Podcasts about live longer

This episode explains why maintaining muscle mass is important for health and longevity. I describe three methods to induce a hypertrophic response and the variables you can manipulate for each mechanism. I also provide some general rules to follow whether you are a novice or experienced with resistance training. _____________________ ABOUT THE BLUEPRINT PODCAST _____________________ The BluePrint Podcast is for busy professionals and Household CEOs who care deeply about their family, career, and health. Host Dr. Erik Korem distills cutting edge-science, leadership, and lifeskills into simple tactics optimized for your busy lifestyle and goals.   Dr. Korem interviews scientists, coaches, elite athletes, entrepreneurs, entertainers, and exceptional people to discuss science and practical skills you can implement in your life to become the most healthy, resilient, impactful version of yourself.   On a mission to equip people to pursue audacious goals, thrive in uncertainty, and live a healthy and fulfilled life, Dr. Erik Korem is a High Performance pioneer. He introduced sports science and athlete tracking technologies to collegiate and professional (NFL) football over a decade ago, and has worked with the National Football League, Power-5 NCAA programs, gold-medal Olympians, Nike, and the United States Department of Defense.   Erik is an expert in sleep and stress resilience, and he is the Founder and CEO of AIM7, a wellness app that provides custom exercise recommendations to improve the outcomes of programs and workouts you already love. It unlocks existing data from wearables and other apps to provide empathetic and scientific guidance that's perfectly in tune with your mind and body.   SUPPORT & CONNECT   Instagram - https://www.instagram.com/erikkorem/ Twitter - https://twitter.com/ErikKorem LinkedIn - https://www.linkedin.com/in/erik-korem-phd-19991734/ Facebook - https://www.facebook.com/erikkorem Website - https://www.erikkorem.com/ Newsletter - https://erikkoremhpcoach.activehosted.com/f/  QUOTES   “The key is using stress and adapting to it and improving. That's what high performance is to me, the ability to adapt rapidly so you can achieve your potential. There are five key pillars to creating the conditions for adaptability: sleep, exercise, mental resilience, nutrition, and community/relationships.” - Dr. Erik Korem   “I maybe have a different concept on leadership. To me, leading is a verb. If you're leading, you're a leader. If you're swimming you're a swimmer, if you're driving you're a driver. If you're leading you're by definition a leader. I define leading as being looked to in a particular moment to make a decision or perform an action based on your unique gifts and abilities. So by that definition, everybody is a leader. All rank and role really describe is how many people are hoping you get it right when it's your turn to wear the weight.” - Clint Bruce "Attention is the currency of performance." - Dr. Peter Haberl “That's what I've discovered in the lives of brilliant, prolific, healthy creatives, is that they have networks of people they leverage in the course of their work. That they learn from, that they were challenged by, that they gave great insight and purview into their own life and work, in such a way that they were able to receive feedback that helped them get better at what they do.” - Todd Henry "Restful and fulfilling sleep enables you to grow, adapt, and thrive. It creates the conditions for adaptation, so you can pursue audacious goals and thrive in uncertainty." - Dr. Erik Korem "Most exercise programs fail, not because the reps and sets are poorly designed, but because the program doesn't adjust for how much stress your body can adapt to that day!. That's why Dr. Chris Morris' research and practical application of fluid periodization is the key for unlocking your performance potential." - Dr. Erik Korem See omnystudio.com/listener for privacy information.

Co-Hosts Dr. Michael and Dr. Barbara Grossman (https://mountaintoppodcast.com/grossman) You've probably heard that those who are in a long-term relationship live longer. Well, my guests are specialists in that area. In this episode, they reveal exactly what we can and should do to make sure that happens. Can you believe there was an 80 year study to find out the truth behind this? What are the baseline rules for making sure you're in the right relationship with the right woman to promote longevity? What if we're already in a relationship that is likely the opposite of that? Even though the premise of this episode isn't completely gender-specific, why is it especially pertinent to men?How do maturity and responsibility intersect with all of this? As we go through different life stages during a relationship, how does the dynamic change that keeps us thriving over the long haul? What is the medical science perspective on all of that? How do menopause--and yes andropause--affect the power of our relationship to increase our overall longevity? You know testosterone levels were going to come up in a conversation like this. What does Dr. Michael have to say about that? What are Dr. Barbara's ways to 'socially engineer' your relationship right now to propel you to a long, happy and healthy life ahead? How does the frequency of sexual activity affect longevity, especially for us as men? Who lives longer, parents or childless couples? And...the most tantalizing question of all: Generally, we do our best to be healthy and look good during our dating days, and yet even though the stereotype is we 'let ourselves go' after marriage, why is it 'old married couples' STILL tend to live longer? Ready for that once-in-a-lifetime relationship that isn't going to kill you? Then perhaps it's time to get on the phone with me for 25 minutes to put a plan together. https://mountaintoppodcast.com === HELP US SEND THE MESSAGE TO GREAT MEN EVERYWHERE === We'll keep the solid, actionable content coming...all for free. If you love what you hear, please give us a 'thumbs up' by rating the show (takes one second) and leaving us a review. As we say here in Texas, we appreciate you!

