesn't work. So what's what's working then to gain access to biosignals? Well, if you look at continuous glucose monitoring sensors, James, have you got any experience with them or you've dealt with them or talked with people?

23:39Yeah, we've had Dexcom on here and back in the day. And yes, we're fully aware of them. Yeah. So Dexcom is a great exemplar. Dexcom, Abbott, ones like that. Right. So they've changed people's lives. In fact, Abbott's Libre device. Yeah, we've had them all talking about Libre. Yeah, it's considered the most successful medical device of any kind. Wow. I think it's sales or like, I don't know, let's say it's$10 billion a year from that device, but put sales to an aside, it's the millions of lives people with type 1 diabetes that's completely changed their life. And that compared to the prick based approach, like taking your blood, it's fantastic.

24:23What you don't see in the advertising brochure is the size of the needle for those devices. It's about 5 to 10 millimetres long. So it's a significant needle that's implanted onto your arm. Great if you have diabetes because the other options are awful. But if you're thinking about getting beyond the Apple Watch and getting access to signals, light-based approaches don't work. and a lot of people don't want to have a needle at all. So we know this, and off the back of that experience I was telling you about before with the vaccine delivery approach, I'm effectively a pioneer of the field of microneedles.

25:10I've probably got about 150 patents in that space. Wow. And so over about 25 years, I've just learnt the art of doing that, and it's probably, James, just like any other expertise you've probably come across as the nuances, like things that if you didn't really know, you wouldn't think makes much of a difference, but it actually does. So knowing those nuances. But my point is where microneedles come in in the world of sensing is that I've identified you only need to go a hair's width into the skin to gain access to the signals that matter. Okay. Wow. Wow, a hair's width into the skin to get the signals that matter.

25:53Wow, that's not what I would have thought. No, indeed, it's even better when you think about the world of hydration, James. So one of the reasons why we've gone after hydration is not only the huge unmet need, which we'll get into, but it's an elegance of the interfacing with the skin. Because when we dehydrate, of course, you already know this, James, but this is for the audience. I've probably forgotten it, Mark, so don't worry about re-educating me. It's been a real awakening and a learning for me about how hydration and dehydration works. But the first big surprise for me is that when we dehydrate, we don't dehydrate uniformly through the body, right?

26:35There's different things that dehydrate more than others. And then you think about why. Why does it do that? And the body's quite elegant. The body's saying, well, I want to prioritize certain areas and pull fluid from other areas to maintain that. So the areas that it's prioritizing is the blood and some critical organs like the heart and your brain. If they're gone, you're dead, okay? So what that means then is you pull fluid from other locations of the body to get into the blood, to maintain your blood as long as possible, okay? And the biggest water tank, and I apologize to medical doctors, as I'm talking about this as an engineer.

27:18But the way I look at it is this way. So the biggest water tank in our body is the skin. So what that means is when we dehydrate, fluid is ripped from the skin and sent into the blood. So that's been known by quite a few people in the field. But what we found is that there's one layer within the skin, just below the tough, dead outer layer. It's called the viable epidermis. It's mostly interstitial fluid. and that is the zone that changes the most interesting and so what that means then is that where we tap into that with our micro electrodes and we do bi-impedant sweeps and pull out ultra high fidelity signals but unlike what others encounter when they're looking at other things trying to pull out other things from the skin skin's usually a lag indicator compared to blood so that means you get a weaker signal compared to blood that's that tends to be how it works and i've studied this and worked in this area for a while it's flipped here so in the world of hydration the skin is a lead indication in indication compared to the blood wow and so we've found this this this beautiful interface where we gain this great signals and do it with a better resolution uh than what blood does so and james uh we just completed our clinical study exploring this and of course you can strip down you can dress up whatever company you like but when you're in the world of health tech biotech in the end you have a business hypothesis right so something has to work technically and everything else in order things to to fly so our in our clinical study the overall hypothesis is that by doing this we the thing would work and we'd measure hydration and it's come to pass that that's the case and it's come to pass that it's performing better, our sensor is performing better than gold standard blood draws.

29:17And in part that's because of what I've just said, where the skin's a lead indicator compared to the blood. And a little side note, James, is you've got to be a little bit lucky as well. So we're lucky in the sense that where we are in the world right now with what AI is able to do. So we pull out great signals with the sensor. But if you look at it with the naked eye, they're just ultra high fidelity signals. They're clean. But the naked eye does not discriminate what your hydration level is. So we needed to create a complete AI model over about three, four years, multiple millions of dollars investment to do that, to be able to read those signals.

30:01So, James, we tried to do that five years ago. where ai was at that point in human history it wasn't available so this is where we're lucky that the tech stack stacks up just at the right time for us so much building companies is timing um so awesome and and really fascinating i want to dig into the some of the specifics here so So what exactly is the microneedle measuring in the viable epidermis? And how is it doing that from a technological standpoint, leaning on the fact you're an engineer here, so I can ask these quite specific questions with you. So it's electricity. So they're microelectrodes.

30:49So that's the first thing. The simplest way of thinking of it is two electrodes in the skin. And we send a current through it. We send the current at a range of frequencies, and that's very important, okay? And the term for it is called bioimpedance, but impedance is just another term for resistance, right? And so what happens, James, is as the skin changes its level of hydration, its resistance or bioimpedance changes. And also we do frequency changes because at high frequency, at the ultra high frequencies you get to pick up what's happening within the cells within the skin yeah and at lower frequencies you pick up the interstitial fluid between the cells so we you piece together those two parts of the puzzle so that's that's the that's what we achieve within that layer within the skin that's interesting because for me because that's what makes me now start to believe you that uh you that it can be better than a blood draw because it's a different mechanism and what you're not saying is like oh we do the same stuff but because if you again if you're looking at any sort of clinical picture macro clinical picture of a a person and you're trying to assess dehydration you might look for certain clinical signs that are visible to the naked eye in which case they're far beyond what you're talking about you might look at urine output you might look at the real function you might look at hematocrit or mcv or sodium or like all these things in the blood that that quite you know you can paint a very accurate picture putting all of that stuff together but i guess what you're saying is if we're talking about you know health tech and biotech and a hypothesis that's going to prove something of value for the future you know a piece of scientific knowledge that we can then start to build products down the line from that can create more value then yeah we're talking about earlier we're talking about how can we you know figure this stuff out earlier which is why then actually if you're talking about bioimpedance of the viable epidermis of the skin using micro electrodes then actually i now start to and as clinicians right i'm being somewhat glib but as clinicians we're always going to be we're trained to find problems in things and so we're always we're always going to be skeptical yeah exactly and i think that's healthy skepticism in in healthcare because ultimately you know signals like this that are inferred by clinicians like this is where damage can happen especially with acute kidney injury and like all sorts especially if you're talking about fluid management which you know is an anesthetist and intensivist you know that gets very very important people get quite irate about fluid management and renal physicians and intensive care physicians will often argue quite in depth about the perfect way to fluid manage somebody with various different things so this is so this is important but I think being a different mechanism and being a different biological signal becomes very very interesting and especially when you're talking about now a clinical study how many people were in that clinical study or like what how confident are you based on a clinical study and what's planned down the line from a from an r &d perspective because imagine with something like this in the company you're building r &d and the the clinical I guess r &d of figuring this stuff out has to be like a quite a significant can well frankly spend thinking of it from a ceo perspective and and you know allocating resource so yeah how confident are you at the minute with that clinical study and what else have you got planned to sort of keep i guess proving this that's right so uh what what we're doing is because we're not a university research group and i've done that before and know what that's like our focus is not only proving what you've just talked about but then doing it in a form that's a technology that's translatable so it's the combination of the two so it's actually a big ask uh to do that but that's that's the challenge that that we that that we we set about meeting and yeah so the the clinical trial we we set about doing this by uh we recruited 45 people and they were tested twice okay and the the mechanism for dehydration was uh so there's two arms to the study one one arm is you turn up fully fully hydrated and you go through a a dehydration rehydration protocol that's through exercise so you exercise for half an hour then take on fluids during rest period and then continue that cycle for about four or five hours from memory and then you do another arm which is you do the same thing but instead of taking on fluids you continue to dehydrate.

35:25And James, the construct of the study is that we compare against all of the gold standards. So that is blood drawn, serum osmolality, urine tests as well, mass loss, and occasionally also a full body bioimpedance where you sit on a bioimpedance stand and you have to stay still to do that. So maybe a good way of thinking about what we're doing is instead of having bioimpedance around the whole body where there's a whole bunch of things not sensitive to changes in hydration, like your bones is one example, right? People in the field of medicine are quite familiar with different ways of trying to infer the level of hydration, one of them being a pinch test of your skin.

36:07Yeah. Yeah? Yeah. And so that says your mechanical properties change as your skin is hydrated or not. That's really what they're testing, as do your electrical properties. So all we've done is taken a full body body and pins, but fitted it down into a tiny wearable and we've been able to do that because you're tapping into this highly sensitive location within the body yeah so that's the clinical study and so we've achieved that proof of concept on that which is fantastic so proving that we achieve that performance so that's step one now step two is is taking that forward as a technology through further clinical and field testing and turning that into a product okay and so uh i'm sure you've heard in your podcasts uh that expression that what keeps you up at night right yes it's a classic you know yes cliche question and uh if i'm honest with myself probably a couple years ago it was would that overarching hypothesis does it actually work right yeah right of course and you believed it would work but until that because we're scientists because you have to wait for the science to come in and the science doesn't always play no and so it was a special moment when we realized it works so that's ticks that box now now what keeps us up at night is taking it forward and turning into the product so that's the next step so there's there's many elements to that i love it before we talk about that i have a question just on the science before we move on is do you see the day then that this becomes a new clinical standard for how we measure this and i asked that question in my mind i think there's there's always two levels when we talk about a new technology particularly in in the modern world where we're on one hand i think we're always talking about how new technology can help us with prevention or optimizing the health of someone and i think on the other level we're always talking about uh like accuracy and people in acute issues basically so or you know ongoing issues in a hospital setting or whatever and that kind of thing um do you see this technology being a new clinical standard at one or both of those at any point is this strong and powerful enough do you think and is this a stepwise increase in accuracy enough to make it valuable is it enough of a stepwise increase in what we do now with prevention to help prevent certain things like is the business model there on one or both of those levels does that make sense oh it's a beautiful question uh so the short answer is uh totally uh so right let me explain uh so first is uh the the scale of the problem of hydration uh we we made the call on this about six years ago uh going into this and it was actually uh one of our advisors uh was that the ex ceo of mclaren uh formula one technologies which is just up the road uh from that is just up the road from me yeah yeah yeah yeah and he was working with me and uh whispered in my ear about the the level of the problem of hydration because we we just started the company a massively powerful platform we're building what's the fit what's the application so that led to a cascade of uh you know to this to this where we are today but in the last few years in particular james there's one example like just last year there was an amazing publication in nature nephrology reviews and it was about the scale of the problem of hydration which most people didn't didn't know i didn't know now i've been a student of this for about five six years and what they pointed out was this was that when first up about half of americans are chronically and mildly dehydrated okay now Now, you kind of think, oh, that makes sense.