This week Harry continues to explore advances in "digital therapeutics" in a conversation with Paolo Pirjanian, the founder and CEO of the robotics company Embodied. They've created an 8-pound, 16-inch-high robot called Moxie that's intended as a kind of substitute therapist that can help kids with their social-emotional learning. Moxie draws on some of the same voice-recognition and voice-synthesis technologies found in digital assistants like Siri, Alexa, and Google Home, but it also has an expressive body and face designed to make it more engaging for kids. The device hit the market in 2020, and parents are already saying the robot helps kids learn how to talk themselves down when they're feeling angry or frustrated, and how to be more confident in their conversations with adults or other kids. But Moxie isn't inexpensive; it has a purchase price comparable to a high-end cell phone, and on top of that there's a required monthly subscription that costs as much as some cellular plans. So it feels like there are some interesting questions to work out about who's going to pay for this new wave of digital therapeutics, and whether they'll be accessible to everyone who needs them. Pirjanian discussed that with Harry, along with a bunch of other topics, from the product design choices that went into Moxie to the company's larger ambitions to build social robots for many other applications like entertainment or elder care.Please rate and review The Harry Glorikian Show on Apple Podcasts! Here's how to do that from an iPhone, iPad, or iPod touch:1. Open the Podcasts app on your iPhone, iPad, or Mac. 2. Navigate to The Harry Glorikian Show podcast. You can find it by searching for it or selecting it from your library. Just note that you'll have to go to the series page which shows all the episodes, not just the page for a single episode.3. Scroll down to find the subhead titled "Ratings & Reviews."4. Under one of the highlighted reviews, select "Write a Review."5. Next, select a star rating at the top — you have the option of choosing between one and five stars. 6. Using the text box at the top, write a title for your review. Then, in the lower text box, write your review. Your review can be up to 300 words long.7. Once you've finished, select "Send" or "Save" in the top-right corner. 8. If you've never left a podcast review before, enter a nickname. Your nickname will be displayed next to any reviews you leave from here on out. 9. After selecting a nickname, tap OK. Your review may not be immediately visible.That's it! Thanks so much.TranscriptHarry Glorikian: Hello. I'm Harry Glorikian, and this is The Harry Glorikian Show, where we explore how technology is changing everything we know about healthcare.Two weeks ago, in our previous episode, I talked with Eddie Martucci, the CEO of a company called Akili Interactive that's marketing the first FDA-approved prescription video game. It's called EndeavorRx, and it's designed to help kids with ADHD improve their attention skills.It's one of the first examples of what some people are calling “digital therapeutics.”And this week we continue on that topic—but with a conversation about robots rather than video games. My guest Paolo Pirjanian is the founder and CEO of Embodied.They've created an 8-pound, 16-inch-high robot called Moxie that's intended as a kind of substitute therapist that can help kids with their social-emotional learning.Moxie draws on some of the same voice-recognition and voice-synthesis technologies found in digital assistants like Siri, Alexa, and Google Home. But it also has an expressive body and face designed to make it more engaging for kids.Moxie Video Clip: Hi, I'm Moxie. I'm a robot from the GRL. That's the Global Robotics Laboratory. This is my first time in the human world. It's nice to be here. Oh, where is here, exactly? It's a pretty big world for a little robot.Harry Glorikian: Moxie hit the market in 2020, and parents are already saying the robot helps kids learn how to talk themselves down when they're feeling angry or frustrated, and how to be more confident in their conversations with adults or other kids.But just like EndeavorRx, Moxie isn't inexpensive. The robot has a purchase price comparable to a high-end cell phone, and on top of that there's a required monthly subscription that costs as much as some cellular plans.So, it feels like there are some interesting questions to work out about who's going to pay for this new wave of digital therapeutics, and whether they'll be accessible to everyone who needs them.Paolo and I talked about that, as well as a bunch of other topics—from the product design choices that went into Moxie, to the company's larger ambitions to build social robots for many other applications like entertainment or elder care.So here's my conversation with Paolo. Harry Glorikian: Paolo, welcome to the show.Paolo Pirjanian: Thank you. Hey, for having me on the show.Harry Glorikian: Paolo, you're the co-founder and CEO of a company called Embodied. And and you guys are in the field of, I'm going to call it educational robotics. But this is not your first robotics company, right? Can you can you start by filling in listeners about your history in the consumer robotics field?Paolo Pirjanian: Absolutely. Yeah. So I actually got my education in Denmark. I got a PhD in A.I. and robotics and then moved to the US actually to work at NASA's JPL. Which was a childhood dream job. Shortly thereafter, I got approached by Bill Gross of Idealab, who started one of the earliest incubators, who wanted to start a robotics company. So I joined that company as the CTO originally and then eventually became the CEO. We developed Visual Slam Technology, which is a vision based, camera based ability for a robot to build a map of the environment and know how to navigate it autonomously. That company in 2012 was acquired by iRobot. And we integrated that technology across Roomba and the other iRobot portfolio products to allow them to be aware of the environment and know how to navigate around the home, primarily for cleaning the floors. I was a CTO there for a couple of years and then decided to move on to do something that's been a childhood dream, to really create AI friends that can help us through difficult times in our lives.Harry Glorikian: But one of the projects you worked on, and correct me if I'm wrong, was the Sony's Aibo Robot Dog, right? It's not necessarily educational, but it was aimed at kids. So what sort of drew your focus on robotics for education and socialization, I want to say.Paolo Pirjanian: Yes, correct. Sony Aibo, the robotic dog, my previous company, we developed a computer vision technology for it that enabled the robot to be able to see things and interact with things in the environment. And it was an amazing product, actually, the Sony Aibo. And I've always actually had interest in let's call it mental health. And of course, my craft is AI and robotics. And so after my last company was acquired, I decided the timing is now to go pursue that childhood dream of creating robots that can actually help us with mental health. So we don't categorize ourselves as education in the strict sense because we do not really focus on STEM education. We focus on for children. The first product is for children. It's called Moxie, and it's helping them with social emotional skills, learning, which in layman's term you could describe as EQ, emotional intelligence skills versus IQ, which are more related to STEM type education.Harry Glorikian: Yeah. And it's it's supposed to complement traditional therapy if I was reading everything correctly.Paolo Pirjanian: Exactly. Exactly. We don't believe in replacing humans in the loop. We want people to be treated by humans. But given the shortage and cost of mental health services, there's always room for complementing that with AI and other technologies. And that's what we are doing.Harry Glorikian: So if I ask the question, is Moxie more like a toy that's supposed to be fun, or is it a tool that's supposed to be therapeutic or correct some help help a child that's using it or is it both?Paolo Pirjanian: It's primarily a tool to help children with social emotional learning, things that you would go to a therapist for. The analogy that I use that may be helpful here is really Moxie is a tool to deliver therapy to children. But we we have to make it fun enough for the child to want to take that pill. So in a way, if you use pharmaceuticals as an analogy, a pill usually for children is sugar coated because you want them to take the pill to deliver the medicine to them. So the same way here, Moxie has a lot of fun activities and interesting things that attract a child to want to interact with Moxie. And then during those interactions, Moxie will find the opportunity to deliver techniques and therapies, for instance, to teach the child about mindfulness, teach them about emotion regulation, teach them social skills, to teach them about empathy and kindness, talking about your feelings and so on.Harry Glorikian: I know many adults that may need Moxie for sure. With all those categories you mentioned. Right.Paolo Pirjanian: I agree.Harry Glorikian: But but let's talk about the range of challenges, problems or issues that you've designed Moxie to help with. So can it help with relatively mild issues like shyness, or is it designed to help kids with more severe issues like, Autism Spectrum Disorder or all of the above?Paolo Pirjanian: Yeah, no, it's first of all, you're talking about the audience that it's appropriate for. Obviously, children that have been diagnosed with any neurodevelopmental challenges such as autism need to be trained on social emotional skills. But neurotypical children also can benefit from it. Actually in our customer base, we see a roughly 50-50 split between children that have mental, behavioral developmental disorders. And in the 50% are children that you would call neurotypical. But yet we know even within neurotypical children, they have to deal with things such as stress, anxiety, sometimes even depression. Covid obviously did not help it. It exacerbated a lot of mental health issues for every child, including adults, by the way, as you pointed out. And these techniques and tools that you use from therapy are really the same independent of the diagnosis. Now, some children may need more help with social skills. Let's say if there is a child on the autism spectrum, they may not be very comfortable making eye contact, which is an important social skill to have. When you're interacting with someone, you want to look them in their eyes and Moxie will help them, for instance, with that. And that's maybe something that a neurotypical child doesn't need. So Moxie will focus more on helping them with things such as coping skills, with coping with stress, coping with anxiety or managing anxiety, or even social skills. Like you can talk to Moxie about bullying and it will allow you to talk about it and understand how to navigate that and teach you skills about how to protect your own personal space. A lot of these foundational skills are are the type of skills that social emotional learning includes.Harry Glorikian: So. Let's talk a little bit more about the actual product. And because this is a podcast, I'm sort of like need to talk through some of the features, right? Because they everybody can't see it. But so on the hardware side, you know, the arms, the waist, it bends, the rotating ears, the rotating base, the ears, the face, the speakers, the camera, you know, the program that animates the face and gives Moxie, a personality, the computer vision elements. Right. And then all the scripts of all the different interactions. Right, you know. Why was it important to give Moxie an LCD screen as a face rather than mechanical mouth or eyes.Paolo Pirjanian: Yeah. Let me start maybe take a couple of steps back for the audience, as you said there are no visuals here. Think of Moxie as a AI character brought to real life. Right. So think of it as a, sorry, as a cartoon character brought to real life. So think of a cartoon character that has physical embodiment and it can talk to you. It can smile back at you. We can interact with you with body language and emotions and so on. To your question as to why it required a LCD display. We could potentially consider creating a mechanical face that can have enough expressivity, but that can add a lot of costs on one hand. On the other hand, if not done well enough, it can become uncanny and creepy. So we decided that the LCD display that, by the way, is very is curved because we did not want it to look like a monitor stuck in the head. But it was integral to the design. So it's curved and looks like a face. And what you see on the face is an animated character, Moxie's character, which is integrated very well with a hardware industrial design. So you can provide much more freedom of expression from facial expressions. And especially for children, you want to have a robot that has the ability to show facial expressions. By the way, the intonation of the voice will change as well, based on the type of conversation and the emotion we are trying to capture in the conversation.Paolo Pirjanian: And then the other question, actually, a macro level question becomes embodiment, why did this need to be embodied? Why physical? Why not just a digital character on a screen? Well, so, evidence from neuroscience, from MRI, fMRI scans shows that when we interact with something that has physical embodiment and agency, it triggers our mirror neurons, our imitation neurons are triggered at a much higher level and much wider level than when you're interacting with something just on a screen. And the implication of that is that things you can learn through interaction with the embodied agency have a deeper impact in terms of retention of the information, something that we may be able to anecdotally relate to during COVID. All education went online and the post mortem on that was that te quality of education that was delivered online doesn't compare to what happens in the classrooms. And that's, again, the same thing when it's not embodied. You don't feel that emotional connection. You don't feel an obligation. Many children will just turn off the monitor and walk away, whereas with something that's physically embodied, you feel you can't do that. It has feelings, you feel it has a perspective. You can't just turn it off. By the way, on Moxie, if you look at it closely, there are no buttons on Moxie. There is no input device on moxie like a keyboard or a touch screen or anything else. The way you interact with moxie is the way we interact with each other, using conversation, body language, intonation of voice, emotion, facial expressions and so on. There is one switch actually on the bottom of the robot that you don't see. That's for emergency situations in case something goes wrong. For certification reasons, we have to put that physical switch to turn it off if something goes wrong.Harry Glorikian: So not having played with it does, and only watching the video online, Moxie's voice synthesized like Siri or is it prerecorded? Like, how does it sound?Harry Glorikian: It's synthetic. Yes. So, yeah. So we cast the character of Moxie, decided what this character stands for, what are its values, what is the background story? And then based on that, decided the voice of Moxie, what it should be. And then the way you develop the synthetic voices that you take in neural network and train it based on a lot of samples that we captured from a voice actress in a studio recording hundreds and hundreds of hours of speech from a script. So we have this script and we know how it sounds based on the character's voice recording, and that gets fed into a deep neural network that is trained over and over again until it models that voice. So that later I can just give a text and it will generate a synthetic voice that sounds exactly like that character.Harry Glorikian: And then Moxie seems to emit a lot of sound effects and music. Does that element enhance the product somehow?Paolo Pirjanian: Yeah. So we can underline mood and so on with sound effects or background music. For instance, one of the activities Moxie will suggest if the child is talking about things that are have to do with stress and so on, is a mindfulness journey. Where it will ask you to close your eyes. Imagine you are in a forest or other places as well. There's a library of them. Let's say you're in a forest, listen to the wind and then it will start playing some sound effects in the background and calming music to get the child to imagine they're in that space. For some children that have high sensitivity disorders to certain stimuli like sound, the parents can actually, through a parent app, provide that information which will adjust the settings. In that case, Moxie will actually not use sound effects or any jarring effects that may disturb that child.Harry Glorikian: Interesting. So. Simple question, but is it battery operated? I mean, how long does it last on a single charge? Does it plug in?Paolo Pirjanian: Yeah, it's battery operated because the child usually likes to move it around. You carry the round almost like a baby on your arm. If you remember the days where we had young babies, it was literally ergonomically, it sits exactly right on your arm very nicely. And it has a battery that can run for hours of active usage. And then at night, usually like your cell phone, you plug it in any charges overnight.Harry Glorikian: So, you know, this begs the question of where did the idea of Moxie really come from? Because you don't decide on a whim to build a product this complex. You know, how did you persuade yourself and your investors that the technology is at a point where, you know, it could really make a difference with kids, you know, that have social emotional development issues?Paolo Pirjanian: Yeah. I mean, the idea was sparked probably early in my early childhood, I would say. So, very briefly at a very early age due to a war, my world was turned upside down. And unfortunately, I had to flee my my homeland and seek refuge in another country where I looked different, sounded different and was different. Right? And and unfortunately, as such, you do get rejected by the society. You have a harder time in school. You get exposed to racism and rejection and all these things. So. I remember during that time I saw the first animated short by Pixar. Which was Luxo Jr., the two lamps, mama lamp and baby lamp playing with a ball. Which blew me away that a computer can generate millions of pixels on the screen that are moving to create, to induce or elicit such emotion in the audience. So that inspired me to actually seek education in computer science and robotics and A.I. because before that, as many immigrants you were taught that you were going to be a doctor, so that that's.Harry Glorikian: Or a lawyer.Paolo Pirjanian: Lawyer comes second, but obviously doctor first. So so that inspired me actually to buy a computer and start coding by myself. And I started learning coding and then I decided I'm going to do well in high school so I can get into university and pursue my education. And I did. And to be honest with you, this has been something I've been wanting to do for since I can remember. My previous company, as I mentioned, Evolution Robotics, that was a Idealab company and I was the CTO then became the CEO. I wanted it to do it then, but that's almost a decade ago, or maybe slightly more than a decade ago. We even tried. It was not possible. Absolutely not possible. I remember back then. Just to use an example that I think most people can relate to, voice recognition for even a single command was hard. All of us have had in-car navigation systems with a voice assistant that you would press a button, hold it down and say navigation, and would pull up navigation and say, Enter your address. It will enter the address. And you would have, to by the time you were done, enter the address because it would constantly misunderstand you and then give you options. Did you say A, B or C and no, no, no. I didn't say that. By the time you were done entering the address, you were at the destination. So that was state of the art only a decade ago. Just for voice recognition. Same thing with computer vision.Paolo Pirjanian: My specialty actually was computer vision. Computer vision. Also, we couldn't recognize things very well. And the advancement that has happened in deep neural networks due to the increase in compute power, due to increase to labeled data sets that are available through many sources from YouTube and the Internet and so on. We have been able to solve age-old problems that for decades we were struggling with So it was not possible. The other piece that was probably not possible was that I was not ready as an entrepreneur probably to take on such a colossal challenge of building a product like this. So the stars aligned around 2015 when I decided to leave iRobot and said, You know what? The time is probably right now. And and fortunately, I was able to get some investors that believed in the vision of creating AI characters, AI friends that can help children with social emotional development. And obviously, this technology platform, we will in the future use it for also helping the elderly population with loneliness and Alzheimer's and dementia and so on. We have just scratched the surface with our first products, right? And there is a lot more work to do. But today it's possible. We have proven it. We have a product in the market. A five year old can will interact with it for months at a time without any human intervention. So yeah, so it was a series of events brewing over the last 30, 40 years for this to become possible today.[musical interlude]Harry Glorikian: Let's pause the conversation for a minute to talk about one small but important thing you can do, to help keep the podcast going. And that's leave a rating and a review for the show on Apple Podcasts.All you have to do is open the Apple Podcasts app on your smartphone, search for The Harry Glorikian Show, and scroll down to the Ratings & Reviews section. Tap the stars to rate the show, and then tap the link that says Write a Review to leave your comments. It'll only take a minute, but you'll be doing a lot to help other listeners discover the show.And one more thing. If you like the interviews we do here on the show I know you'll like my new book, The Future You: How Artificial Intelligence Can Help You Get Healthier, Stress Less, and Live Longer.It's a friendly and accessible tour of all the ways today's information technologies are helping us diagnose diseases faster, treat them more precisely, and create personalized diet and exercise programs to prevent them in the first place.The book is now available in print and ebook formats. Just go to Amazon or Barnes & Noble and search for The Future You by Harry Glorikian.And now, back to the show.[musical interlude]Harry Glorikian: I mean, just looking at the system, there's probably a lot of innovations that were required to put Moxie together. And so. I don't know, maybe you can give us a few, you know, like "Oh, my God" moments that took place in this, right? I mean. I don't know if it's the physical movements. I don't know if it's the, you know, personality or the scripts. But, you know, give us the highlights of what you think was like the big breakthroughs that made this possible.Paolo Pirjanian: Yeah. So there are many, many, many, many pieces of technology that we had to invent or partner for to make this happen. So   what I mentioned, deep neural networks, generally speaking, in the field of AI have advanced to the point where we can have very reliable speech recognition technology, for instance, right? Where you have an accent or not, you're speaking loud or soft and so on, you have background noise and so on, it will be able to transcribe what you're saying pretty accurately. There are still errors, but it's pretty accurate. It's accurate enough, let's put it that way. The next stage of the conversation pipeline is actually understanding. Now you have a transcript of what was said. Now I need to understand the semantics of what was meant, what was the intent behind this, this string of characters, and that's natural language understanding. In that area, Embodied has made huge advancements because we have to be able to understand what the child is saying. And the state of the art when we started is defined by Siri and Alexa and Google Home, where it's very command and response. "Alexa, play music for me. Alexa, how is the weather? Alexa, tell me a joke. Alexa, read a story or read the news for me." And so on. So short utterances and and direct mapping to a function that the device can do. Whereas in our case it's not about this transactional command and response, it's about relation and social interaction. So the child, Moxie will actually ask and encourage the child. It says, "So how was your day to day?" There is no way any human being can script all the possible answers that you could expect to hear because you could basically say anything possible to that question.Paolo Pirjanian: So we had to develop natural language understanding that can understand what was said no matter what was said, and provide a relevant response. Because if you don't, if the robot says something that's absolutely not related to what the child wanted to talk about, then children get disappointed. They say, well, this thing is a dumb robot. It doesn't doesn't understand me. And they will dismiss it, right? The illusion of intelligence breaks away very quickly as soon as you you misunderstand or say something off script, let's say. So we had to develop a combination of systems to be able to address that. Another major challenge, and this was actually much bigger than I thought, we spent a lot of time on this challenge to solve. Again, it has to do with interaction using Alexa as an example also, and Siri as well as Google. They all have this notion of a wake word, Hey, Google, hey Siri or Alexa. When you say this keyword known as a wake word, the device is actually at the, when it's on standby, it's putting all of its attention to look for that keyword before it does anything else. So as soon as you say it, a couple of things happen. It's almost like turning on a switch to say, I'm going to speak, right? So number one, you're telling it, I'm going to say something now. Number two, as soon as you have said that phrase, these things have multiple microphones on them. And the mic array allows you to be able to be informed and focus your attention on the location from which you heard this phrase. With doing that, you can also filter out anything that's in the background. So you focus the attention of the device on that location of the user that said Alexa. And then you say a phrase and then it processes and executes the action. In our case, in social interaction, it will not be appropriate if you had to say Moxie in every volley of the conversation. Every time you want to say a sentence to me, you would start by saying Paolo and I and I would look at you, and then you would say something, and then I would stop listening. And then you say, Paolo, for every sentence, right. That would that would be a very awkward social interaction. So we had to solve that problem. It's a tough problem to solve. And we use a combination of cameras to know where the child is, the voice, where it's coming from, and what was being said to focus the attention of Moxie on the person that's engaged with it so that Moxie doesn't respond to the TV or mom and dad maybe having a conversation on the phone over there and it filters all of that automatically, without the need for having a wake word phrase. And I can go down the list. There is many, many more. But this is just examples of the type of things we have to solve.Harry Glorikian: So, you know, I think some people might make the argument that kids should really be learning their social and emotional skills from other human beings. From a parent, from a teacher, from their peers, maybe their therapist if they have one. You know, how can a robot fit into that picture in a healthy, productive way? You know, how would you respond to the potential criticism, which I'm sure you've heard before. When a parent who buys Moxie for their kid, are they offloading their parental responsibilities?Paolo Pirjanian: That's an absolutely valid concern and a good question to ask. And obviously, even before inception of the company, I personally myself was thinking about this because there is a there's a contradiction in saying that a child that is not very good at social interaction, let's put them in front of a robot, they'll get better at it. There's a contradictory element to that potentially. Right. So let's put it this way. In the extreme case, what if the child does not have the ability to have interaction with their peers? Right. So they do not get the opportunity to interact with other peers from which they're actually learning to hone in their social skills. Well, that happened during the pandemic. There's a huge mental health crisis happening in the US now that will take years for us to to address. That was because children were locked in their home without the ability to socialize with other children because of worries about being getting COVID, right. So now pandemics are rare events that hopefully don't happen that often. But now let's put ourselves in the shoes of children that are, for various reasons, are not successful in providing social interactions. An extreme case is a child on the autism spectrum. That does not have the right skills to have social interactions nor interpret social cues in a conversation. Let's say if you're annoyed at someone on the spectrum, it's likely that they may not even understand that you're annoyed at them and they may keep saying the same thing or doing the same thing. That's going to make you more and more agitated or the other end of the spectrum, which is not as severe.Paolo Pirjanian: My example when I was a child. And I lived in a foreign country where I was different. I had an accent. I looked different. I came from a different cultural background and other kids didn't want to play with me. And there's everything in between. Right? So then. What do we do? Well, you can have therapies and that's what we do. There's a massive shortage of therapists. If you have a child, usually the way this works is that your school teacher will come and say, we think your your child may be on the spectrum or your child may have ADHD or your child have some other neurodevelopmental challenge. You should get your child diagnosed. Okay. Hopefully no one has to try this. The waiting list for getting diagnosed is minimum six months, minimum six months. And that's if you have connections and good providers and all these things. While imagine for six months your mind as a parent, you're like, dying. What the hell is going on with my child? I've got to figure this out quickly. Once your child is diagnosed and you spend 6000, 7000 hours on that, then you've got to find providers. There's a huge shortage of providers, and even when you get to the provider, there is a massive cost associated with it. So typically children on the spectrum, as an example, get diagnosed at the age of three or so. Ideally, actually, because the sooner you can intervene, the better the outcomes. And when they're diagnosed, they will be recommended to seek 20 to 40 hours of therapy per week. 20 to 40 hours of therapy per week. Yeah.Harry Glorikian: They're not doing anything else.Paolo Pirjanian: No. And many times, many times schools are supposed to provide it. But you have one or two special needs teachers that are to deal with the whole population of kids on the spectrum in their school as an example. So they're not going to get 20, 40 hours per week. The cost of therapy is super expensive. Insurance also has to pay for it. Nowadays, they're mandated to, but the cost still adds up. On average, a family will spend $27,000 out of pocket per year, even despite insurance coverage. So not everyone has access. And also if you live in rural areas and so on, you don't have access. So. Why not have an automated system that can do this, at least filling the gap? Right. We think of Moxie as a springboard to the real world. So we want to use Moxie as an opportunity to for the child to open up to Moxie, use that as an option, teach them a number of techniques for how they can be more successful in social interactions, and then Moxie will actually encourage them to go in the real world and experience these things and come and tell it about what what, how it went. So we use Moxie as a springboard to the real world. There is another phenomena that happens, and I don't know how to describe this. You may actually have more insights in neuroscience than I do. Children, especially children that have neurodevelopmental challenges, open up to a robot like Moxie better than they do to humans.Paolo Pirjanian: Let's take autism as an example again. I remember the very first experiment we did with our first prototype. We took that prototype to a family's home. They had a ten year old son on the spectrum, and we put Moxie down. At the time we did not have the AI yet. It was the robot remotely controlled by one of our therapists. On an iPad they were typing what the robot should do and say. The child immediately opened up and start talking to Moxie. And if you look at that child, you say. And you know, as a matter of fact, I asked Mom: "I don't see anything wrong with your child. Why do you think he's on the spectrum?" And he says, well, you have to see him how he treats his peers. He doesn't open up to them. He doesn't want to talk to them. When he comes home from school it takes me, mom, a couple of hours to "find," quote unquote, my child. Tuning into the channel. So they shut down. And there's a few reasons for for sort of, I think, anecdotal or maybe rational reasons to why that is. One is that children that are on the spectrum, they completely understand feelings and emotions and so on. They are not very good at expressing themselves or or showing their feelings, but they understand if they are being rejected or teased out in a conversation and so on. So they shut down. A robot is non-judgmental, right? They understand that it's a safe, non-judgmental space.Paolo Pirjanian: The other part is that when someone like me who comes with a warmer blood and too many gestures and intonation, voice and expressive, it's too much there's too many signals going on. And that's overwhelming to a lot of children on the spectrum. And they shut down. It's too much. I cannot deal with this. Right. And so hence, a robot is finding social doing social exercises and experiences on training wheels. And helping them develop those muscles and get better at how to handle different situations when they go in the real world to interact with their peers or other people in their circle, social circle, to be successful. And that success will hopefully breeds more success. So ideally we are successful when people actually stop using our product. And as a matter of fact, we have parents reaching out to us and say, my child could not stand up in front of their classroom to say a word. Now she stands up and gives a whole presentation and we have stopped using Moxie. Thank you so much for the help that that's what what it is. It's like it's stepping stone. It's training wheels for social emotional learning so that they can have a chance of being successful, because otherwise they do not have the chance to to have these exercises to learn. We learn a lot by interacting with each other.Harry Glorikian: So the company describes Moxie as just the first iteration of a larger platform that I think you call SocialX. So what is SocialX and what other kinds of products do you envision coming out of it?Paolo Pirjanian: Yes. SocialX is our technology platform, which which allows a machine to interact with us using real conversation, eye contact, body language, gestures, intonation of voice and and for the machine to do that as well as understand you on all those channels as well. That's what social platform is. The name SocialX is a juxtaposition to user experience, UX with an emphasis on the social experience. Right? We are creating a social experience. We are not just creating a user experience where you can push buttons or say a command, play music. Tell me the weather, what's the stock market like? But rather social interaction which involves social skills, emotion, skills, empathy and so on. And this is our first iteration. It's going to get exponentially more advanced. With every single user we add to our customer base, it allows us to improve SocialX because the data and the interactions that we can experience allows us to keep improving our algorithms to get better and better and better. So we decided to start with children because they are the most vulnerable in our society and we thought that's where we can have the most impact. The other end of the spectrum, where we become vulnerable again is when we are aging, right? And mental health is extremely important for aging people. And loneliness leads to a lot of mental health challenges that lead to a lot of physical challenges.Paolo Pirjanian: We know this. The surgeon general of U.S. said a couple of years ago that loneliness for elderly is equivalent to smoking a pack of cigarettes in terms of the health implications it has. And it's true. Again, during COVID, a lot of elderly that were alone suffered massively because they were high risk for COVID. Even my mom, who lives 5 minutes away from me, I didn't visit her for a few months until we sort of figured out that we think we know how to handle COVID so it was safe to to meet meet each other. It's extremely difficult. So that's the other end of the spectrum that we intend to address. And then in between every age group, in between that, from your teens to your aging, every person in their lifetime deals with mental health challenges. As a matter of fact, the US population, 17 percent of the population at any given time deals with mental health challenges stress, depression, suicidal thoughts and so on. And having a life coach that can help you through these difficult times, we believe can have a huge impact. So eventually with those three pillars, we will be able to help the entire population. You can go beyond mental health, which is what we are focused on, because that's where we think we can have the biggest impact you could imagine.Paolo Pirjanian: You go to Disney Park and you could have an interactive character coming up to you that's not a person inside a suit, but it's actually an animated character that's walking around and talking to you and entertaining you. You can imagine going to a hotel lobby where your intake to the lobby will be serviced by an interactive character, AI character. By the way, we are also working with hospitals and schools. Right now for hospitals we work with University of Rochester Medical Center. We are currently doing a pilot of using Moxie to help children, diabetic children, to educate them about how to treat themselves and how to adhere to their treatment plan. And then there is a number of other use cases that we are going to expand into, including intake to the hospital, dealing, sort of holding their hands and making sure they are not stressed out, coming to the hospital for the first time, pre-op and then post-op. Also a lot of complications you want to avoid by making sure there is someone to remind you about your care plan and so on. So to be honest with you, the sky is the limit. But the three areas we are focused on is children, elderly and then everyone in between that suffers from mental health or loneliness type of challenges.Harry Glorikian: Yeah, there are so many other applications that I can think of that I would, you know that I could use my self. So hopefully, that will come into play because this would be something interesting for me even to interact with, depending on, you know - Don't forget to work out or, you know, there's something that you interact with regularly. Right. But so let's go to sort of the crux of the some of the issues. Right. It's it's not an inexpensive device. I mean, it does a lot. So you can't expect that it's going to be inexpensive. Right. It's it's $999 to purchase plus a separate monthly subscription of about, what is it, $39 per month for a minimum of 12 months. And so how how do you get this out to a larger group of people that really need it. Is it subsidized purchases? Is it insurance? What are you guys thinking of from a business model perspective?Paolo Pirjanian: Yes. So we actually launched the product in the second half of last year for the first time and we sold out. But I agree with you that it would be much better if it was more affordable, because we don't want this to only be a product available for high income families, for rich kids to use a derogatory term maybe. We want it to be available to every every child. And for that to happen, there is a couple of different strategies we are pursuing. One is that once we get to a scale of efficacy studies that are convincing enough that we can get insurance, potentially insurance coverage to cover it or at least subsidize part of it to make it more affordable. The other approach is that we are working with bigger institutions such as hospitals and schools and libraries, by the way, which can buy it and make it available to their population. As an example, this library actually came to us, which is a very interesting business model that addresses the reach to the society that may not be high income. The library bought a fleet of Moxies from us, and they're lending them out to their society, to their members as a book. So a child gets to take Moxie home for a month and then bring it back, which is awesome because we have, by the way, we have done efficacy studies and it shows that even within a month you can see significant improvement on a lot of these social emotional skills.Paolo Pirjanian: But ultimately, that's that's how it goes. And also, just to put it in perspective to two examples. One is that robots of this nature....By the way, there is nothing like Moxie because the technology has not existed today, but people have tried, actually, SoftBank has a subsidiary called SoftBank Robotics that have spent hundreds of millions of dollars developing this robot called Pepper that costs $14,000 to buy and $2,000 a month to subscribe to it. Yeah. So we are orders of magnitude better than that. And that was part of the design principle that we said we want to be on par with an iPhone ownership of a cell phone. Buy it for roughly about $1,000. And you pay roughly about $50 a month in subscription. So we met that goal, which was a major accomplishment, very hard to do, but we are not satisfied with that because as I said, this has to be available. The other part of the other example is that if you have a child that needs therapy and if this cuts your therapy by a handful of therapy sessions, it pays for itself. Right? Again, ideally, we will have insurance pay for it. And so that will take some time. As you know, sort of navigating the medical fields and insurance organizations and so on will take some time, but we will get there eventually.Harry Glorikian: Yeah, I mean, I recently interviewed the CEO of Akili Interactive, Eddie Martucci, and they are the first group to get an FDA approved prescribed video game for children between eight and 12 years old with certain type of ADHD. And so, you know, they're using the prescription route as a way to have somebody pay for the clinical trials and everything else and the product itself. So I know that this business of robotics is not for the faint of heart. I mean, there's there's many different companies out there like Jibo, which was out here. Or I think there was a company in in San Francisco called Anki that, you know. You didn't pick an easy one, that's for sure, Paolo.Paolo Pirjanian: Definitely not. Definitely not.Harry Glorikian: But but, you know, I you know, I wish you incredible luck. I mean, this this thing sounds so exciting. I mean, it brings out, like, the Star Trekkie guy in me and wants to interact with it and have it do certain things or say certain things or or maybe even like interact with my wearable and be able to see something and then make a comment to me as I'm using it. So I can only wish you incredible luck and success.Paolo Pirjanian: Thank you. I need it and I appreciate it.Harry Glorikian: Excellent. We'll talk soon.Paolo Pirjanian: Talk soon, thank you so much for having me.Harry Glorikian: That's it for this week's episode. You can find a full transcript of this episode as well as the full archive of episodes of The Harry Glorikian Show and MoneyBall Medicine at our website. Just go to glorikian.com and click on the tab Podcasts.I'd like to thank our listeners for boosting The Harry Glorikian Show into the top three percent of global podcasts.If you want to be sure to get every new episode of the show automatically, be sure to open Apple Podcasts or your favorite podcast player and hit follow or subscribe. Don't forget to leave us a rating and review on Apple Podcasts. And we always love to hear from listeners on Twitter, where you can find me at hglorikian.Thanks for listening, stay healthy, and be sure to tune in two weeks from now for our next interview.

When you hear artificial intelligence (AI) and big data it may be robots, smart homes and self-driving cars that you think of, not necessarily your health. AI and data have a powerful role to play in our health with potential applications that will change the face of health care. This week's guest, Harry Glorikian, AI expert, healthcare entrepreneur and author enlightens us about the fascinating technological innovations taking place in the health care space.Harry is the author of, The Future You: How Artificial Intelligence Can Help You Get Healthier, Stress Less and Live Longer. Most of us what those things and according to Harry, judicious use of AI can help us achieve them.We talk about the ability of AI to analyse and synthesise enormous amounts of data and the implications of this. Applications most of us are already aware of and using are things like smart watches, activity trackers and devices that measure sleep metrics. Going forward we will be able to have personalised nutrition advice based on our genome and decentralised health care where we can use a portable X-ray at home and be advised whether we need to attend the ER department or not. AI opens the door to significant improvements in cancer treatments where the genomic sequence of a cancer tumour can be used to determine the best treatment protocol rather than relying on trial and error.AI played a significant role in diagnosing and detecting the SARS-CoV-2 virus and developing effective vaccines in record time. Harry explains how this was achieved with the help of AI and how, because data can be processed so quickly in a short space of time, procedures that would previously have taken years took weeks to months. Vaccines were developed quickly but not because corners were cut. It is fascinating to understand more about this.Tune in and learn about our future!HARRY GLORIKIAN & LINKS MENTIONEDHarry Glorikian: https://glorikian.comThe Future You: https://glorikian.com/the-future-you/Harry's social media handle @harryglorikianKardiaMobile EKG: https://store.kardia.comWHOOP band: https://www.whoop.com/en-au/Eight Sleep: https://www.eightsleep.comHOW YOU CAN SUPPORT THE PODCASTPlease tell your friends about the podcast and share it with them.Follow me on Instagram @vibrant_lives_podcastFollow my Facebook page: @vibrantlivespodcastIf you could rate and review the podcast on Apple Podcasts, that would be super helpful.Check out ways you can support the podcast on my website: https://vibrantlivespodcast.com/be-involved/

Knowledge Bomb: Dr. G goes into what is reducing our sex drive. Why are so many of us suffering with low libido? What does a low libido mean? What are the root causes of a poor sex drive? How do we address the physical, mental/emotional causes? Sexual health is essential for healing thy self. Special Guest Segment: Jeff Chilton, a world renowned Mushroom expert gives us the low down on the industry: How corrupt is the mushroom industry? What are the signs of a poor quality mushroom product? What do we have to look for when buying a quality mushroom product? He also tells us about which mushroom is the most powerful one of all! Super informative as the mushroom boom is arriving, we must know how to navigate this space. GUEST BIO: Jeff Chilton studied Ethno-mycology at the University of Washington in the late sixties and in 1973 began a 10 year career as a large scale commercial mushroom grower. Jeff is the co-author of The Mushroom Cultivator, published in 1983. In 1989 Jeff established Nammex, the first company to supply medicinal mushroom extracts to the Nutritional Supplement industry. In 1997 he organized the first organic certification workshop for mushroom production in China. Jeff is a founding member of the World Society for Mushroom Biology and Mushroom Products in 1994 and a Member of the International Society for Mushroom Science. Nammex extracts are used by many supplement and food companies and are noted for their high quality based on scientific analysis of the active compounds. ADS: It's Four Sigmatic's birthday! In honor of their day Four Sigmatic is offering 50% off membership subscriptions. This is their membership program where there is no fee to join, no strings attached, the ability to cancel anytime, and SO many perks. Subscriptions are a standard 20% off all products plus free shipping, an exclusive community, and early access to all new product launches. Later this year, we will also be releasing our first subscription only products! Now is the perfect time to join for half off some of the best products out there. You can also use code DrG for 20% off all orders on FourSigmatic.com. I love my Birch mattress, and I think you would too. If you're looking for a new bed, check out Birch. You can click the link below or go to birchliving.com/healthyself and get $400 off your mattress + two free pillows Be sure to like and subscribe to #HealThySelf Hosted by Doctor Christian Gonzalez N.D. Follow Doctor G on Instagram @doctor.gonzalez https://www.instagram.com/doctor.gonzalez/

Is kindness the fountain of youth? Join The Art of Kindness podcast as we explore a new study published in the journal Frontiers in Behavioral Neuroscience and more in a special bonus episode! Got kindness tips or stories? Please email us: artofkindnesspodcast@gmail.com Follow us: @artofkindnesspod / @robpeterpaul Support the show! (https://www.buymeacoffee.com/theaok) Learn more about your ad choices. Visit megaphone.fm/adchoices

Are you wondering how you can live a longer, more fulfilling life? Many of us resort to external means, like testosterone replacement therapy, in hopes of achieving this. What we fail to realize is that with a little discipline, we work to can extend our lives ourselves. In this episode of The Mentee Podcast, Howard Aaron shares his tips, tricks, and knowledge on how to extend your life by simply maintaining an active lifestyle. You'd never be able to tell he's turning 70 — what's stopping you from being the same? Howard also talks about blocking out the “noise between your ears” and how, by doing this, you can achieve so much more. Here are some power takeaways from today's conversation: Exercise is important, but rest and recovery are just as crucial to increasing testosterone levels By blocking out the “noise between your ears”, you can allow yourself to reach higher heights There are many natural alternatives to testosterone replacement therapy available Consistency trumps infrequent activities that only bring mental satisfaction [4:47] Howard's Stance in the Testosterone Replacement Therapy Debate Howard was invited to take part in a debate about the benefits of testosterone replacement therapy. He shared that he doesn't use it and argued that we don't need it as there are many natural alternatives to testosterone replacement therapy available.  Howard went on to form a group and start a program to encourage men to look into increasing testosterone levels through exercise. [17:03] Blocking Out the Noise Between Your Ears Our id, ego, and superego all play separate roles and tell us different things, many times talking us out of opportunities even before they arise. By learning about and understanding them, we can work against them. [33:50] The Top Three Natural Ways to Boost Your Testosterone Levels  Howard shares his top three ways to naturally boost your testosterone levels: Proper resistance training Eating clean Getting good sleep Listen to the full episode to hear Wyatt and Howard's deep dive into this topic! [47:56] Keeping a Consistent, Active Lifestyle New trends are always popping up, but there will never be a perfect, singular way to live out your active lifestyle. Rather than chasing after mental satisfaction, stay consistent — your whole body will feel much better for it. Resources Mentioned: https://www.howardaaron.com/ (https://www.howardaaron.com/) Howard's book, Strength Training For Life: Your Journey to Live Longer and Stronger Call Howard at 484-919-2700 Email Howard at ocibois@gmail.com

On this episode we'll be finding out about a new way to take charge of your own happiness and health. Our guest, Dr. Kelli Harding, says love, friendship, community, purpose and our environment can have a far greater impact on our health than anything that happens in the doctor's office.    Dr. Harding is a Columbia University-trained, board certified psychiatrist who specializes in the interplay between mental and physical health. She's the author of the book, THE RABBIT EFFECT: Live Longer, Happier, and Healthier with the Groundbreaking Science of Kindness. Thanks to our sponsors of this episode! --> AirMedCare Network: AirMedCare Network provides air ambulance services in the event of an emergency. Iif you're a member, you'll pay no out of pocket costs for the flight when transported by an AMCN provider. Were you aware that health insurance doesn't always cover the full cost of emergency air transport? AMCN Membership is financial protection for your entire household at an affordable price. Right now, AMCN is offering our listeners the chance to win 10,000 dollars and backyard prizes like a Blackstone griddle, a Solo Yukon firepit, an outdoor theater kit, and 100 dollar Costco gift card with their Summer Sizzle Sweepstakes. No purchase necessary to enter– but if you do decide to purchase a membership during this special promotion, all AMCN members will receive up to 200 bonus entries for their chances to win great prizes. Head to airmedcarenetwork.com before May 13 and enter your information. --> Athletic Greens: Athletic Green's AG One is a special blend of ingredients that supports your gut health, nervous system, immune system, energy recovery, focus and aging. In just one delicious scoop of Athletic Greens mixed with a glass of water, you're absorbing 75 high-quality vitamins, minerals, whole-food sourced superfoods, probiotics, and adaptogens. Athletic Greens uses the best products based on the latest science with constant product iterations. Right now, it's time to reclaim your health and arm your immune system with convenient daily nutrition, especially in the flu and cold season. Athletic greens is going to give you a free one year supply of immune supporting vitamin D and five free travel packs with your first purchase. All you have to do is visit athleticgreens.com/ntm. Learn more about your ad choices. Visit megaphone.fm/adchoices

Kyle And Jackie O Open, My Child Will Be Named Megatron, Headlines True or False, Man signs girlfriend up for etiquette class, Do Oscar Winners Live Longer, Have You Eaten These Following Southern Foods, Yes, Machine Gun Kelly & Megan Fox. More at www.CooperandAnthony.com

I attended a biohacking conference with Dave Asprey, the "Father of Biohacking" and founder of Bulletproof. And I am obsessed with this topic. David Sinclair of Harvard and Andrew Huberman of Stanford are two fantastic resources on this subject. Are you a biohacker? Biohacking is the art and science of changing your environment and biology to be a high performer. In this episode, I will talk about 6 HIGH-PERFORMANCE HABITS so that you can PERFORM BETTER, AGE IN REVERSE, LIVE LONGER and LOSE WEIGHT. Tune in today!

 Well as we challenged you yesterday with the thought that it may not be how long you live but how you live are you doing what matters with your life.  But living long and living healthy is a very good idea. So can I share with you a new interesting idea from a new book that just came out, and indeed some of the foods that might help you just live longer, and most important, healthier.  And remember eat your broccoli.

Population and Development Review published a study 'Large and persistent life expectancy disparities among India's social groups' talking about life expectancy of different social groups in India. In Episode 989 of Cut The Clutter, Shekhar Gupta reads into the study and analyses the complex data to understand if caste, religion or ethnicity actually determine life expectancy in the 21st century.

We all want to live longer, healthier lives — and if we can get younger while doing it, well then, all the better! In this episode, Dr. Kara Fitzgerald joins host Paula Felps to talk about her new book, Younger You: Reduce Your Bio Age and Live Longer, Better. Kara is one of the leading voices in the intersection of nutrition, epigenetics and aging, and she's here to talk about what her research says about how to not just become healthier, but to actually reduce our biological age from the inside out.   In this episode, you'll learn: The difference between genetics and epigenetics — and how each one affects your health. What nutrients can help slow aging and improve your health. How exercise suppresses tumors — and why it becomes more valuable as you age.