40:26But you think, well, what's the big deal? Okay, I'll have a drink of water or I'm just struggling a little bit. I'll soldier on. It turns out it's a massive problem because they've discovered that it puts the body into a state of stress, low-grade stress. Okay? And there's many, many reasons for that. It turns out there's a biomarker that controls the kidneys and the kidney function, and it makes the kidneys work in a certain way when you have less blood. It makes them work harder. But that same biomarker also puts the brain into, it releases cortisol as well. Anyway, to cut a long story short, it's such a massive problem that they figured out that it drops your life expectancy by about four years.

41:14Whoa. It increases your incidence of dementia by about 48%. Whoa. It affects everything. and so much so not just their work but the work of many many others there's a push in the medical community for uh hydration to become the sixth vital sign yeah okay now i think there's some other candidates i'm not saying it's the only one but sure there's the five and i keep forgetting what they are but you'll be able to walk me through what they are but uh but there's this sixth vital sign. Now, what's really interesting with that, just as a side note, if it's the work of others, if hydration was considered a disease, it would be level pegging with diabetes in terms of its scale.

41:58So you think, okay, if it's such a massive problem, what are the solutions? And the solutions are extremely rudimentary right now. And you touched upon those. There's blood draws, urine tests, pinch tests, doctors looking into your mouth to see how dry it looks. And it's unbelievably rudimentary. And so what we've been able to do is come in with this solution, which is deployable in many, many different areas because it's a wearable format, feels like a sticker as well because the microneedles are so small. And we've created the first digital biomarker for hydration. but it's in a format of a wearable.

42:42So how we deploy that is, of course, critical, but the range of where it's deployable, it's deployable in clinical settings, and I'm sure we'll come on to talking about anesthesia and how that works and vastly improved operations, et cetera, et cetera. But it's many other settings as well. We're talking about work environments. If you're in, say, an outdoor exposed environment in the mining sector, as one example, It's affected them in many different ways. How your brain works, if you're only 3 % dehydrated, as one example, it's the equivalent of being over the blood alcohol limit with your cognitive function.

43:24And so there's that setting, many others. But in the elite sports settings, you mentioned Mark Webber before. Mark's one of our investors. He used to race with Red Bull, as you well know, and he's managing Oscar Piastri over there at McLaren. And Mark knew the issues of hydration because he knew how it affected him as a driver. Yeah. He talks openly and publicly about a crash he did at one of the Monaco races years and years ago. And the post analysis showed that he hit the wall at something like 200 miles an hour. And a critical reason for that is that his state of hydration at the time was was low and that was his he's quite advanced he was using all the tech that was available but he knew that that was an issue uh so uh there's a massive range of applications and of course we need to focus because we can't do everything all the time and um but the even the just the clinical the scale of the clinical problem with hydration is is huge yeah and it opens it up to this like population level the question being like what if everyone wore this you know what would be the business model if you really scaled this up to population level everyone had one you know it was incentivized by employers because they want you at full cognitive capacity all day therefore you stick one of these on and then give you free drinks in the office and all the rest of it and then all of a sudden you it's really interesting then how like Like, yeah, you're talking about optimization there by the people that are incentivized to optimize you.

44:58But actually, then you're preventing down the line. And actually, that's where it becomes interesting. But even if you're picking up people down that prevention journey, so maybe you're not optimized by your employer to give you them at work. Maybe your sports club or your this or your that or the other. Maybe you're not there, but maybe from a health care point of view, if you've given these in an outpatient appointment or if you're like all of that sort of stuff. have anywhere in your healthcare journey, the GP, the this, that, the other, like, then if there's, yeah, if there's advantage to it at any point down that healthcare model, it gets really interesting, because you're quite right in terms of the cognitive issues, the chronic issues, and the stress on the body, you're quite right that yeah, all these things exist.