Can a video game help improve attention skills in kids with ADHD? According to Akili Interactive in Boston, the answer is yes. They've created an action game called EndeavorRx that runs on a tablet and uses adaptive AI  to help improve focus, attentional control, and multitasking skills in kids aged 8 to 12. And it's not just Akili saying that: In 2020 the U.S. Food and Drug Administration agrees cleared EndeavorRx as a prescription treatment for ADHD, based on positive data from a randomized, controlled study of more than 600 children with the disorder. It was the first video game ever approved as a prescription treatment for any medical problem, and Harry's guest this week, Akili co-founder and CEO Eddie Martucci, says  it opens the way for a new wave of so-called digital therapeutics. Even as Akili works to tell the world about EndeavorRx and get more doctors to prescribe the game for kids with ADHD (and more insurance companies to pay for it), it's testing whether its approach can help to treat other forms of cognitive dysfunction, including depression, the cognitive side effects of multiple sclerosis, and even Covid-19 brain fog.Please rate and review The Harry Glorikian Show on Apple Podcasts! Here's how to do that from an iPhone, iPad, or iPod touch:1. Open the Podcasts app on your iPhone, iPad, or Mac. 2. Navigate to The Harry Glorikian Show podcast. You can find it by searching for it or selecting it from your library. Just note that you'll have to go to the series page which shows all the episodes, not just the page for a single episode.3. Scroll down to find the subhead titled "Ratings & Reviews."4. Under one of the highlighted reviews, select "Write a Review."5. Next, select a star rating at the top — you have the option of choosing between one and five stars. 6. Using the text box at the top, write a title for your review. Then, in the lower text box, write your review. Your review can be up to 300 words long.7. Once you've finished, select "Send" or "Save" in the top-right corner. 8. If you've never left a podcast review before, enter a nickname. Your nickname will be displayed next to any reviews you leave from here on out. 9. After selecting a nickname, tap OK. Your review may not be immediately visible.That's it! Thanks so much.TranscriptHarry Glorikian: Hello. I'm Harry Glorikian, and this is The Harry Glorikian Show, where we explore how technology is changing everything we know about healthcare.Can a video game help improve attention skills in kids with ADHD?According to Akili Interactive in Boston, the answer is yes. They've created an action game called EndeavorRx that runs on a tablet and uses adaptive AI  to help improve focus, attentional control, and multitasking skills in kids aged 8 to 12.And it's not just Akili saying that.The U.S. Food and Drug Administration agrees.In 2020 the FDA cleared EndeavorRx as a prescription treatment for ADHD, based on positive data from a randomized, controlled study of more than 600 children with the disorder. It's the first video game ever approved as a prescription treatment for any medical problem.Kids are advised to play the game for 25 minutes a day, five days a week. After two months of play, two-thirds of parents of kids in the controlled study said they saw a meaningful change in their children's day-to-day impairments. The FDA's approval of EndeavorRx opens the way for a new wave of so-called digital therapeutics, designed to treat all kinds of problems with cognitive functioning, including depression, the cognitive side effects of multiple sclerosis, and even Covid-19 brain fog.Akili is busy telling the world about EndeavorRx and working to get more doctors to prescribe the game for kids with ADHD and more insurance companies to pay for it. And here today to tell us about all of that is Akili's co-founder and CEO Eddie Martucci.Harry Glorikian: Eddie, welcome to the show.Eddie Martucci: Thanks, Harry.Harry Glorikian: So I'm dying to get into the company and all the things you guys are doing. But, like, before we jump into the company, I'd love our audience to get to know you a little bit. Right, because you're a long time health entrepreneur. You got your PhD at Yale in the departments of pharmacology and molecular biophysics and biochemistry, where you studied structure based drug design. But how did your personal path lead you from molecular biology, which is near and dear to my heart, to video games to treat cognitive impairment? I mean, that that's not exactly the Venn diagram I would see that somebody would just put together.Eddie Martucci: No, it's not. And there is no there is no path for this. Right. Because this is so different and so new. I would say my personal passion is just new science findings. Like I just love brand new science. I was a researcher for a short stint while I did a PhD. I think I had some pretty cool research. But really, if I zoom back, it's new science and new discoveries that are moving the health world forward. And that can be whether it's insights about some part of our biology that we didn't know before, that leads us to understand the human body better. Or in the case of what I've really done from a professional perspective, it's scientific insights that can lead to new treatment modalities. And so that's really what got me most excited. I think the path that was most impactful for me, you know, I was a biochemist at Providence College and a biochemist and biophysicist at Yale, and I love proteins and structural biology and all that. I still do. But I came out of my PhD and and worked with a group called PureTech Health in Boston. And Puretech is really just this unique new health care company where they've done everything from, they have research and development and discovery, but they also have in many ways nailed down a process of starting new companies off of groundbreaking science. And so while I was in grad school, I was exposed to a couple entrepreneurs that really put a light bulb in my head that, wow, this is something I should look into. And then I got training at PureTech in Boston. And that's what kind of got me thinking about brand new medicine and brand new modalities that were never considered medicine before. And the rest is history. Once you get a framework where you can start thinking like that, then it's just work.Harry Glorikian: Yeah. I mean, I knew Daphne, I think when she started PureTech and her advisory board was like, I mean, Nobel Prize winning, who's who sort of. Right. Just watched it evolve over time. But, you know, when you were at PureTech, I think one of their focuses was neurophysiological disorders. I mean, is that the real bridge that helped start Akili? Because I remember that came out of Adam Gazzaley's lab at UCSF, if I remember correctly.Eddie Martucci: Yeah. Adam Gazzaley is where we found the core technology that which we call SSME, which has gone on to power our products, including our FDA approved product. But yes, what I was working on at PureTech, including directly with Daphne, who's really brilliant in helping and bringing new big ideas to life and board members, including people like Ben Shapiro, who used to be at Merck. And he was one of my longest term board members. It doesn't hurt to have folks like Bob Langer in the room once every quarter to bounce ideas off of as well. So like, a very privileged place to start a company. But yes, I was working on novel CNS technologies, in fact. In fact I was working on a few and one in particular that was new devices, new devices for various neurological conditions. And it was really from that effort in thinking about what are the newest modalities of medical devices that we leaped one big bridge further and said in 2010 or about or maybe 2009, could we go further from a user experience perspective now that the whole world is carrying cell phones and tablets every day? Could we go further? Could we could we think about digital? And that was right around the time when everyone and their mother was talking about digital helping medicine. And because we were in the headspace of novel therapeutic modalities, I think it was a natural leap to say, what about digital being the medicine? And then we had to find the science. And that's where I found Adam Gazzaley and, and, and we got off to the races with that technology from UCSF.Harry Glorikian: Yeah. I mean this whole area of digital therapeutics, I've been talking about it for years now and trying to convince people and they look at me really weird when I say digital therapeutics and I try to explain it to them. But so but the game you have built is called EndeavorRx. If I got that correctly. And can you tell? Me more about the game itself. Like, what are the operative features or game mechanics that are thought to increase attention in kids who play the game?Eddie Martucci: You kind of have to back up to the core technology. So the way we build the business is not building one product or one game. We're building a platform technology, meaning a technology that is not made for a single disorder. But instead the problem we're going after and that we started with all of those years ago, about a decade ago, is cognitive functioning. Cognitive dysfunction in medicine is not targeted well by molecular pharmacology. That is the problem statement. We don't target cognition very well in medicine, if at all. And so our whole theory and thesis for the business was, if we could bring in the best technologies in the world, that through software could actually target cognitive functioning directly, then we would be bringing a pillar of medicine that does something much, much different than what medicine does today. So the technology out of UCSF that we started the company around, that we have branded the Selective Stimulus Management Engine, the way this technology works, which will then help you understand how the products in for ADHD children works. The way this technology works is it is giving constant stimulus, both visual and motor. So it's creating conflicting and overwhelming stimulus to activate the part of the brain that controls attention, which is the midline prefrontal cortex. So the front part of the brain that really controls attention and speed of processing and integration, this technology is patented to be able to activate that part of the brain very strongly, but also enhance what's called long range coherence. So as you're using this technology, not only is the front part of the brain activating much more, so you can apply your attention downwards.Eddie Martucci: And I'll get to exactly how this manifests, I promise. It is also more seamlessly based on the neurological data we have. It appears to more seamlessly be helping the brain communicate to the sensory processing regions. And so the way this manifests in ADHD children, when they're using our product EndeavorRx, which is meant for children 8 to 12 years old with ADHD who struggle with the attentional issues. This product is basically experienced like a racing video game where children are running a little alien figure down a course that is ever adapting. And they're getting information, meaning things that fly up to the screen that they have to make decisions on. And that's ever adapting because we have these deep, personalized algorithms so that everyone gets their own experience. So basically what people feel is they're using this technology that feels like a game, and it's just constantly challenging them in different ways. What's happening in the brain and this is how it's designed, is that the game is presenting very specific stimuli for each user that is pushing them at the edge of their processing ability. And that's part of the IP we have, is how to do that in a really seamless way so that by the end of using a game you haven't just been using a game, you have been essentially taxing the weak link in your attentional processing every single second for hours.Harry Glorikian: I think every CEO of that we may know mutually needs to be prescribed this game.Eddie Martucci: You know, CEOs and investors have been probably the most common people that in meetings will stop me and say, hey, I think I need this.Harry Glorikian: Yes. So how did you ideate and test the game mechanics?Eddie Martucci: Yeah. This is this is really a tenet of the business where we decided early on that to truly—we want to disrupt medicine and we want to create and integrate our type of medicine into mainstream medicine. Far too often, digital is kind of left to early adopters or on the sidelines of real medicine, excuse me. And our whole thesis was you have to run real validated and literally gold standard, rigorous clinical research. So when we had done this, no one had done a well designed trial before to study something that looks like a video game. And so that's really where we spent the first handful of years of our existence is after we built the kind of data infrastructure, which we can talk about, and the adaptive algorithms. We then invested years in how to run good clinical trials with this type of product that's an experiential product. So our goal all along was being able to run the same or better rigor of randomized controlled trials that you'd expect from a drug for this same disease area. Obviously, as an interactive product that you can see and you interact with, that means you have to take a little bit of a different approach.Eddie Martucci: So we had to do a lot of work with some of our advisors and with places like Duke University on how to blind the protocol. Because it has to blind very differently. And how to how to have a control, an active controller sham that is actually controlled. And there's many nuances like that. But at the end of the day, the trials we run are meant to replicate or be analogous to drug trials, where you have really strong controls up front, that you're not biasing individuals and that the outcomes—and this is the differentiator in digital—that the outcomes are gold standard accepted outcomes for whatever you're studying. And so that was what we've done. What we did the first time we were in a trial, we were like, it took a lot of work and we were nervous about it. But we have a clinical ops team now and we've run a few dozen trials across, I think, nine or ten disease populations, so we've become pretty good at it.Harry Glorikian: Yeah, I was going to say, I mean, coming up with the first one, everybody's probably scratching their head trying to figure out, are we doing the right thing? But, and I have this discussion with some of the people I work with all the time, what's the proprietary special sauce in the case of digital therapy? I mean, is there a defensible algorithm or insight at the heart of something like EndeavorRx that would be comparable to a patented small molecule in the you know, in the traditional drug industry?Eddie Martucci: In our case, yes. And I'll tell you about that. I think what this really comes down to, though, that question about digital therapeutics, it's like a business question for the industry. To answer that question, it's important to recognize there's nuance in the industry. So the vast majority of digital approaches, I think, are tough to protect because they're taking well known human practices and putting them into an app. Right. So there's 90 percent of the digital therapy companies or products out there are using different forms of behavioral therapy or disease management techniques or strategies, and they're bringing them into an app that is not bad. It's hopefully very, very good for patients. There's a few validated products there that are, no question, good for patients. I think it does make those types of products harder to protect. We've taken a bit of a different tack. We're a little bit, I guess, iconoclastic within the industry in that what gets us excited is software that even though it's software, it's more drug like in that it's directly targeting and activating the dysfunctional physiology in the body. You can measure that and by virtue of that, you're having a really unique effect. Eddie Martucci: The second big difference is we are using algorithms that have not been ever reported on before. So we take much more of a drug lens where we actually do protect we patent our technology. So we call this whole class “physiologically activating digital therapeutics.” Some people have referred to them as mechanistic digital therapeutics or disease modifying. There's different phrases, but this idea of unique algorithms that you actually can protect with patents and copyrights, which we do. So we have about 50 issued patents for the technology that underlies EndeavorRx and another 100 that are filed on our various technologies. And you can demonstrate this has a real, unique physiological effect. I think what it enables, at least for these types of products is a feeling from the health care world that this is much more what I'm used to seeing in my traditional medicine where it's unique. I can't just go get this anywhere because I trust that this one product is the only one that has this unique technology. And by the way, it's been proven to work. And I trust that they're a stable company that's going to be around for a while. Those things are really important to our model.Harry Glorikian: Well, it's a good thing that I've been explaining it to people the right way. So at least now that we've talked, you know, my explanation is aligning correctly. So I'm happy about what I'm reading is correct. Let's take a step back. So, there's a lot of kids with ADHD who have no problems concentrating on something for hours if they're really interested in it. But it strikes me the key feature of the of the product is not just keeping kids engaged. It's supposed to build or improve those skills. Is that the key thing that makes the game special or unusual or different from any other pastime, say, building LEGO spaceships?Eddie Martucci: Yes, absolutely. So the engagement is critical, but the differentiator is the challenging and improving of that core cognitive functioning. And you don't get that just by engaging in something. And actually, the vast majority of entertainment products you engage with will allow you to either passively engage, meaning you could watch YouTube videos for hours and hours, but you're not actually challenging your brain or actively engage, but in a way that you don't really have to challenge what you don't do well. So in most video games, you can choose what most of us do in life, choose the path of least resistance, because we like certain ways of using a product. Our product is unique in that this this patented algorithm forces you—it's essentially measuring second by second where you're weak and processing the various streams of information and it is forcing you to work on those areas where you are weakest. But it's doing it naturalistically. It feels like you're using a treatment, but it's really that level of focus on, for lack of a better word, it's really that level of focus of delivery of that algorithm that's actually going to stress you where it, for lack of a better word, hurts the most. That is the differentiator. The other big differentiator is, is the personalized algorithms that that we built in. And this is where, frankly, technology and data rich medicine has never gone before. But within seconds of using the experience, this product is tailoring to each individual user. And this is true whether we're talking about kids with ADHD or some of our trials and products and adults with depression or MS, these products can actually tailor to your functional level and then move you along from there. So those two those two bits of how the algorithm works are critically important. The engagement is really the delivery vehicle to make sure you're getting that level of medicine.Harry Glorikian: Yeah, definitely, if this was available to people in a larger age range, there are people that I definitely need to recommend this to when well then that becomes available.Eddie Martucci: But well, that's the interesting thing about cognitive dysfunction, right? The way I talk about it sometimes is cognitive functioning and or problems with cognitive functioning go across disease, right? They're in many ways disease agnostic. Almost anything that touches the brain results in some level of cognitive dysfunction or at least some proportion of patients that have longer term cognitive dysfunction. But it also goes above and below disease, meaning subclinical. So there are people that are not diagnosed with issues that, you know, that probability-wise there's 20 or 30 percent that are significantly below the mean they're struggling with these things. So this is a this is a basic human function that rears its head in a really nasty way in many diseases, but is actually relatable to all of us.Harry Glorikian: Yeah. So. I mean, there's a lot of challenges when you're trying to design something like this. A ten year old will not spend much time playing a mobile game unless it's it's just as compelling as, you know, anything that they could download as a mobile app. So. How did you guys, what steps did you guys take? You know, it's almost like game design and, you know, therapeutic outcome, you know, together in one package. And so how did you guys, what steps did you guys take to make sure this thing was fun?Eddie Martucci: Correct. Yeah. And it does depend on the population. Right. So we have products, obviously a marketed product in for children with ADHD, but we're developing products and have trials and data and adults of various ages. The I think you're right. If you focus on children, there's a there's an engagement bar that is not easy. Right. Kids are highly discerning. They know a good game and a bad game. And what we like to say is we have no delusions that we're going to come out with the next blockbuster entertainment game. That is not how we built the company. However, we do want to have a game that looks and feels like the type of games that you actually like to play. So it has to be worlds better than edutainment, as people call it, educational software, because kids know. And so the way we did that is this is one thing that makes Akili very unique. Instead of outsourcing or kind of outsourcing game development or adding game development at the end of our development cycle, we actually have built the company to have cognitive science, clinical science, and game development fully integrated from the earliest days. And data science, for what it's worth, is really a kind of foundational thread for all of those. And it's hard. It's really hard. I mean, developing a product that has both these things, the strong science and the engagement, is really hard, but it's also really hard for people from all these different industries to, you know, be speaking the same language and work together because the development processes are different, the language you use is different. Your mindset of how you think about developing is different. And so for us, what I always talk about is it's literally daily attention. I'm unwilling to sacrifice or give up on it. We have to do both. Well, I think where we are today with EndeavorRx as our first product out of the platform, it's a really good product. It was built to show clinical efficacy and engage people to a minimal degree. It does that. Some kids love it. They will play for months at a time, you know, five days a week for four months. But yeah, there's a lot of people that kind of get through it and then plenty of kids that say, I really don't want to use this. So we've built features around the edges, things like an app for parents to allow them to track and monitor and incentivize their children. And we try to educate our users on why you're doing this. And so it's got to be a mix of the engagement itself, but also a little bit of inherent motivation that, hey, your doctor's in the loop, this is your medicine. It's important to put the work in and accomplish it.[musical interlude]Harry Glorikian: Let's pause the conversation for a minute to talk about one small but important thing you can do, to help keep the podcast going. And that's leave a rating and a review for the show on Apple Podcasts.All you have to do is open the Apple Podcasts app on your smartphone, search for The Harry Glorikian Show, and scroll down to the Ratings & Reviews section. Tap the stars to rate the show, and then tap the link that says Write a Review to leave your comments. It'll only take a minute, but you'll be doing a lot to help other listeners discover the show.And one more thing. If you like the interviews we do here on the show I know you'll like my new book, The Future You: How Artificial Intelligence Can Help You Get Healthier, Stress Less, and Live Longer.It's a friendly and accessible tour of all the ways today's information technologies are helping us diagnose diseases faster, treat them more precisely, and create personalized diet and exercise programs to prevent them in the first place.The book is now available in print and ebook formats. Just go to Amazon or Barnes & Noble and search for The Future You by Harry Glorikian.And now, back to the show.[musical interlude]Harry Glorikian: What makes you optimistic? Because I've been, you know, enamored with this space for a while now and trying to watch like where it's going to grow and what's going to get in its way. And so what makes you optimistic about digital therapeutics, either as a venture scale business or a public company. Because I know you guys are thinking about that. Tell me what you're thinking.Eddie Martucci: Yeah, a couple of things that make me very optimistic. I think the foundational groundwork is now done and we've shown it can be done. So we know that these products now can be developed, they can be protected, they can be brought through clinical trials and actually help patients. That's the most important thing. They can undeniably with strong clinical data, help patients and they can be brought through the FDA and now being prescribed by docs. So these prescription digital therapeutics, there's only a couple of them on the market. But literally at this point there's been now thousands of docs, not merely tens or hundreds, but we're talking now about thousands of docs who have prescribed prescription digital therapeutics to patients, where a couple of years ago that would have been essentially zero. So the foundations are there more. Every month that goes on, it becomes a a self-fulfilling cycle where doctors and patients hear about it, they're aware of it. They know someone who's tried it. And it's becoming a little bit common nature to think, wait, isn't there something digital that I've heard about for this? I think that will flip in the coming years to I expect to have a digital treatment or I expect to be told the digital option for my doc. So that makes me that makes me optimistic is that the groundwork is there. We know it can be done.Eddie Martucci: The second thing is, frankly, society is demanding better medicine in many different ways. They're demanding, and mainly I'm talking about patients in many respects, they're demanding more accessible medicine. They're obviously…we all got the efficiency bug of telemedicine during COVID. And while I've seen the data that that has significantly receded, I don't think the concept of online or digital in medicine has receded from anyone's mind. I think we all know that it's far more efficient and we should expect to see more products that are digital in nature, whether that's scheduling with a doc or taking a treatment. And so I think there's this kind of wave in society that is that is pushing people to recognize that we should be open to these types of products. The other thing is, whereas docs and patients years ago when we did market research, there was a level of skepticism that was pretty healthy. I now see a level of openness where if there's good data and there's especially in our case, things like FDA approval and strong clinical data, there's a better chance than not that both patients and doctors are going to be not only acceptable or accepting, but they're going to want to at least try something like this. So all the groundwork is there. We've just got to keep keep plugging away because it's new.Harry Glorikian: I talk about the whole digital therapeutic space in my book. And I always tell people look, if a product like this works for you, you're not going to have a side effect profile the way you have with some of the small molecule drugs that I've seen. It's trial and error with those things. And sometimes things don't go as well as you want them to and you end up with a very angry child if the drug doesn't do what it's supposed to do.Eddie Martucci: It's egregious. It's egregious. I mean, medicines, pharmacological medicines for neurological conditions are critically important. Don't get me wrong, I think they're critically important. And EndeavorRx is not meant to be an alternative to medication, especially if it's working well for for a child. But the problem is, there are many components of these conditions that are just not well addressed. And so you're left as a clinician to try to use these blunt instruments, these molecules which weren't delivered for these problems or rather weren't designed for these problems. You're trying to use them, but you're fighting the side effect profile as much as you're fighting the efficacy the whole time. And so you're right. Trial and error is the right phrase. Like the fact that we're still doing trial and error in CNS conditions all these years later is crazy. And there's a better way because we now can have these more targeted products that are part of the patient's toolbox.Harry Glorikian: Yeah, and we need more of them, so. Yeah, great. But let's talk about the business model, right? I mean, this is, you know, feels like fresh territory, right? And if I think about mobile games generally don't make money unless you sell millions of copies. Right. So you have you must have a different business model in mind from the beginning. I suspect this business model revolved around, you know, selling Akili games as a prescription based therapeutic at a cost that would be more typical for a drug than a mobile game.Eddie Martucci: Right. Right. So the concept here is we want the products to get to the patients that really need them and we want to involve the doctor in the loop and we want to have products that are proven. And so all of that to me says a core medicine model, meaning prescription treatment, as you said, covered ideally by insurance largely, but with a little bit of out-of-pocket burden from the patient. You're right, the general cost is a little bit more in line with pharmacology, although the good news in mental health and behavioral health is that's that's relatively inexpensive. We're not talking about multi-thousand-dollar therapies here. We're talking about something that is in the low hundreds per month. And for the patient, really more like $30 to $50 a month. So these are the cost structures that we think are tenable and have been working well in behavioral medicine. And that's really where we're starting. But we're in the early days. I think one of the beauties of digital is we don't have to just stay there, meaning that is the core of the model, a prescription that scales and is paid for by both insurance and patient.Eddie Martucci: But I think there's a lot of potential to evolve and iterate the model that has more consumer elements to it. For instance, like your best technology products, we can adapt the product itself to grow with you. Like your best technology products. We can serve, you know, services and help on the side beyond or in between your use of the actual treatment. So there's a level of connectivity with our end user and consumer that is that actually looks a lot more like best in class consumer software where you can have a long term relationship with a patient. Now, we have not pulled any of those levers yet, but I think what we're most excited about is the bringing both of those models to bear. A medical model, but that has some aspects to it that can actually grow and extend more like software. I actually think that's where the field will go. But it is early days. We'll have to see how this we'll have to see how this shakes out.Harry Glorikian: Well, that's why I always I always tell people, like, you know, once you digitize something like you get to have a broader imagination about what is possible in that realm as opposed to, you know, sticking to exactly what we did before.Eddie Martucci: Exactly.Harry Glorikian: But taking a step back here, no one has ever marketed a prescription based video game or won marketing approval from the FDA for such a product. Right. So how did you frame yourself? You walk in there and you say, “Hey, here, play this. And you're going to like it.” What were the hurdles? What did you have to overcome to get regulatory approval for this? What was it like dealing with the FDA?Harry Glorikian: No, it's a great question. Yeah, the FDA process is fascinating. We know it is rigorous, it's long, it's mostly collaborative. Right. The FDA wants to learn and help. But I think, number one, most importantly, there's unfortunately a myth out there today that digital therapeutics are actually medical devices generally don't have to go through efficacy analysis by the FDA. So I see this myth all the time. People say, well, you know, on the medical device side, they only look at safety. And so, unfortunately, with broad brushes, people have painted digital therapeutics as part of that. They've said, well, digital therapeutics may or may not have evidence, but the FDA looks at safety. I can unequivocally tell you that could not be farther from the truth. I would say 95 percent of our interactions with the FDA, which took the better part of two years because our product was so novel, you can imagine we were not only innovating the delivery mechanism, it's a video game. We were innovating the target, which is cognitive functioning, which there are no products labeled for cognitive functioning. And we were trying to look at what are the endpoints that, you know, that read on cognitive functioning. All of this is new, but not 95 percent of the questions we had, and that's—please don't quote me on the specifics, this is not a deposition—but in that range, were about efficacy. And we went through every little bit of our efficacy data so that the FDA could understand it, so that they could audit it.Eddie Martucci: We even, midway through our regulatory process, brought on a fifth study. So we have five studies in our FDA label package. So we brought on the most recent study to show to address some questions FDA had around efficacy in the longer run or efficacy along with medication. So this was a very rigorous process. I always tell people the good news about this is you can trust it when it comes out because this is something that looks and feels a lot like the drug process, right? There's a lot of scrutiny put on the trials and the legitimacy of the trials. So so it looked a lot like that. It's highly iterative. From a business side, the one tough part with FDA is when you're when you have a new classification for a product, so a 510K de novo, so they're creating a classification, there is no hard timeline on the review. And so when you're a startup and you're building a business, you kind of just keep iterating until you get to a label or not, right? And luckily in our case, we did. But yeah, I mean, as a startup, you're going through a nearly two-year approval. It's stressful. It's stressful, but it's good for the industry, I believe, because it's really forcing a high bar of science.Harry Glorikian: Well, no. And I mean, that's what you want. You don't want a low bar and then things go wrong, like you want it to be held to a higher standard. And usually when the FDA is taking on something new, they've also got to take the time to catch up to where you are. Right. They can't just walk in the room and be ready for this. So you're sort of paving the path for everybody that's coming behind you, which is a I guess there's a good part of that and a bad part of that.Eddie Martucci: Yes. Yes.Harry Glorikian: So there's a lot of stakeholders and gatekeepers in this space that we're talking about, right. Patients, parents, physicians, payers. I mean, each one of them needs to be persuaded that digital therapy or digital therapeutics are, you know, beneficial and worth prescribing or worth paying for. So, anything special you're doing to sort of win them all over?Eddie Martucci: Well, we're doing the work to put time and attention towards it. So you're right. Just because it's digital does not mean people will use it or understand it. So you've got to sit with patients and educate. Just because docs have a new tool doesn't mean they'll trust it. So you've got to spend time to make sure they understand the data and more importantly, understand where we're trying to play in the treatment paradigm. Right. Because, again, we're not … the easy answer for a digital is, “Oh, this is supposed to be a digital equivalent of a drug.” No. It's more nuanced than that. This is supposed to help in a very specific way. And insurers are probably the biggest barrier because it's so new for them. Right. This is this is very new. They don't really, they're not really built to be able to adjudicate digital products. Right. And unfortunately, we've got some of these types of myths floating around, like the FDA medical device myth, which understandably makes insurers uncomfortable. Right. If they if that's what they've heard, they say, well, how in the world am I supposed to adjudicate efficacy if the FDA doesn't? I guess I'll look at this with all the other hundreds of wellness apps out there.Eddie Martucci: So it's education time. Honestly, it's education time to unravel these myths, to really sit and make sure these stakeholders understand the data and the utility of the product. In terms of special things, one of the one of the nice things about growing a company, especially with digital company in this day and age, is you can test and iterate really quickly on all of these fronts. And so when we test you've got to have the meetings and you've got to fit into their review cycles. But for patients and docs, you know, we, we take a very clear test and learn approach. We are releasing certain types of educational content or certain types of marketing messages in pilot phase. Right now we see what works, we see what doesn't. We adapt. We do the same thing with the distribution infrastructure, frankly. Like how in the world do you get a video game therapeutic from your doctor? We built the infrastructure. We tested, we changed, we scrapped half of it and started again. So that is the beauty of living in a digital world. We can we can do that type of testing and learning.Harry Glorikian: And good old AB testing on what works and what doesn't.Eddie Martucci: Totally.Harry Glorikian: All right, let's step out of ADHD for a minute. You've been talking about other neurophysiological sort of conditions. And I think the website, if I'm not mistaken, mentions depression, cognitive dysfunction, multiple sclerosis, autism spectrum disorder, and a few other future treatments is. Is there something about the EndeavorRx platform or the proprietary adaptive algorithm that gives you the ability to sort of generalize? And I think you mentioned that earlier, but sort of to dig into that a little bit.Eddie Martucci: Yeah. So it really starts with what technology are looking for. And so we don't source technologies that are meant for any one condition. That is more common in the behavioral therapy space where there's behavioral therapy for disease X because it's a tried and true technique specific to the disease. The way we work is looking for technologies that actually activate specific brain regions and have data that they do that well. And so the interesting thing that we found about cognitive functioning, and we knew a little bit about this, but you know, I don't like to have revisionist history and say we we knew it all, with cognitive dysfunction and disease, independent of the etiology or the cause of why the brain is having issues, the downstream manifestation actually tends to bucket into very similar issues. And so our theory was, and so far it's proven true, is if you could bring technologies that are meant for the neurological processing issues, not the disease, not specifically the disease, then any condition that results in similar issues, you should be able to have a functional impact on. Because we're not we're not targeting, you know, dopamine reuptake and a dopamine driven disorder. We're not targeting myelination in am anti-myelinating disorder. We are targeting the end result, which is how well the brain is communicating. So we've because we start there, we, we theoretically have the ability to go across disease, and we've actually shown it now. So the same technology that has a treatment label for ADHD has been able to power two studies, including a larger randomized controlled study in multiple sclerosis adults, and showed clinically meaningful, large changes in speed of processing and related cognitive functions. That's the same technology under the ADHD product. ADHD and MS could not be farther from each other in terms of cause, but because the resulting functionally in the same in the same area, that's then you get that benefit. So that's our theory and that's how we're going to continue to develop products and take a functional and a neural network approach, if you will. And, and ideally, we have a much more efficient product pipeline because of it.Harry Glorikian: So. In your mind, like what are the biggest unanswered questions, either for EndeavorRx or for the Akili business. Is it more product? Is it more market? I mean, for example, do you worry about whether it'll work, you know, in the real world, as well as it did in your initial studies, whether doctors will prescribe the game, whether payers will cover it. There's all these issues. And so I'm just wondering where you think the biggest hurdles lie?Eddie Martucci: Sure. Yeah, I think I think my number one is not about the product. It's really systemic to the to the health care system and industry, which is it's important to me that the insurance industry, the doctors write prescriptions, but more importantly, the insurance industry and broader we could call it the payer industry. Right. Anyone that should be paying for medicine pays for digital therapeutics. Right. I don't think this should be the only class of medicine where patients bear the entire cost. That makes no sense. So we are not there yet for sure. Right. We're in such the early days that I think some payers are waiting, but I think we're starting to see a turn. We're beyond skepticism, beyond intrigue, probably into early acceptance. And I think the work needs to be done. And frankly, we need we need a couple folks in this industry and by folks, I mean both people, but also organizations to step up as the early pioneers for their patients. I think that's really important. Now, again, I have empathy for why that part of the industry moves slower. They're trying to protect patients. There's obviously cost arguments as well. And there are some of these myths or misconceptions out there about the industry. But I think when education is done right and when payers really engage, we're going to start to see a broader payer ecosystem adopting this like they would any other medicine. So I think that's kind of the biggest near-term barrier. And slightly longer term, I think the business model is a question. Which no one likes to hear, no investor likes to hear. And we're a company that's going to go public. I don't mean the business model is a question in that we don't know if we can make money or build a business. I just mean, what is…so, the foundations we know are there. Doctors will prescribe, patients will pay, payers are starting to pay. It has a benefit in people's lives. So the foundations are there. The business will grow. What the eventual business model is, is TBD, frankly. What is the top end business model that's going to allow a company to thrive at scale? I think we have to invest to learn that. And I'd say the same thing about the product. In terms of the product, it's not whether it will work, it's not whether it can help patients on the market. We've shown all of that. It's at this point, how well can you develop that product on the market so that it engenders long term compliance so that engenders loyalty and use in the future? And so I think in both those scenarios, I guess the health care system's got to get there. Which is a secondary priority, more like an opportunism. We don't want to miss the opportunity to find the best business model or to iterate on the products because we have the ability to do so. I don't want to miss that opportunity to grow the best business model we possibly can.Harry Glorikian: So you mentioned going public once or twice, and so I saw that there's paperwork with the SEC to go through a public filing with a special purpose entity backed by Chamath, whose I think it was Social Capital, through his venture fund. What's the thinking behind becoming public? Why now?Eddie Martucci: Yeah. I think I always had a mantra and I didn't come up with it. This is from advisors to me and mentors: Stay private as long as you possibly can for the business to be able to adapt and iterate and a little bit more of a clean way. But I think that time has come, and the reason I say that is we have a product that is being prescribed by doctors now and we have a pipeline where I've already talked about it. We could help potentially up to dozens of different populations who are struggling today. On top of that, the need and urgency around mental health and behavioral health has had a step function change in the last year. Right. We know that President Biden talked about it at the State of the Union. The surgeon general has put out a national state of emergency on youth mental health. So the time is right for a real investment here and the time is right for the company to fill that need. We know all the all the foundations are right. So I've always wanted to wait till that moment why we chose this specific entry point and vehicle, which we hope is kind of middle of this year, that Akili becomes a publicly listed company is, I think, the opportunity to not only have capital and the type of flexible capital that the public markets gives you, but in the case of a special purpose acquisition company, the expertise of that acquiring entity, in this case, Chamath Palihapitiya, who's extremely well known and amazing at building disruptive technologies for different industries that scale to ubiquity using technology and data.Eddie Martucci: But actually that the SPAC vehicle here is Social Capital Suvreta. Suvreta being a well known biotech hedge fund who specializes in early commercial biotech companies. So rarely do you get to become public with the right amount of capital, but also some new expertise around the table, strategic expertise in a disruptive business. And I think we get both of those with this deal. So we're still, it's too early to tell if the whole thing will go through. We're certainly crossing our fingers and hopefully if people listen to this in the longer future, Akili is already a public company and thriving.Harry Glorikian: Well, I mean, it's a good thing I spoke to you now so that we could speak a little bit more freely than when you're under that public rubric.Eddie Martucci: But oh, no, I'm already I'm already watching my words. It is important. It's a level of maturity as a business. Now, we have we've grown for about a decade. We grew methodically and slowly. We have over 100 employees now. And, you know, businesses change and mature. And I think it's the right time for us to do it.Harry Glorikian: Oh, yeah. I mean, a lot of the companies that I interact with as an investor, I mean, when we're going to go public, it's like, “Oh, we got to do this, we've got to get that ready. We got to get accounting ready. We got it.” I mean, you've got to go through it methodically because being public is is not for the faint of heart for sure. So, well, I wish you the greatest success. I look forward to staying in touch and, you know, keeping up to date on how things are going with the company. And, you know, I hope a ton of people listen to this because it's easier for them to hear it from you than hear it from me.Eddie Martucci: Thanks, Harry. This is a lot of fun. And thanks for your focus in innovation and these new areas that are really going to transform patients' lives. So I'm hoping we're doing our part there.Harry Glorikian: Thanks.Harry Glorikian: That's it for this week's episode. You can find a full transcript of this episode as well as the full archive of episodes of The Harry Glorikian Show and MoneyBall Medicine at our website. Just go to glorikian.com and click on the tab Podcasts.I'd like to thank our listeners for boosting The Harry Glorikian Show into the top three percent of global podcasts.If you want to be sure to get every new episode of the show automatically, be sure to open Apple Podcasts or your favorite podcast player and hit follow or subscribe. Don't forget to leave us a rating and review on Apple Podcasts. And we always love to hear from listeners on Twitter, where you can find me at hglorikian.Thanks for listening, stay healthy, and be sure to tune in two weeks from now for our next interview.

Dr. Stephen Cabral is back on the podcast today and I always enjoy speaking with him. He is such a wealth of knowledge and information. We spend our time today talking about how to lower your biological age, live longer, and look younger. And he gives a lot of evidence-based ways to do this. In …

We've all had days where your energy seems to be missing. Often we look at the hours of missed sleep or sit in confusion with how it feels like we've slept enough hours. Dr. Steven Gundry is a cardiac surgeon that has been educating himself, his patients, and many others about why diet is key to restoring and improving energy levels. Everything you consume comes in contact with your microbiome and Dr. Gundry is simplifying why your gut health is critical to how your body is able to absorb what it needs and provide you with the energy you need to take on much bigger goals in life. The connection between gut health, energy, lifestyle, and how we age is one of the most important things you can dedicate time to understanding for your future self.SHOW NOTES:0:00 | Introduction to Dr Steven Gundry0:08 | Diet Tip to Improve Your Skin8:30 | Lectins Found in Animal Meat13:43 | Why Limit Animal Proteins18:55 | Intermittent Fasting & Burning Fat21:51 | What to Include in a Healthy Diet24:17 | Fat Impact on Your Microbiome31:33 | When Carnivore Diets Are Best35:08 | What Passing Gas Signals to the Body43:29 | Mitochondria Energy Process46:48 | Leaky Brain, Alzheimers, and Cholesterol52:00 | Fecal Microbial Transplant57:59 | Microbiome, Gut Feelings and Autism1:03:16 | Lifestyle & Diet For Aging WellQUOTES:“We have to realize that our chickens are no longer chickens, they're an ear of corn with feathers.” [12:58]“Believe it or not, in the American diet 24 hours a day, we're causing leaky gut, we're assaulting our immune system…” [26:37]“If we look at energy production, as literally cars moving down through a freeway, it's no wonder that even though we're eating huge amounts of calories, we have no energy…” [46:03]“Compared to women who don't exercise routinely, and in the women who are going to get Alzheimer's, it's 11 years later than if they didn't exercise.” [1:05:48]Follow Dr. Steven GundryWebsite: https://gundrymd.com/Instagram: https://www.instagram.com/gundrymd/Facebook: https://www.facebook.com/GundryMD/YouTube: https://www.youtube.com/channel/UCtxo0nTZjzlKJq5-vJq6s6g

The main reason to own a parrot, hollow earth, Savage Crucible, eating lion's @$$, the best way to get out of jury duty, and more! I may not even understand all this

The main reason to own a parrot, hollow earth, Savage Crucible, eating lion's @$$, the best way to get out of jury duty, and more! I may not even understand all this

DR BECCA LEVY is the Professor of Epidemiology and the Chair of the Yale School of Public Health, Social & Behavioral Sciences Department. She is also a Professor of Psychology in the Yale University Department of Psychology. She is the leader and pioneer of a field of study that focuses on how both positive and negative age stereotypes affect the health of older individuals and has led WHO efforts to investigate the impact of ageism on the health of older people. She has published many articles, won numerous awards for her work and been cited widely across the media. She speaks extensively about her work around the world, including in the UK, Singapore, Korea, Germany, Switzerland and of course the US.Her new book is called, 'Breaking the Age Code: How Your Beliefs About Ageing Determine How Long and Well You Live'Amazon US Amazon AUSPre-order my new book 'The Path of an Eagle: How To Overcome & Lead After Being Knocked Down'. https://www.amazon.com/dp/163758492XFollow The Story Box on Social Media► INSTAGRAM ► TWITTER ► FACEBOOK ► WEBSITE Support this show http://supporter.acast.com/thestorybox. See acast.com/privacy for privacy and opt-out information.

While you can't control your age, the good news is, you can slow the aging process and decrease belly fat with smart lifestyle choices. Belly fat is linked to an increased risk of many diseases. “How do I lose the belly fat?” is one of the most common post pandemic questions I hear. Let's talk about some of the common mistakes I see in lifestyle choices & how to fix it so that you can increase performance, lose weight & live longer. Tune in today!  

“Stress can drive aging forward like gasoline on a fire.” – Dr. Fitzgerald Can we reverse our biological age and create a healthier life? That is what we explore with the cutting edge research of Dr. Kara Fitzgerald, the author of “Younger You: Reduce Your Bio Age and Live Longer, Better“. “By eating delicious foods and establishing common-sense lifestyle, study participants reduced their bio age by just over 3 years in only eight weeks!” Dr. Fitzgerald helps us understand epigenetics, the role of DNA methylation in aging, the future of nutritional epigenetics, and more! This is a fascinating conversation and you can tune in now and access the show note at https://thegoodlifecoach.com/178 Join my newsletter and get a free copy of my book, “Design a Life You Love”. WE DISCUSS: 1️⃣ Epigenetics – the science of studying what turns on gene expression. 2️⃣ The way we turn gene expression on and off is through DNA methylation. 3️⃣ How as we age our DNA methylation starts getting “wonky” and how lifestyle management can help. 4️⃣ How bio age is the biggest risk factor for chronic disease. 5️⃣ Her study and how it showed that they could turn back aging by just over 3 years in 8 weeks. 6️⃣ How reversing biological age by just one year would save trillions on healthcare in the US 7️⃣ The studies that show how our ancestors trauma impacts our gene expression. 8️⃣ “Meditation can change our epigenetics towards longevity.” – Dr. Fitzgerald ABOUT OUR GUEST Dr. Kara Fitzgerald is the first-ever recipient of the 2018 Emerging Leadership Award from the Personalized Lifestyle Medicine Institute in recognition of her work on DNA methylation. As a leading voice in the intersection of nutrition, epigenetics, and aging, Dr. Fitzgerald's work has been featured in media outlets such as Prevention, Fast Company, MSN, Everyday Health, and many more. Receiving her doctorate from National University of Natural Medicine, she is on the faculty at the Institute for Functional Medicine (IFM) and is an IFM Certified Practitioner with a clinical practice in Newtown, Connecticut.  She's also the author of “Younger You: Reduce your Bio age and Live Longer, Better”. RESOURCES MENTIONED Book: Younger You Website for Program: Youngeryouprogram.com Practice/Podcast Website: Drkarafitzgerald.com App: 3YY – find it on apple store IG: https://www.instagram.com/drkarafitzgerald/?hl=en Michele's Book: Design a Life You Love Michele on Instagram Thank you for listening to the show!

Why is hibernation something that bears and squirrels do, but humans don't? Even more interesting, what's going on inside a hibernating animal, on a physiological and genetic level, that allows them to survive the winter in a near-comatose state without freezing to death and without ingesting any food or water? And what can we learn about that process that might inform human medicine?Those are the big questions being investigated right now by a four-year-old startup in California called Fauna Bio. And Harry's guests today are two of Fauna Bio's three founding scientists: Ashley Zehnder and Linda Goodman. They explain how they got interested in hibernation as a possible model for how humans could protect themselves from disease, and how progress in comparative genomics over the last few years has made it possible to start to answer that question at the level of gene and protein interactions. The work is shedding light on a previously neglected area of animal behavior that could yield new insights for treating everything from neurodegenerative diseases to cancer.Please rate and review The Harry Glorikian Show on Apple Podcasts! Here's how to do that from an iPhone, iPad, or iPod touch:1. Open the Podcasts app on your iPhone, iPad, or Mac. 2. Navigate to The Harry Glorikian Show podcast. You can find it by searching for it or selecting it from your library. Just note that you'll have to go to the series page which shows all the episodes, not just the page for a single episode.3. Scroll down to find the subhead titled "Ratings & Reviews."4. Under one of the highlighted reviews, select "Write a Review."5. Next, select a star rating at the top — you have the option of choosing between one and five stars. 6. Using the text box at the top, write a title for your review. Then, in the lower text box, write your review. Your review can be up to 300 words long.7. Once you've finished, select "Send" or "Save" in the top-right corner. 8. If you've never left a podcast review before, enter a nickname. Your nickname will be displayed next to any reviews you leave from here on out. 9. After selecting a nickname, tap OK. Your review may not be immediately visible.That's it! Thanks so much.TranscriptHarry Glorikian: Hello. I'm Harry Glorikian, and this is The Harry Glorikian Show, where we explore how technology is changing everything we know about healthcare.It's April and spring is well underway, even though it's been a pretty cold one so far here in New England.It's the kind of weather that makes you want to pull the covers over your head in the morning and just sleep in. Or maybe just hibernate like a bear until summer is really here.But when you think about it, what is hibernation? Why is it something that bears and squirrels do, but humans don't?Even more interesting, what's going on inside a hibernating animal, physiologically, that allows them to survive all winter without freezing to death and without ingesting any food or water?And what can we learn about that process that might inform human medicine?Those are the big questions being investigated right now by a four-year-old startup in California called Fauna BioAnd my guests today are two of Fauna Bio's three founding scientists: Ashley Zehnder and Linda Goodman. I asked them to explain how they got interested in hibernation as a possible model for how humans could protect themselves from disease.…And how progress in comparative genomics over the last few years has made it possible to start to answer that question at the level of gene and protein interactions.We've always looked to the natural world, especially the world of plants, for insights into biochemistry that could inspire new drugs. But what's exciting to me about Fauna Bio is that they're shining a light on a previously neglected area of animal behavior that could yield new insights for treating everything from neurodegenerative diseases to cancer.So, here's my conversation with Ashley Zehnder and Linda Goodman.Harry Glorikian: Ashley. Linda, welcome to the show.Ashley Zehnder: Thanks, Harry, we're excited to be here today. It's going to be fun.Linda Goodman: Yeah, thanks for having us.Harry Glorikian: Yeah, I mean, well, you guys are someplace sunny and warm, and I'm actually I shouldn't say that it's actually sunny right now on the East Coast. So I'm not I'm not.Linda Goodman: Don't jinx yourself.Harry Glorikian: But the temperature is going to drop. Like to I think they said 18. So everything will freeze tonight for sure. So it'll, you know, it's one of those days, but. I want to jump right into this because we've got a lot of ground to cover. Like there's so many questions that I have after sort of looking into the company and sort of digging in and, you know, but even before we jump into what you're working on. Right, I really want to talk about hibernation. Maybe because I'm jealous and I'd like to be able to hibernate. I have sleep apnea. So sleep is a problem. But humans don't hibernate. But there's a ton of other mammalian species that that do. And sometimes I do feel, though, that my teenager hibernates, but that's a different issue. So, but, what what is interesting to you about hibernation from a physiological point of view. What what goes on with metabolism or gene expression during hibernation, that's that's not found in humans, but that could be relevant to human health?Ashley Zehnder: Yeah, I think this is a great question, Harry, because I think both Linda and I came to fauna from different backgrounds. I came from veterinary science, Linda from comparative genomics. We can go into our details later, but neither of us really appreciated the amazing physiology of these species. There are some of the most extreme mammals on the planet, and there are hibernating bears and literally every group of mammals. Right. This is something Linda specializes in. But there are primates in Madagascar that hibernate very similar to the 39 ground squirrels that we tend to work with. So it's this really deeply conserved trait in mammals, including primates. And, you know, it kind of highlights for us what our genes can do when they're adapted for extreme environments. And so that's kind of the lens that we take when we look at hibernation. It's how do these species protect their own tissues from being nearly frozen for six, seven months out of the year, having to protect their brains, their hearts, all their vital organs? They're not eating, they're not drinking. They're not moving for these really deep bodied hibernaters. When you think of 100 kilogram animal that's not eating for seven months, how do they survive that? Right. And it has to do with metabolic rates that change 200- to 300-fold over the course of a couple of hours. It has to do with oxygenation changes and protection from oxidative stress and ischemia reperfusion. And so if you look at a tissue by tissue level, you can start to see how these animals are finally adapted to protecting themselves from from damage. And then we can start to say, well, this is similar damage to what we see in human diseases. And that's why this is such an interesting system, because it's so dynamic and because it happens across so many groups of mammals, it really lends itself to this comparative genomics approach that we take to drug discovery.Harry Glorikian: Yeah. Because I was wondering sort of like what ways of healing from different sort of traumas and conditions do hibernating animals have that that humans don't, that we sort of maybe wish we did? It's sort of like, you know, almost Marvel or one of those things where you like go to sleep, you wake up, you've totally healed again, which kind of be kind of be cool. Yeah. So, you know. But when did scientists first begin to think about whether having a better understanding of hibernation might help us solve? Some of these riddles that we have in human health. I mean, it surely it can't be like a new concept. It has to go further back. I mean, what has changed recently to make it more actionable? I mean, is it, you know, omics, costs coming down that are making it easier, computational capabilities that are, you know, making all these come together? I mean, those. What do you guys. What's. What's the answer? You guys know the answer better than I do.Ashley Zehnder: I'll comment on a little bit on the physiology, and I will let Linda talk about the data revolution, because that's that's really what she knows very intimately. So from a physiology standpoint, these are species and not just hibernaters, but a lot of other species that we've been studying since the early 1900s, 1950s. I mean, these are some of our earliest biological experiments and our earliest understandings of biology. We're not necessarily done by studying humans. A lot of that was done by studying natural disease models, right? How did we figure out that genes cause cancer? So it's a little bit of a tangent, but bear with me, it was not by studying human cancer, it was by studying Rous Sarcoma Virus and how that virus picked up bird genes and then turn them on. Right and other in other individuals. So but then kind of this almost the same year in 1976 that we figured out that genes cause cancer by studying chickens. 1974 we figured out how to genetically modified mice. And we sort of figured out that like, okay, maybe we don't need to study natural biology anymore. And so I feel like we sort of lost a lot of those skills and figured out we had humans and we had model organisms and we were done. And I think now we're kind of in this renaissance where people are realizing that actually there's still a lot of natural biology that we can learn from. But it's being powered now by this data revolution and the decrease in cost and sequencing and availability of omics data like RNA. Seq and then I will pitch that over to Linda because that's really what she knows best.Linda Goodman: Yeah, yes, absolutely. You know, Ashley's right. And I think just to add on to that, that there was this issue in which there were a lot of field biologists out there working with these really fascinating hibernating animals. They knew a lot about what these animals could do, the extreme environments they were exposed to, that they could overcome, they could protect all of their tissues. And there was so there was a group of field biologists who knew all that information. And then on the other side, you have all of these geneticists who are studying the genomes of probably humans and mouse and rat. And they weren't really talking to each other for a long time. And I've been in the genomics field for at least a decade, and not until very recently did I even hear about all these amazing adaptations that these hibernating mammals have. So I think some of it was just a big communication gap. And now that the genomics field is starting to become a little more aware that all these exciting adaptations are out there that we can learn from, I think that's going to be huge. And yes, of course, it certainly does not hurt that there's been a dramatic drop in sequencing costs. We can now sequence a reference genome for around $10,000. That was unheard of years ago. And so a lot of these species that people would previously consider untouchables because they were not model organisms with a pristine reference genome, we can now start to approach these and thoroughly study their biology and genomics in a way that was not possible several years ago.Harry Glorikian: Yeah. I was thinking I was, you know, I was laughing when you said $10,000, because I remember when we did the genome at Applied Biosystems and it was not $10,000.Ashley Zehnder: Yeah.Harry Glorikian: Yeah. And it took I remember Celera, we had an entire floor of sequencers working 24/7 I mean, it was an amazing sight. And now we can do all that, you know, on a.Ashley Zehnder: Benchtop. Benchtop. Exactly. On a benchtop.Harry Glorikian: So. But, you know, it's interesting, like in a way, studying animals to learn more about disease mechanisms seems like a no brainer. I mean, we share a, what, about 99% of our DNA with chimpanzees. And for those listening. Yes, we do. You know, I'm sure there's people out there that, like, bristle when I say that. But what is it, 97.5% of our DNA with rats and mice. That's why we use all these things for sort of safety and effectiveness of drugs meant for humans. But. Still, I'm not used to drug hunters starting out by looking at animals, you know? Why do you think it's taken the drug industry, although I'm I say that very loosely, [so long] to wake up to that idea?Ashley Zehnder: Yeah. I think it's I think it's again, this almost reversal of the paradigm that exists today, which is let's take a human disease that we want to make a new drug for. Let's take a mouse and let's try to genetically manipulate that mouse to mimic as closely as possible what we see in the human disease. And those are always imperfect. I mean, I did a cancer biology PhD at Stanford, and there's that trope of like, Oh, if I had a dollar for every time you occurred mouse in a human right, it would need to work anymore. That's replicated across many fields, right? They're not good models. And so we're saying like obviously that doesn't really work for discovery. It's fine for preclinical and safety and you have to use those models. But for pure discovery, that's not where you want to be, right? Instead, you want to take the approach of saying, where has nature created a path for you? Where is it already solved this problem? And I think there are companies like Varian Bio who are doing this in human populations. We're saying, let's look at humans that have unique physiologies and a unique disease adaptations. And of course then you have to find those niche pockets of human populations.Ashley Zehnder: So that's not a not a simple problem either. But the approach is very analogous. What we're saying is we can use that rare disease discovery approach and just expand that scope of discovery. Look at highly conserved genes, look at how other species are using them to reverse how phosphorylation in the brain to repair their hearts after damage, to reverse insulin dependence. To heal, we'll heal their tissues or regenerate stem cells. Let's just see how nature did it right and just mimic that instead of trying to fix something that we artificially created. So it's literally reversing that paradigm of how we think about animals and drug discovery. But you have to know how to do that. You have to know which models are correct. You have to know how to analyze 415 genomes together in an alignment which is really complicated. Linda knows how to do that, so you have to know how to do it correctly, although you could screw it up very badly. So there's a lot of expertise that goes into these analyses and also again, the data availability, which wasn't there nearly a decade ago. So.Harry Glorikian: So I asked this question out of pure naivete, because I'm not sure that I could sort of draw a straight line. But, you know, which drugs were have been discovered through research on genetic mechanisms of disease in animals. Is there, are there?Ashley Zehnder: You know, I think directly it's a new field. Right. So I think, Linda, you and I have looked at some examples of looking at drugs for narcolepsy, looking at dog genetics and studies, looking at muscle disorders in certain species of cattle that have naturally beefed up muscles and translating those into therapies. I mean, there are examples of looking at animals for things like genotype, right, came from Gila monster venom, although that's not strictly a genetic program. Right? So I think this idea of looking at natural animal models is a source of innovation. It's just that, again, the data wasn't really available until fairly recently, but we know the strategy works by what's been done on things like PCSK9 inhibitors in humans, right? It's a very similar approach to that. It's just expanding that scope of discovery.Harry Glorikian: So because you guys raised money and you guys are moving this forward, sort of and I don't want you to tell me anything that's confidential, but. So what was the pitch when you when you put that in front of everybody?Ashley Zehnder: It was really that, look, drug discovery right now is really been hampered by a lack of innovation. And we're really stuck in looking at these very kind of currently limited data sources, which is humans and again, these handful of really imperfect animal models. But we can take what we've learned from working with human genomics and really greatly expand the opportunities for a number of diseases that still don't have good therapies. Right. We've had the human genome for really close to 20 years now. We spent a lot of money sequencing it. And still, if you go back and look at the FDA approvals in the last two years, which I did by hand a while ago, or more than three quarters of those are not new targets. They're new drugs for a new indication or new drugs, same drugs before a new indication or they're kind of meta pathway drugs or they're drugs for which we still don't know the mechanism. It's some small molecule. It's been around since fifties. And so like where is the innovation in the top ten diseases of people still have it changed? So like where I pulled these two headlines right not too long ago, one from 2003, which is like the era of the genomics revolution. Right? And then one from 2019, which was the genomics revolution question mark. Right. Like we're still sort of waiting for it. And so what is that missing piece of data that's really going to allow us to really leverage the power that's in the human genome? And to do that, we have to put our own genes in an evolutionary context to understand what's important. That's been that third dimension of genomics that's been missing. So it's really not necessarily about any particular species that we work on, all of which are amazing. It's really about using that data to shine a better light on what's important in our own genome. And so that's a lot of the pitches, like how are we going to use our own genome better and find better treatments?Harry Glorikian: Yep. Understood. So. You have a third founder, Katie Grabek. Right. So. Tell me about yourselves. I mean, did the three of you get interested in comparative genomics and hibernation? How did you come together? How did you decide like, oh, hey, let's do a startup and get this thing going in this area? So tell tell me the origin story.Ashley Zehnder: Linda, do you want to kick off?Linda Goodman: Sure. I think it all really started, Ashley and I initially started batting a few ideas around. We both had this understanding that that drug discovery today did not look outside of human mouse rat very much. And we both understood there was this wealth of animal data that's just waiting to be used and no one was doing it and we couldn't really figure out why. And we were having trouble figuring out exactly which animal we wanted to study and which diseases we wanted to study. And it just so happened that we lucked out. There was another woman in our lab at Stanford, Grabek, who had the perfect study system for what we were thinking about. She had these amazing hibernates our animals that have exquisite abilities in terms of disease, resistance and repair. And once she started talking about all the amazing phenotypes these animals have, we thought, wow, that would make a great study system to make the next human therapeutic. Yeah. And I think it's interesting that both Katie and Linda have human genetics PhDs. Right. So I think both of them and Linda can expound on this. But from Katie perspective. Right, she she went in to do a human genetics Ph.D. trying to understand how genes can be used to improve human health and shouldn't be rotating the lab of somebody who studied the 39 ground squirrel and said this physiology is way more extreme than anything we see in humans, but they're doing it using the same genes.Linda Goodman: What are those genes doing in these animals that we can adapt for human therapeutics? And so she brought that work with her to Stanford and was really one of the preeminent researchers studying the genetics and genomics of these species. My background is I'm of Marion, so my clinical training is in exotic species. So as a clinician, I treated birds, mammals, reptiles and saw that they all presented with different kinds of diseases or in some cases didn't present with diseases like cancer that were super interesting. And then coming to a place like Stanford to do a PhD, it was working with a bunch of human researchers, human focused researchers. They're all generally human researchers, but you know what I mean? It's a little bit tricky with the nomenclature. Generally, I have my doubts about, you know, maybe there's some chimpanzees doing research somewhere, people studying human diseases, right from a human lens who are completely ignorant of the fact that animals often also had these disease traits or in some cases were resistant to them. So there was this huge disconnect there of of biologists and veterinarians and physiologists who understood all these traits across different species and the people who knew the molecular mechanisms, even though a lot of those are shared.Linda Goodman: And so one of the things that I found really interesting just from a cancer perspective was that a lot of our major oncogenes are highly conserved because these are core biological genes that if you screw them up, will give you cancer. But there's an evolutionary pressure to maintain these genes. And so there's a reason why they're conservative, because they're really important biologically, and that's true across many other diseases as well. So from that perspective, I was really interested in this intersection of human and animal health. I always wanted to do more genomics myself and just never had had the training. Linda had always been interested in veterinary science, and so we kind of immediately started collaborating and saying, Look, look, there's a huge opportunity in this, again, third space, third dimension of genomics that people are not looking at. What do we do trying to start a comparative genomics company? I'm using air quotes here for the podcast listeners is a little bit broad. Where do you start? And I think Katie really gave us that start in saying, here's a model. We have a biobank of samples that are proprietary to fauna. We have an expert in this field. We have a model that's good for so many different diseases. Let's prove that the process works here and then we can expand into multiple disease areas.Harry Glorikian: You know, you got to love, people I think, underestimate that magic that happens when the right people get together and the spark happens, right? I mean, I'll take that. Any day. I mean, I love coming up with a plan and then, you know, working to the plan. But when it happens, when the right people in the room and they're all get excited, those are those are the most incredible start ups, in my opinion. Yeah. So you're starting off with targets in heart disease, stroke, Alzheimer's, diabetes, very different areas, right? Cardiovascular, neurodegenerative and metabolic. So. Why start with those areas in particular?Linda Goodman: So I think for us it was really again showing showing what we can translate from this model. So some of the phenotypes that we see, the traits that we see in the ground squirrel, which is predominantly one of the species we use for our work, is that they're exquisitely resistant to ischemia, reperfusion injury. So the kind of injury that gets, if you have a heart attack and you go and get the heart attack on block, you get this rush of warm, oxygenated blood back into your heart that can actually be damaging. And that's a lot of what causes damage after a heart attack, what these animals happen, they do this 25 times over the course of a 6 to 7 month hibernation cycle. And if you look at their hearts in the peak of one of these periods, there is an upregulation of collagen, which is cause of fibrosis. There's an upregulation, there's histologically, there's a little bit of damage. It's less than you would I would have, but there's a little bit there. But if you get to the end of that whole cycle and look at their hearts, they look normal and they do it again next year. Right. So you and I could not survive 25 of these attacks over six or seven month period, right? Obviously not. So let's pick the strongest phenotypes we have in these animals and let's show that we can use information from that and come up with genes and compounds that are protective in our more standard models of these diseases.Linda Goodman: And that's what we did really with the first round of data that we had is we generated four genetic targets and two compounds that came out of the heart data that we had from hibernating and that we tested them in human cardiomyocytes in a dish and said if we take oxygen and glucose away from these cells, they get really unhappy and die and we could double survival of human heart cells in a dish. And then we said, okay, great, let's actually move this into animals. And so we used AAV or some of these viral vectors to then knock down genes in vivo in hearts of rats. So we literally tied off a coronary artery and then let the blood come back in and saw that we could almost fully protect these hearts from damage by knocking down genes that we found in the hibernating data. So it was really closing that loop and saying, where are the strongest traits? Can we show that this works? And then it was really figuring out where are the really large areas of unmet need. And so in terms of metabolism, we end up connecting with Novo Nordisk, which is a publicly disclosed partnership. They are very focused on obesity. We have a model that increases this metabolism, 235 fold over an hour. Name another model that can do that, right?Harry Glorikian: I need that. I need that. I need like, because...Ashley Zehnder: We all need that!Harry Glorikian: I could get rid of a few pounds right around here.Linda Goodman: Exactly. So then it's really just figuring out where are the unmet needs, who is really interested in these areas we're looking at and do we have unique data that speaks to those models? And that's really we just try to be guided by the biology and saying, where do we have unique data sets that can answer high unmet needs?Harry Glorikian: Okay. Well, all I mean, all sounds super exciting if we can make the translation, you know, in the right way and find those targets. But. You guys have built up a significant biobank, right? I understand you have a huge database of genomic readout from various hibernating animals. Can you tell us a little more about the extent of that biobank? How did you collect the data and how unique is that database in the industry?Ashley Zehnder: Yeah. Linda, do you want to talk a little bit about the data sources that we're currently using at Fauna?Linda Goodman: Yeah. So maybe, you might be the best person to talk about the Biobank and then I can talk about all the other data sources layering on top of that.Ashley Zehnder: Yeah, I'll talk a little about the BiobanK. So we have yeah, we have a number of different data sources. The Biobank is one of them and probably one of the main ones that we use. So Katie, during her PhD, built a really unique biobank of very precisely time tissue samples from 39 ground squirrels across the whole hibernation cycle. And the reason why that timing is so important is because the cycle is so dynamic. If you don't have really precise sample timing, you end up with a big kind of smush of data that you can't tease apart by having really precisely timed data points, you can separate these genes into clusters and know exactly kind of where you are in time. And that timing relates to the physiological injuries that we study. So we know what time points their hearts are protected because those physiological studies have been done. We've looked at those time points very specifically. So we have that biobank of samples that we in licensed as founding IP at Fauna CANI literally drove it across the country in a U-Haul because we didn't trust anybody to move it. So that's that's now in our freezers and Emeryville with a cadre of backup batteries to protect it.Ashley Zehnder: So that's the founding data that we have. And that's been really crucial because I look at other companies trying to use data for drug discovery, particularly in the early stage. A lot of it is kind of publicly available data or cell lines or kind of shared data sources. And part of what is unique about font, as we literally have truly novel data sources that we're starting with that are wholly owned that we control and we know the quality of those. So that's really the Biobank that we have is and it's 22 different tissues. I mean, it's brain, it's kidney, it's lung, it's hard. It's liver or skeletal muscle. Right? Pretty much every kind of tissue you would want in that founding biobank. But then on top of that, I think what we've done with the other data is super important. Yeah. And so we layer on top of that all sorts of publicly available data and also data we've been able to source, such as human data from the UK Biobank. But I really want to hit on the point of, of why the model species hibernate or data is so different. All of the other data that most people work with is trying to compare animals that are healthy to animals that are diseased, or people that are healthy to people who are have disease. What's really unique about the model species that we're working with is we're trying to figure out why they have these superpowers in terms of disease, resistance and repair.Ashley Zehnder: So it's kind of the other end of the spectrum that we're making this comparison between a normal, normal hibernate or during, say, the summer months and then a hibernate or that has gene expression patterns that mean that it's resistant to many diseases and it can repair tissues when it gets damaged. So it's actually quite different from the normal types of comparisons that others would make. But yes, and then we integrate publicly available data from sources like Open Targets Reactance. And one of the other data sets that we work with that's that's valuable is that we go back through literature that is relevant to the disease, indications that we're going after. And we have a team of curators that mines these papers that where the biology is relevant and we integrate those transcriptomic studies generally into our database. And that that really helps with our comparisons. And I can kind of give you an example of the way that we would do this type of cross-species analysis compared to what other what others in the industry might do if they were just looking at humans or say, just looking at mouse and rat is that, you know, if you're if you're just looking at at a human study and you're trying to say, look, for what genes do we think are involved in heart failure? You would look at, say, transcriptomic, differences between healthy human hearts and failing human hearts.Ashley Zehnder: And then you would have some type of gene list where you'd see the genes that have differential regulation between those two groups. And it fa not we we look at that type of data and then we also look at hibernate or data and then we can compare that. And that's really where the magic happens because we can look at hibernate hours when their hearts are protected during the winter months. So we have an example of these are genes that are involved in protection and then compare that to the summer months where they're not protected. And then we can integrate both of those to analyses so we can say what's really different about a human heart when it is failing to a hibernating heart when it is protected. And we do very fancy types of network analyses and then we layer on all of these data from external sources and the really exciting moments where we see these networks light up with the exact regulation patterns we are expecting that is relevant to our biology. Those are really fun. And I would say the other data source, Linda, that would be good to touch on is the genomic data, right? I think the comparative genomics data. So maybe give a little context on that. I think that really broadens the the views point of what we work with.Linda Goodman: Yeah, absolutely. So that's another data source that we work with. We have a collaboration with the Broad Institute that is one of the leaders of the Zoonomia Project that has in the neighborhood of 250 mammals in a in a big alignment. So we can do comparative genomics across all of these animals. And what we like to look for are comparing the genomes of animals that have a specific phenotype to others that don't. So for example, what is different in the genomes of hibernaters compared to the mammals that cannot hibernate? And we typically do this with how fast or slow evolving genes are, right? So if a gene doesn't accumulate very many mutations in hibernate hours, then it's probably pretty important for hibernation because there's a lot of purifying selection on that versus say, in other mammals that are not hibernaters, like like a human or a rat. It got a lot of mutations in it because it didn't matter as much for those animals. So that's another way of pinpointing the genes that are really important to hibernation. And we know, of course, that some of those might relate to the overall hibernation trait, but many of them are going to be disease relevant because they've had to evolve these genes in a way to protect their hearts and their other organs from these extreme environments they're in during hibernation.Harry Glorikian: So that, if I'm not mistaken, so did the Zoonomia Consortium, there was a big white paper about comparative genomics published in Nature.Ashley Zehnder: Nature last year? Yep. Two years ago. Yeah. A little bit.Harry Glorikian: Yes. Time seems to blur under COVID.Ashley Zehnder: Yeah.Harry Glorikian: How long have I been in this room? Wait. No.Harry Glorikian: But. Can you guys I mean, because doing comparative genomics is not, you know. It's not new necessarily, but can you guys summarize sort of the. Arguments or the principles of that paper, you know, quickly. And then, you know, my next question is going to be like, do you feel that Fauna Bio is part of a larger movement in science and drug discovery that sort of gaining momentum? So I'll, I'll I'll let you guys riff on that launch.Ashley Zehnder: Linda, you're you're the best one to do a perspective on that paper for sure.Linda Goodman: Sure. Yeah. You know, I think this is really born out of the concept that in order to identify the most important genes in the human genome, we need to be looking at other animals and more precisely, other mammals to see their pattern of evolution. Because if you see a gene that looks nearly identical across all other mammals, that means that it's really important. It means that it has been evolving for somewhere in the neighborhood of 100 million years, not accumulating mutations, which really translates to if you got damaging mutations in that gene, you were a dead mammal. Those have been selected out. And that's really how you can tell these are the key genes that are important to to your physiology, the difference between life and death. And you can't understand those things as well by just looking within humans and human populations. We're all too similar to each other. But it's really when you get to these long time scales that the statistics work out where you can see, okay, this has been this mutation has not happened in 100 million years. We don't see it in anybody's genome. So that is obviously very important. And that's just this other way of looking at our own human genome that helps highlight the genes that are going to be important to diseases. And I think, you know, another side to this paper related to conservation and the fact that a lot of these animals with really exciting genomes, the ones that are exciting to people like us, are those that have these really long branch lengths where they're they're kind of an ancient lineage. And that's really where the gold is, because that helps us even more understand how quickly or slowly some of these genes are evolving, and it related to trying to conserve some of these species as well.[musical interlude]Harry Glorikian: Let's pause the conversation for a minute to talk about one small but important thing you can do, to help keep the podcast going. And that's leave a rating and a review for the show on Apple Podcasts.All you have to do is open the Apple Podcasts app on your smartphone, search for The Harry Glorikian Show, and scroll down to the Ratings & Reviews section. Tap the stars to rate the show, and then tap the link that says Write a Review to leave your comments. It'll only take a minute, but you'll be doing a lot to help other listeners discover the show.And one more thing. If you like the interviews we do here on the show I know you'll like my new book, The Future You: How Artificial Intelligence Can Help You Get Healthier, Stress Less, and Live Longer.It's a friendly and accessible tour of all the ways today's information technologies are helping us diagnose diseases faster, treat them more precisely, and create personalized diet and exercise programs to prevent them in the first place.The book is now available in print and ebook formats. Just go to Amazon or Barnes & Noble and search for The Future You by Harry Glorikian.And now, back to the show.[musical interlude]Harry Glorikian: I should say congratulations because you guys did raise a $9 million seed round last fall from a group of venture funds, some in life sciences, some more general. Right. What does that funding do? What is it? What does that unlock next?Ashley Zehnder: You. I will answer that question. I do want to jump back to your other question that was kind of is this part of a larger movement and comparative genomics? Right. I think that's an important question. I think you sort of hit the nail on the head there. We were invited to a symposium in August of 2019 called Perspective and Comparative Genomics that was held at NHGRI in Bethesda. And I think there's a recognition and actually some of our grant funding is also through NHGRI. And I think there's a recognition from the folks who sequenced the human genome, that they don't have all those answers. And so it's an interesting time where we realize that there is this kind of other data out there that can help us really understand that better. And it does feel a little bit like a rising tide. And so that's that's something that I think is important to recognize. But in terms of the seed round, really, that was meant to expand the platform and the pipeline that we built with our initial funding back from Laura Deming and Age One and True Ventures, who led around for us in early 2019. It's really saying like that initial $3 million or so is really to say like, does this work or is this crazy, right? Can we it's just a crazy idea.Ashley Zehnder: And that's what we really started to generate those first few animal studies that said, yes, actually we can find genes and compounds from this data that meaningfully affect not only human cells, but animal models of human disease. And now we're really expanding into new disease areas. We're looking at areas like fibrosis. We're looking at areas like pulmonary disease. We've got some really interesting data coming out of animal models of pulmonary hypertension with a compound that we found on our platform. We've got the collaboration with Novo Nordisk, which of the five genes that they tested in animals? We have one that has a significant obesity phenotype. So I mean, 20% hit rate on a novel target discovery in vivo is not bad, right? So we've gotten to the point now where repeatedly over multiple disease areas, we've seen that between 20 and 30% of our either compounds or genes are hits, which shows us that this is not only kind of a we got lucky in cardiac disease, but actually this is a process for enriching for important drug targets. And now it's a matter of really expanding the pipeline. We brought on a really experienced head of Therapeutics Discovery, Brian Burke, who spent 20 years at NIBR running very early discovery programs and then seeing programs go into the clinic.Ashley Zehnder: He worked on drugs like Entresto and then worked on a couple of startups after that. So he's kind of gotten both big pharma and startup experience, and his job at Fauna is to really look at the menu of things that we're presenting him from an early research and discovery phase and picking the winners and really figuring out how to take them forward and also killing the programs that are less exciting to him for a number of technical or practical reasons. So that's been really, really helpful to have someone come in truly from the outside and take a look at the science at Fauna and say this is as good or better as anything that I've worked on before. I'm really excited to work on this, and that's been kind of a nice external perspective on on the science and the pipeline at Fauna. So that's really what the $9 million is for. It's really expanding a lot of the computational expertise and and progress and Linda can talk a little bit about that, but also just expanding into new disease areas as well.Harry Glorikian: Understood. So, you know, on this show, like, I talk a lot about, you know, technology, data, and how it's all affecting health care, which this all fits into. But one of the things we talk about a lot is how crappy, terrible, I should use, you know, terrible, right, electronic health records are in the lack of interoperability between them. And Ashley, you actually wrote a paper.Ashley Zehnder: I did, yeah, veterinary medical records are just as bad, actually, veterinary medical records are probably a little bit worse, if it's possible.Harry Glorikian: And to be quite honest, I'm sorry, I just hadn't thought about Fifi or Rover and their...Ashley Zehnder: Their medical records.Harry Glorikian: EHR. Is like is the problem bigger, even, when it comes to functional genomics? I'm trying to think of like obtaining and storing and analyzing 'omics of different species. I mean, who's working on this? Is that part of the Zoonomia consortium? Right. I'm just trying to think it through, like, how do you get all this information and then look at it across all these different species. And at some point, you know, look looking at it against humans also.Ashley Zehnder: Yeah. I'll let Linda talk about the genomics side. I'll comment on sort of some of the validation, some of the externally curated data that Linda talked about. I think this is actually becoming a really important data set. It was a little bit of a slow burn to figure out how to get it and to curate it. But there are a lot of studies now coming out and not just your traditional model organisms, but naked mole rats and long lived rock fishes and primate studies and bats and all kinds of people looking at genomics and RNA seek metabolomics and proteomics across these species that have interesting phenotypes. The problem is, every one of those researchers really heads down on their own species of interest, right? Nobody's saying, oh, well, actually, we're seeing the same genetic signature in these bats that we're seeing in the naked mole rats that we're seeing in some of these long lived fish. Right. But that data is not in a very friendly format. So we were like originally we were like, okay, we're going to write some scripts, we're going to try to pull some of the stuff out of supplemental tables. It's going to be awesome. No, no, no. We have very highly trained curators who work on this data and bring it in. And we have a very standard pipeline and a process and a way to normalize the data across different studies and standard ontologies and ways to clean up this data in a way that it can be integrated with the genomics coming out of the platform. And that is a tedious and painful and ongoing effort to bring in all this data.Ashley Zehnder: Now, we have data from well over 330 individual studies, over 30 species. I think Linda, you told me it was like more than 800,000 gene entries at this point that's curated and that's kind of growing month over month. So now that's becoming part of our defensible moat, is that we've taken the last two or three years, again, slow burn, pulling all this data together in a way that it can be reused. And now we can turn a paper around and put it on a platform in a week or two. So we're kind of always scanning for these studies. But yeah, it's, it's, it's out there, but it's not always in a usable format without a lot of pain and effort. And so we've kind of put that pain and effort into getting that data in a place that we can use it. And then, of course, the comparative genomics is like a whole 'nother level of complexity.Linda Goodman: Yeah, so I can talk a little bit about how we do that within the comparative genomics community and how we've done that for Zoonomia. Because I referenced before that we like to do these sorts of studies to examine the genomes of hibernate ers and non hibernate and figure out what's different. And you'd think it would be a trivial question who is a hybrid nature amongst mammals? But it's actually not. And so along with our collaborators Alison Hindle and Cornelia Santer, as part of the Genome Project, Fauna tried to go through and categorize every every genome that was in Zoonomia. So we're talking about around 250 mammals for is it a hibernater, or is it not? And you'd be surprised how often it was digging through literature from the 1970s and someone would say, this animal is not often seen during the winter. So we think it hibernates and it's not always the most satisfying. And so it is an extremely tedious effort, but well worthwhile to go through and say this animal, I'm very sure, hibernates. This one, I'm very sure does not. And then there's this third category of animals that were unsure about we're going to remove those. And it's tedious, but you have to do that part, right? Because if you do the analysis with bad data, you're never going to find the genes that you want. And Linda, I remember you telling me when you were going through this very painful process, I think your threshold for being a perpetrator, quote unquote, was that you could drop your metabolism like 50%. Correct me if I'm wrong, and humans could go down to like 40 like in certain instances, like humans are almost there. You know, it's it's hard to know when there is only one paper about it, but certainly there are some really deep meditative states and humans and low oxygen environments where, you know, we're getting kind of close to the area where we might say that that's a hibernated, but certainly not the duration that you get out of hibernation. But it's it's it surprised me to see how close how much how much metabolic flexibility there really is when you start to look at it. Yeah.Harry Glorikian: Yeah. We've got to go talk to the monks.Linda Goodman: Absolutely. Absolutely. You know, we have that in mind. It sounds like an interesting travel experience. Yeah.Harry Glorikian: So I want to jump back for a second because. You guys don't necessarily have from what I have pieced together, the normal sort of like startup story. Right. First of all, you're an all female founding team, right? Highly unusual, right? Not something I see every day. You guys started at an accelerator program in San Francisco called Age One.Ashley Zehnder: Age One.Harry Glorikian: And then you moved to QB3 and the East Bay Innovation Center.Ashley Zehnder: Yep.Harry Glorikian: And then I think they helped you with some paid interns.Ashley Zehnder: Well, we got some from Berkeley. Yep, we did.Harry Glorikian: Yeah. And then you went through a SBIR grant.Ashley Zehnder: A couple of them.Harry Glorikian: From the Small Business Administration. And then a small business technology transfer grant from the Human Genome Research Initiative at NIH. Right.Ashley Zehnder: Yep.Harry Glorikian: I'm hopeful, hopefully my notes are all correct. Talk a little bit about the on ramp or infrastructure today for sort of seed stage startups like you. I mean, what were the most important resources?Ashley Zehnder: This is such an important conversation. I'm really glad you're asking this question. We had a call with a reporter from Business Insider yesterday who was talking to all three of us about this early founder ecosystems in biotech and sort of East Coast versus West Coast ways of starting biotechnology companies. Right. And that is a whole do a whole podcast on that, let me tell you. But I will say that there are a lot of resources for, let's call them founder led bio. Right. In the West Coast, which is kind of the buzzword these days, but people really supporting the scientists who originate the concepts and training them to be founders as opposed to assuming that you need to bring in an experienced CEO to run a company at this stage. Right. So I think we were very fortunate to meet Laura Deming at Stanford, who is one of the founding VCs. And longevity before that was a buzz word, right? She was one of the first longevity funds, literally Longevity Fund, and is really been a champion of founders, starting companies and really training founders to start companies who are deep science founders. So we started in age one. It was the first batch of age one. We're still very close to that cohort of companies doing interesting things from machine learning and image analysis through pure therapeutics development. And then Laura really helped us, her, her. We asked her later, like, why did you end up investing in us? She said, Well, the science was amazing.Ashley Zehnder: This is totally a field with so much promise. I just needed to teach you guys how to pitch. The science was there, right? So she helped me just how to pitch and how to use less science words in our pitches, which we're still working on to some extent. But then it was this balanced approach of taking in some venture money to really support the growth of the company, but balance with some of this non-dilutive funding for specific projects where it made sense and some of that was some of that in the early stage is validation, right? Having having funding through groups like NHGRI, having an early partnership with a company like Novo Nordisk, which provided also some non-dilutive funding for the company, really validated all of the science that we were doing because we were first time founders, because we're a little bit outside of the normal profile. For me, I don't feel weird being a female founder only because 80% of veterinarians are female. Like, I'm used to being in a room with all women. You go to a bio conference, it's not the same thing, right? So for us, we're just we are who we are. Right. But it's helpful, I think, to get some of that external validation and then really be able to use that to to start to build on programs and show progress.Ashley Zehnder: And then it becomes more about the data and the progress and what you can do with it. So that's a lot of how we started the company. There's I said there's a lot of support in the West Coast for this kind of thing. There's great programs like Berkeley Foreman Fund Talks, which I worked, which I was in as well, just about logistics around starting companies. There's a lot of good startup accelerators. I've got a really amazing all of us, how amazing a network of founders who we can reach out to on different. I got four or five different Slack channels of founders that I could reach out to for all kinds of advice. And usually it's always good to have a company that's one or two stages ahead of you, like talking to folks who IPO'd or something last year is is not as helpful as folks who recently raised a series B, right. And figuring out what those milestones look like and then particularly those that have taken mostly money from tech investors like we have all the lifeforce capital who led our last round is also has funded some very good therapeutics companies, Sonoma Therapeutics and Second Genome and other therapeutics companies as well. So I think it's it's helpful to see how people balance the needs of the companies at different stages in what you need.Harry Glorikian: But so do you guys think that you could have started Fauna ten years ago? I mean, did the support systems exist for starting a company like this?Ashley Zehnder: Well, no, for two reasons. We couldn't have started Fauna ten years ago. One is the data just simply wasn't in a place that the company was a tractable strategy. Everything was still too expensive and we had really shitty genomes for a few species at that point. And B, I think there really wasn't the kind of groundswell of support for deeply scientific technical founders to start their own companies and train them to be the kind of leaders they need to be to run those companies for a longer term. So I think it's a confluence of those things and being in an environment like Stanford that really encourages people to to try startups, it's not a crazy idea. Like people don't look at you like you're your heads backwards. If you start to start a company at Stanford, it's like, okay, cool. Like, when are you launching? You know.Harry Glorikian: I think it's the opposite.Ashley Zehnder: Yeah, exactly. Exactly. Like, why aren't you have a company yet? Whereas you know, a lot, many, many, many, many other places like that is seen as a very strange thing to do. So I think the environment plays a huge role. Yeah, for sure.Harry Glorikian: Yeah. I think between East Coast and West Coast too, there's.Ashley Zehnder: That's a whole, we should have a whole 'nother podcast on that.Harry Glorikian: Yeah. Yeah, exactly. Well, I live here and I was I was born and raised on the West and I remember there and I came here and I was like, Oh, this is where you are not in Kansas anymore. Like, this place is different. So, I mean, I'm hoping that the East Coast is actually embracing risk a little bit more and sort of stepping out on the edge. But it's really slow. They don't call it New England for nothing. So. But, you know, it was great having you both on the show. I this was great. I we covered a lot of ground. I'm sure people's heads are spinning, thinking about, you know, you know, different animal species and how that's going to play into this. And I mean. It really does sound like I know we have to do the hard work, but there's a lot of computational effort that has to go on here to sort of. Make sense of this and bring it all together and align it so that you can be looking at it properly and make the right decisions going forward.Ashley Zehnder: Yep. Millions of data points coming together to find drug targets for sure.Harry Glorikian: So thanks for being on the show. And you know, I wish you guys incredible luck.Ashley Zehnder: Thanks, Harry, so much. This was fun.Linda Goodman: Thanks for having us.Harry Glorikian: Thanks.Harry Glorikian: That's it for this week's episode. You can find a full transcript of this episode as well as the full archive of episodes of The Harry Glorikian Show and MoneyBall Medicine at our website. Just go to glorikian.com and click on the tab Podcasts.I'd like to thank our listeners for boosting The Harry Glorikian Show into the top three percent of global podcasts.If you want to be sure to get every new episode of the show automatically, be sure to open Apple Podcasts or your favorite podcast player and hit follow or subscribe. Don't forget to leave us a rating and review on Apple Podcasts. And we always love to hear from listeners on Twitter, where you can find me at hglorikian.Thanks for listening, stay healthy, and be sure to tune in two weeks from now for our next interview.

Columnist Mary Jane Hampton looks at how pets have the potential to significantly improve the lives of seniors in this week's healthcare hacks. Plus, what happens if you run into problems and need help looking after a pet?

Dr. Becca Levy's research explores psychosocial factors that influence older individuals' cognitive and physical functioning, as well as their longevity. She is credited with creating a field of study that focuses on how positive and negative age stereotypes, which are assimilated from the culture, can have beneficial and adverse effects, respectively, on the health of older individuals.Dr. Levy's book, Breaking the Age Code: How Your Beliefs About Aging Determine How Long and Well You Live is available now!Learn more about Dr. Levy at: https://ysph.yale.edu/profile/becca_levy/.Support the Show - Become a Patron!Help us grow and become a Patron today: https://www.patreon.com/smartpeoplepodcastSponsors:Fast Company Press - Visit fastcompanypress.com/podcast for a no-charge manuscript evaluation or publishing consultation.Golden Poppy Herbs - Get 20% off your entire order by going to https://goldenpoppyherbs.com/smartpeople. Use promo code SmartPeople20.

SHR # 2854:: O-LIVE Longer: The Olive Oil Hunter - T.J. Robinson - Olives and their precious oil have been around since the 8th millennium BC. The oil has been used in food, cosmetics, pharmaceuticals, soaps, and fuels for traditional oil lamps. Olive oil has also been used in religious ceremonies. Its popularity has caused an entire industry from adulterating olive oil by adding oils like canola oil and soybean oil and selling it as 100% olive oil. The process of making 100% olive oil also plays a large role in the quality of the final product. we'll learn more abut this ancient oil and how to steer clear of fakes. Get your first bottle worth $39 for $1. Go to http//shrnetwork.biz/getfresh today.

Did you know that the American Kennel Club lists the average life expectancy of about 10 to 12 years? This number can go up or down for a variety of factors including health, genetics, diet, and environmental factors. Smaller dogs like toy breeds tend to live longer while giant breeds like the Great Dane and Deerhound live much shorter lives, sometimes less than eight years. Any way around it they don't live nearly long enough, do they? Read More: Dog Aging Study Support our work: Donate Now

Eating meat could help you live longer. That's according to research, but the results appear to have a major flaw.   Dr. Matthew Nagra joins “The Weight Loss Champion” Chuck Carroll on The Exam Room LIVE to talk about the findings and how he believes researchers missed the mark by such a wide margin. As he points out, the data could also be interpreted to show another major carcinogen could also extend your life. But nobody is arguing that smoking is the key to longevity.   Dr. Nagra also answers questions sent into The Doctor's Mailbag.   - Is chicken a healthier option? - Are lean meats harmful to heart health? - Can chocolate increase cholesterol? - Does sugar increase cholesterol? - Many more!   Join Chuck and experts for The Exam Room Live Wednesdays at 12 p.m. ET/9 a.m. PT on Facebook and YouTube.   — — — Dr. Matthew Nagra Twitter: https://twitter.com/drmatthewnagra Instagram: https://www.instagram.com/dr.matthewnagra Facebook: https://www.facebook.com/dr.matthewnagra — — — Chuck Carroll Instagram: https://www.instagram.com/ChuckCarrollWLC Twitter: https://www.twitter.com/ChuckCarrollWLC Facebook: http://wghtloss.cc/ChuckFacebook — — — Physicians Committee Instagram: https://www.instagram.com/physicianscommittee Facebook: https://www.facebook.com/PCRM.org Twitter: https://www.twitter.com/pcrm — — — 21-Day Vegan Kickstart App iOS: https://bit.ly/VegKStrt-iOS Android: https://bit.ly/VegKStrtAndrd Web: https://www.pcrm.org/kickstart — — — Barnard Medical Center Appointments https://bit.ly/BMCtelemed 202-527-7500 — — — Share the Show Please subscribe and give the show a 5-star rating on Apple Podcasts, Spotify, or many other podcast providers. Don't forget to share it with a friend for inspiration!

Years of research on calorie restriction and longevity mean we know that limiting how…

This episode will make you feel COMPLETELY different about getting older.

Welcome to Simple Joe. I'm glad you're here. Email me at joe@thesimplejoe.com or send me a text at 513.399.6468. Just say hi, I would love to hear from you. You can get Simple Joe T-Shirts and other cool stuff at thesimplejoe.com/store Check out what I'm reading at thesimplejoe.com/reading If you share the show on Facebook, Twitter, or Instagram, please use #simplejoeismyfriend; you might get a free t-shirt!

Check out our sponsor: ButcherBox: Sign up at ButcherBox.com/impact For most of us, when we think of melatonin, the first thing we think of is “a chemical to make you feel sleepy”.And while it's true that melatonin plays a critical role in governing our circadian rhythm, it turns out that melatonin is also one of the most powerful antioxidants produced in the body.This is a huge deal when it comes to disease prevention, as oxidative stress and inflammation are primary causes of some of the deadliest and most common diseases known to man.In today's episode of Health Theory, Dr. Roger Seheult breaks down the science of melatonin, vitamin D, circadian rhythm, and much more.So whether you've been having trouble sleeping, are worried about inflammation and disease prevention, or just want to brush up on your biochemistry, then I promise you'll get something beneficial out of today's episode.SHOW NOTES:00:00 | Introduction00:52 | Get More Sunshine16:03 | What Is Oxidative Stress?27:46 | The Physiology of Covid33:03 | Optimize Your Circadian Rhythm44:30 | The Double Slit Experiment49:09 | Meat vs PlantsQUOTES:“One of the things that we've discovered as scientists is that the mind and the body are a lot more connected than we thought they were.” [09:30]“I think it would be a mistake to say that while I'm taking my vitamin D supplementation, I don't need to go out into the sun.” [11:18]“We see diabetes associated with obesity, obesity with inflammation, diabetes with oxidative stress. So we do see them correlate - it's hard to tease them out.” [15:45]“I can't stress this enough: Alzheimer's disease, autism, diabetes - a lot of these diseases that we see in society have been tied to mitochondrial damage from reactive oxygen species. It's really important.” [20:50]“We have technology today, that allows us to eat 24 hours a day. We have technology today that we can turn night into day if we want, we can work 24/7. There's gamers that do that, they go straight for 48 hours and they die. And so what we're finding out is that technology, even though it allows us to do certain things, they may not be optimal.” [37:43]Follow Dr. Roger Seheult and MedCram:Website: https://www.medcram.com/ Twitter: https://twitter.com/medcramvideos Instagram: https://www.instagram.com/medcram/ LinkedIn: https://bit.ly/3Dl291B YouTube: https://bit.ly/3JJGX7M

Check out our sponsor: ButcherBox: Sign up at ButcherBox.com/impact For most of us, when we think of melatonin, the first thing we think of is “a chemical to make you feel sleepy”.And while it's true that melatonin plays a critical role in governing our circadian rhythm, it turns out that melatonin is also one of the most powerful antioxidants produced in the body.This is a huge deal when it comes to disease prevention, as oxidative stress and inflammation are primary causes of some of the deadliest and most common diseases known to man.In today's episode of Health Theory, Dr. Roger Seheult breaks down the science of melatonin, vitamin D, circadian rhythm, and much more.So whether you've been having trouble sleeping, are worried about inflammation and disease prevention, or just want to brush up on your biochemistry, then I promise you'll get something beneficial out of today's episode.SHOW NOTES:00:00 | Introduction00:52 | Get More Sunshine16:03 | What Is Oxidative Stress?27:46 | The Physiology of Covid33:03 | Optimize Your Circadian Rhythm44:30 | The Double Slit Experiment49:09 | Meat vs PlantsQUOTES:“One of the things that we've discovered as scientists is that the mind and the body are a lot more connected than we thought they were.” [09:30]“I think it would be a mistake to say that while I'm taking my vitamin D supplementation, I don't need to go out into the sun.” [11:18]“We see diabetes associated with obesity, obesity with inflammation, diabetes with oxidative stress. So we do see them correlate - it's hard to tease them out.” [15:45]“I can't stress this enough: Alzheimer's disease, autism, diabetes - a lot of these diseases that we see in society have been tied to mitochondrial damage from reactive oxygen species. It's really important.” [20:50]“We have technology today, that allows us to eat 24 hours a day. We have technology today that we can turn night into day if we want, we can work 24/7. There's gamers that do that, they go straight for 48 hours and they die. And so what we're finding out is that technology, even though it allows us to do certain things, they may not be optimal.” [37:43]Follow Dr. Roger Seheult and MedCram:Website: https://www.medcram.com/ Twitter: https://twitter.com/medcramvideos Instagram: https://www.instagram.com/medcram/ LinkedIn: https://bit.ly/3Dl291B YouTube: https://bit.ly/3JJGX7M

We've all heard the saying that our genes determine our destiny.We've all heard the saying that our genes determine our destiny. If your parents died in their early seventies, that means you are more likely to die in your seventies. A family history of chronic disease means you're more likely to get it.Even obesity is blamed on our family tree. Well, our guest today, Dr. Kara Fitzgerald says it's not genetics that determines our age and level of health, it's our epigenetics. Research shows by using diet and lifestyle modification, we have the innate ability to reverse our biological age.Dr. Fitzgerald is a doctor of naturopathic medicine and an Institute for Functional Medicine Certified Practitioner.She's the lead author and editor of case studies and integrative and functional medicine and became the first-ever recipient of the Emerging Leadership Award from the Personalized Lifestyle Medicine Institute, as a leading voice in the intersection of nutrition epigenetics and aging. Her new book is called "Younger You: Reduce Your Bio Age and Live Longer and Better."

In this episode of What You're Craving, Molly welcomes Jessie Inchauspé (a.k.a. Glucose Goddess) to talk all things monitoring glucose, how to control glucose spikes, the consequences of high glucose levels in our body, and how to manage it all without giving up the foods we like. High glucose affects our mental health as well as our physical health, and Jessie talks all about it in this conversation. In addition, she shares the easiest and most uncomplicated hacks to manage your glucose levels when ingesting a variety of foods. Consuming a high-protein/high-fat breakfast and combining a protein source with a carbohydrate source, for example, are two of these hacks. Jessie also talks about the best options for snacks, juices, smoothies, and how to implement these habits into our daily lives. Tune in! Episode Quote “Every time we eat, if we're eating starches or sugars, they break down into glucose as we digest them, and glucose is great, it's our bodies' primary energy source and every cell in our body needs it for energy. Things start getting tricky when you experience a glucose spike, which is too much delivery of glucose, too quickly in your body.” – Jessie Inchauspé Key Highlights CGM (Continuous Glucose Monitor): what is it, how does it work, and Jessie's experience with this kind of monitoring data; How glucose spikes affects mental health besides being an important cause of skin problems; Lack of sleep is one of the most important aspects of our routines that influence glucose levels; Hacks to keep our glucose levels steady (10 principles); Jessie shares the best options for snacks, fruits, juices, smoothies and how to combine types of foods not to spike glucose levels; What kind of health issues we may have when glucose levels are high and how to implement some of the hacks into daily life. About Jessie Inchauspé Jessie Inchauspé is on a mission to translate cutting-edge science into easy advice to help people improve their physical and mental health. She's the founder of the wildly popular Instagram account @GlucoseGoddess, where she teaches hundreds of thousands of people about healthy food habits. In her first book, Glucose Revolution, Jessie shares her startling discovery about the essential role of blood sugar in every aspect of our lives, from cravings to fertility, and the surprising hacks to optimize it while still eating the foods we love. Connect with Jessie Inchauspé Instagram: @GlucoseGoddess Book: Glucose Revolution by Jessie Inchauspé About Molly Carmel Molly is a leading addiction and eating disorder therapist and the founder of the Beacon Program, which offers individual and group solutions to help people break free from their destructive relationships with food and dieting. She is also the author of ‘Breaking up with Sugar' and the host of ‘What You're Craving' Podcast. Connect with Molly Want to spend MORE time together? Me too! Here are all the ways: Instagram: @mollycarmel Facebook: Molly Carmel YouTube: Molly Carmel Free Mini Masterclass: mollycarmel.com/signup Breaking Up with Sugar Course: molly-carmel.mykajabi.com/buws-course Breaking Up with Sugar Facebook Group: facebook.com/groups/buwsbook Monthly Group Coaching: mollycarmel.com/coaching-with-molly Weekly IntenSati Spiritual Fitness Class: mollycarmel.com/intensati

Author of ‘The Expectation Effect,’ David Robson, joined Bob Sirott to discuss how the way you think could help determine certain life events, such as how fast you mentally age and how long you could live. They also talked about self-fulfilling and self-inflicting prophecies.

In a day and age when it feels like there are drugs for everything—from restless legs to toenail fungus to stage fright—it's strange the drug industry has almost completely ignored one of our most important organs: our ears. Given that 15 percent of people in the U.S. report at least some level of hearing loss, you'd think drug makers would be doing more to figure out how they can help. Well, now there's at least one company that is. Cambridge, Massachusetts-based Decibel Therapeutics went public in 2021 to help raise money to fund its research on ways to treat a specific form of deafness caused by a rare genetic mutation. Decibel is testing a gene therapy that would be administered only to cells in the inner ear and would provide patients with a correct, working copy of the otoferlin gene, which is inactive in about 10 percent of kids born with auditory neuropathy. Harry's guest this week is Decibel's CEO Laurence Reid, who explains how the company's research is going, and how Decibel hopes to make up for all those decades when the pharmaceutical business had basically zero help to offer for people with hearing loss.Please rate and review The Harry Glorikian Show on Apple Podcasts! Here's how to do that from an iPhone, iPad, or iPod touch:1. Open the Podcasts app on your iPhone, iPad, or Mac. 2. Navigate to The Harry Glorikian Show podcast. You can find it by searching for it or selecting it from your library. Just note that you'll have to go to the series page which shows all the episodes, not just the page for a single episode.3. Scroll down to find the subhead titled "Ratings & Reviews."4. Under one of the highlighted reviews, select "Write a Review."5. Next, select a star rating at the top — you have the option of choosing between one and five stars. 6. Using the text box at the top, write a title for your review. Then, in the lower text box, write your review. Your review can be up to 300 words long.7. Once you've finished, select "Send" or "Save" in the top-right corner. 8. If you've never left a podcast review before, enter a nickname. Your nickname will be displayed next to any reviews you leave from here on out. 9. After selecting a nickname, tap OK. Your review may not be immediately visible.That's it! Thanks so much.TranscriptHarry Glorikian: Hello. I'm Harry Glorikian, and this is The Harry Glorikian Show, where we explore how technology is changing everything we know about healthcare.These days, it feels like there's a medicine for almost everything.There are drugs to calm your restless legs. There are drugs to treat fungal infections under your toenails or fingernails. There are even drugs to calm down performers who suffer from stage fright.So it feels odd that the drug industry has almost completely ignored one of our most important organs: our ears.15 percent of people in the U.S. report at least some level of hearing loss, so you'd think drug makers would be doing more to figure out how they can help.Well, now there's at least one company that is. It's a six-year-old company based in Cambridge, Massachusetts called Decibel Therapeutics.Decibel went public in 2021 to help raise money to fund its research on ways to treat a specific form of deafness caused by a rare genetic mutation. It turns out that in about 10 percent of children who are born with auditory neuropathy, the problem is a mutation in the gene for a protein called otoferlin.It's involved in the formation of tiny bubbles or vesicles that carry neurotransmitters across the synapses between the inner hair cells that pick up sound and auditory neurons in the brain.Decibel is testing a gene therapy that would be administered only to cells in the inner ear and would provide patients with a correct, working copy of the otoferlin gene.Otoferlin wasn't even discovered until 1999. So the fact that there's a drug company working to correct mutations in the gene for the protein is a great example of how genomics is enabling big advances in medicine.My guest today is Decibel's CEO Laurence Reid.And in our conversation he explained how the company's work is coming along, and how Decibel hopes to make up for all those decades when the pharmaceutical business had basically zero help to offer for people with hearing loss.Harry Glorikian: Laurence, welcome to the show. It's great to have you here.Laurence Reid: Yeah. Hey, good morning, Harry. Great to see you again. Thank you. Thanks very much for the opportunity to join you. I'm looking forward to it.Harry Glorikian: Yeah, I mean, we've known each other for, my God. I remember. Like, I want to go back in time to Warp or one of those companies way back when you were there.Laurence Reid: Like ten or 15 years ago, I think I think we're both compressing our compressing our memories. I think it was a while before that. But, you know, you've been a student of personalized medicine, of course, a leader. Those ideas and I know a lot of those ideas for me started at least personally when I was at Millennium. And I think we were pretty you know, there was a lot of fantastic thinking that some of what was ahead of where we really were technologically. But I think that's when you and I first met. So, no, it's great to reconnect.Harry Glorikian: Yeah. And now you're CEO of a company called Decibel, which is ironic because I remember when the company literally was coming out, they called me to help them think through diagnostics.Laurence Reid: Oh, interesting. I wasn't aware of that. Yeah, the company got incubated at Third Rock and got launched in 2016. So we're about six years old now. And, you know, we believe that the time is is now for sort of molecular innovation coming to hearing loss. And I'd love to talk more about that. But the diagnosis remains, there's an interesting, there's almost a dichotomy because at least in the in the Western world, we put our babies religiously through a hearing test within 24, 48, 96 hours of being born. And then and then beyond that, like we sort of like almost, we don't quite ignore it, that would be unfair, but the caliber of follow up care, never mind when you're our kind of ages, is really poor. So we're like we're really good out of the gate. And then after that and part of that is diagnosis. I mean, we think a lot about it, which, you know, you would love, is trying to think about improved molecular diagnostics, particularly with respect to the genetic components of hearing loss. So love to talk more about that.Harry Glorikian: Yeah. I mean, you know, you were talking to Kevin Davies on on another show. I mean, I think you mentioned you said something like "Hearing is a backwater of the pharmaceutical industry." And most of the focus is is what I would call a device, not necessarily a drug. So, you know, if we let's I mean, starting there, where do you see or how do you see that changing? And, you know, how have genomic tools and and these things made a difference in the direction that we're going. And I think that's what Decibel was sort of formed around, if I remember correctly.Laurence Reid: Yeah, no, you're exactly right. But those are, those are the central questions. So where we are today is there are, so, so, both. And we think about both hearing loss and balance disorders, because they're both mediated by evolutionarily related organs that sit inside inside the inner ear. And, you know, the hearing loss afflicts literally hundreds of millions of people around the globe at all ages. It can come on, you can whether it's congenital or it's sort of later in life or noise induced. So it's a massive unmet need. And, you know, and there are no approved therapies. So it's it's a field of medicine today that is that is completely served, to the degree it is served, by assistive devices, namely hearing aids and then cochlear implants. And there are no approved therapies. And I think the pharmaceutical industry has been really, is just not invested in the field at all. Astellas works with our friends at Frequency and has been committed and a couple of other big companies have sort of dabbled and then and then exited. Translation has been has been a challenge. We should talk about that preclinical work not really replicating once you get to you know, human beings. And so it's been a quite a difficult field for for many years. And and so the pharmaceutical industry has really not dived in and, you know, in Third Rock was really incubating decibel which is how they how they start companies. It was one of their ones that was was a slow burn.Laurence Reid: And they had they looked at assets out of one or two pharmaceutical companies and were really trying to get their heads around, is the time really now. And they they pulled the trigger in 2016 and went into it with a belief that that molecular innovation was coming and is coming and that that would that would give rise to therapies. So here we are six years later. And the playing field, as I like to say, is really, you know, dominated by small companies. We like to think about Decibel as a leader there, but there are other companies doing fine science, but they're small companies. And but that's going to change. It has to change. And it's going to be exciting from many aspects. When it changes, it affects how you build a company, when pharmaceutical companies are sort of watching, but they're not committed and they're not they're certainly not investing yet. But I think that's going to change. And I think we're going to see it change, I don't know, in the next couple of years. And I think 5 to 10 years from now, all the major pharmaceutical companies would have to be playing in this because, you know, there's the aging component, there's the cognitive health later in life. You could talk more about the specifics of why hearing is so important to our existence as human beings. And that's really not just a quality of life issue. And that's going to change. To have that happen.Harry Glorikian: That's why I was going to I was going to say I mean, I think if I remember correctly and it was fascinating to me when I went into Decibel, like, you know, when it was first getting started and how it was having conversations, it was like the number of people that are losing, you know, certain parts of their hearing earlier in life because of all the headphones and how loud they listen to things and so forth, was staggering. And then the economic impact of that was even more staggering. And so you would think that it's not just the pharma industry that would be interested, but anybody that—-like I've got my AirPods in now. So I mean, Apple should be interested.Laurence Reid: Those guys, those guys are working around the field. Bose, of course, a fine Massachusetts company with some of the best sound equipment. They've been investing in the hearing aid technology field for in recent years and have just launched a new generation of technology under that umbrella and come out with some pretty sophisticated marketing, trying to really get people to think about the quality of their hearing and why it's important. And so, as you say, so new people coming at it despite perhaps their contributions to it. And so, you know, so I think I think that's really very, very interesting. And but it is now devices, as you say. It's devices. So today, you know, a lot of it is treated nominally with hearing aids and then for very severe forms, particularly in in in young kids, but in adults as well. There's a technology which has been around for about 20 years now, known as a cochlear implant, where you have a surgical implantation of a very sophisticated device into your cochlea. And essentially it essentially hard wires, really a microphone directly to the onto the auditory nerve.Laurence Reid: And so there's a device inside your head and then there's a detection device that is visible outside. But both of these we view as assistive devices. And I mean, with some of the things that we're thinking about for molecular therapies, you know, we really think we can be disease modifying. And the devices are, they're an attempt to sort of palliate, effectively, the manifestations of hearing loss. They don't work 24/7 because they can't and kids in particular hate wearing them. But, you know, our parents hate wearing them as well, particularly the hearing aids. And so the compliance is very poor. But I think more importantly, they can only be so effective, and particularly if you're very severely deaf, the difference between that status and, you know, what the kid next to you in the classroom is hearing and picking up and how that's affecting their development is really massive and to me is one of the big drivers certainly why I got excited about the field personally.Harry Glorikian: Oh yeah. I mean, you know, if you're in a crowded restaurant and you can't hear the person across from you, there's all of a sudden it changes the entire dynamics of what's going on. I mean, that you know, that said, I think if my wife could implant a microphone that was directly wired into my brain, she would probably take advantage of that to make sure I hear everything.Laurence Reid: And hard wired up straight into her larynx. And then then everything would be would be beautifully aligned. Yeah, I know. It's really interesting. So my beloved mother is 84 and you have a one on one conversation with her and it's fine. You know, it's absolutely it's completely normal, like you and I chatting or talking to a 20 year old. But you put her in a crowded restaurant and it's very hard for her to participate at all. And so it's a really interesting. So on one level that's trivial, right? It's a night out in a restaurant. But it's indicative of the challenge. So I always think most easily comes to me with thinking about congenital deafness and then deafness or loss of hearing in in older people. But that restaurant is sort of an analog for in the case of the older people losing, you know, we talk a lot about connection, losing connection with their loved ones or their coworkers or their family. And, you know, hearing loss is the number one risk factor in cognitive decline later in life. And nobody is suggesting it's necessarily causative. But that loss of connectivity clearly in some way is contributing to, you know, to a cognitive decline. And I think that's really the way to think about it. For me, I think about hearing loss as why, why does it matter? And it's not because I think it's, if you haven't dealt with it, you probably think about it in terms of a social discourse. But actually why it really matters is the impact on, I use the phrase cognitive health, which is probably not a phrase of professional would use. It's really how is your overall ability to interact with people, to process information and and to share it? And if you're disconnected, it's clearly contributing to that lack of of of interaction and ability to, you know, to have discourse with our with our with our families. And so you see that. Pivoting to loss of interactions later in life. And then for a kid.Harry Glorikian: And how it affects the economy. I mean, if you're not going out to dinner or you're not or you don't hear everything at work or things like that, I think the impact is is dramatic. But you know how many I know you guys are working on different therapeutic approaches to solve this problem. So, you know. How many different forms of deafness right now, or maybe balance disorders, are monogenic or or caused by mutations of a single gene that, say, we can get in there and do something about it, because I think that's where you guys are starting.Laurence Reid: That's where we're starting. And that's exactly the right way to think about it. So let me let me step back and then I'll answer your specific question. So the strategy that we've taken and other people have different views of this is really that the most robust understanding in 2022 of the molecular etiology of any form of hearing loss is, is that it's driven by overtly by monogenic conditions. So two mutated genes inherited from mom and dad that good old recessive genetics and that therefore we're able to understand precisely what's causing it and we're able to understand the impact of that of a child born with bi-allelic mutations in the otoferlin gene for example. And and the promise of gene therapy is the ultimate to put back a a functioning copy of the gene very early in life and put a child back to a physiological state of of hearing that mimics the kid down the street. And that's and that's the ambition. And what we think will that will enable is both these modifying treatments, maybe even cures for for those sections of the population. But it'll teach us about how to do gene therapy safely in the ear. We think the ear is a wonderful organ in which to do gene therapy. We should probably talk about that in a moment.Harry Glorikian: Yeah, absolutely.Laurence Reid: But that over time, the Holy Grail. So as you get into the bigger populations, it's a classic, you know, genetics and environment, viruses, noise, lots of chemicals or lots of things  that damage areas over the course of life. And we just naturally lose the sensory hair cells in areas over the course of life. Everybody approximately linearly is losing that, that sensitive and that sensitivity. So eventually you hit a threshold and we all suffer from some form of hearing loss or balance, you know, lack of equilibrium as we get to be a little bit older and. For for many different causes. So the Holy Grail is can we really have regenerative medicines that regenerate the sensory the sensory hair cells, as they're called, in the inner ear, potentially as a treatment for hearing loss or balance disorders. And so the way we think about this is our strategy is really to to start with the monogenic forms of hearing loss have a chance for very clear diagnosis, driving, very precise clinical trials, driving potentially therapies that are directly addressing mechanism and with very high potential molecular upside. And to build from there into a pipeline of gene therapies that will start to go into broader populations, populations of much older people, and that will be gene therapies that are regenerative medicine. So that's our sort of long term vision of how this will how this will evolve. But it's starting with the monogenic conditions which which are which are rare diseases, orphan diseases by all definitions. And I think for the reasons that rare diseases have been such an intellectual driver of our industry in the past 20 to 30 years, is because you can link mechanism and etiology and a potential molecular cure in a very linear fashion. But it teaches you so much about how to manipulate an organ and how to develop therapies that eventually will treat broader populations.Harry Glorikian: Yeah. Laurence, you need to move faster, because I think I went to one too many rock concerts when I was younger. And, you know, I could tell you that.Laurence Reid: I had friends, when I was in high school who were who were into certain, you know, I hated heavy metal when I was a kid, but I had friends and they would come back and they'd been to a concert and they'd they'd stuck their head inside the speaker and they they couldn't hear for like a day or two. And I, I think back to those I worry about where those guys are now because they're hearing I'm sure they're otherwise.Harry Glorikian: Yeah. I mean, when you're when you're when your ear is ringing like a day afterwards, you probably recognized that was probably, it was a lot of fun at the time. But you pay for it later. But but stepping back, though, even if we were able to match every form of deafness to a specific genetic cause. Right. Very few infants or children get the kind of tests that would be needed. Like how widely available are these genetic tests for the hearing neuropathies today or.Laurence Reid: Oh, it's. I'm sorry. Go ahead.Harry Glorikian: No, no, no, go ahead. Because that would be my first question.Laurence Reid: It's the minority. And so by definition and I appreciate you've worked and thought a lot about this over the last years. You know, good diagnosis is is gating to everything that can follow. And so part of our broader I mean, at some level actually even step back from molecular diagnosis, which I know is where you'd want to go, that just overall how we manage hearing how is is almost rudimentary compared to how we think about about our eyes for example. And just I had my annual physical a couple of days ago and and a new physician and and the doctor was like, oh, you know, you go and get your eyes tested on, on an annual basis and which I do. And we talked about all the the good things that are cutting edge, you know, ophthalmologists does these days to look at your optic health. And then I was like, you know, the real question you should be asking me is, when did I get my hearing tested? And but when did you last get. We just we just it just doesn't it's just not part of adult health care in a routine way unless you get really I mean, my wife and I joke about it occasionally. I'm like, oh, well, let's go together and get our hearing tested.Laurence Reid: Not that, not that it's at all funny, it's not. It's a serious issue, but it's just not part of routine health care for helping adults think about about how how they manage their health. So. So we sort of we start with a, a broader set of educational issues. And then and then we dive down pretty quickly into how do we educate people about about the need and potential power of molecular diagnostics for children who, when we begin to figure out that they're hearing is developing, you know, in the early either days or early years of their life and as as in in the developed world, most children have a basic hearing test, you know, within hours of being born, literally, often while they're still in the hospital. And it's like, you know, in many, many places they catch them while mom is still, you know, literally in the hospital and and they do a basic hearing test so we can catch a lot of it like that. If it if you start if the hearing degenerates after that, it is still very challenging for that to get properly understood and picked up and diagnosed and managed even in, you know, developed cities and, you know, in the United States.Laurence Reid: And the the ability to to reflex to molecular testing is is very variable. If you talk to our our audiology team, it starts to be very dependent on which city do you live in and what's the ability? I mean, we're sort of privileged in Boston, Mass Eye and Ear is obviously one of the world's leading hospitals. But but how do you get from a an early "Yeah there's an issue here" to any form of molecular. What that path looks like of your pediatrician driving you to real audiological analysis, driving you to a molecular diagnosis. It's a pretty fraught path. You think about it in in in cities like Boston. Fair enough. And aren't we privileged to live here? We're lucky to live here from that perspective, but it's very heterogeneous. And so part of our work is really we have a collaboration with our friends at Invitae, part of which is trying to just it's almost educational. It's offering a free genetic testing service for important genes related to your hearing health. But part of the purpose is, is educational, really.Harry Glorikian: Yeah. Yeah, I was going to I was going to ask about that. I mean, in making it available, I mean, this is somewhat of a crusade, right, to educate people and get them on board, right. Because if you just don't know what's available, you may not think about it for your child. And if a parent knows they can help their child, I think most parents would go out of their way to do something positive. But just for everybody who's on the phone, you know, can you walk us through an example of, let's say, a single gene mutation can cause deafness? I mean, maybe you can concentrate on the example of, I think it's otoferlin, if I'm saying correctly, which you know, basically, if I've understood it correctly, it's the formation of the synaptic vesicles that carry neurotransmitters across the synapse, which is very, very tiny. And if the hair pulls away just enough, you start losing that ability to hear at that level because the chemical can't jump across to make that connection, which is, I think what's happening to me as I get older.Laurence Reid: Yeah. Very good. Yeah. And I'd love to talk about otoferlin. So otoferlin is our first program where we and other people are thinking about this as well. Our friends are also are working hard on this problem as well. But it's the vanguard program for Decibel and the field in terms of gene therapy for modern forms of hearing loss. And so obviously, we we know the gene that causes this particular subset of severe hearing loss. The children are born profoundly deaf. They really have almost no no signaling capability whatsoever. Despite that, when you study their ears and when you look at animal animal genetic models of the condition, the ear, functionally, structurally appears to be normally constituted. So what you see start with a belief that we may be able to instate normal hearing in these people by in these children, by, by by providing a a wild type, a normal copy of the gene. And there are other forms of of genetic hearing loss where by the time the kids are born, the children are born, their ear has not developed properly, structurally and functionally. And I think that's a much harder problem and may be impossible to to solve postnatally. So so as we think about areas where we think we can have an impact with the first generations, we're looking for clear genetics. We're looking for an ear that appears to develop normally and in which we therefore have the chance to instate normal hearing. Otoferlin is a calcium sensor and it functions at the interface between the hair cells in the cochlea, the inner hair cells, as they're called, which are the cells that transduce... Sound is effectively a mechanical signal. It comes to us as a sound wave, and it disturbs structures and eventually molecular structures inside your inner ear and creates a molecular signal that is transmitted by the hair cell through the synapse. As you say, to the auditory nodes, there's a direct interface between these cells that are that are detecting the sound wave into the into the auditory nerve. And if you lack otoferlin your calcium sensing functionality and that synapse is not present and and there's essentially no signal. So we measure this with something called an auditory brainstem response, which is a test you could run in a human or an animal. And there essentially it's a flat line, which from a from a restoration of a normal signal, it's a really excellent clinical endpoint because we're going to, we hope, instate, a signal, a quantitative signal with quantitative richness as well, that we're going to be able to measure relatively early after we administer our therapy. But the children have this is what we call an auditory neuropathy. They have no ability to signal from the cell into the brain. And as I say, the structures appeared to be intact. And what we know is that in an animal, if you create an animal model of this genetic animal model, that we can go into that now with DB-OTO, as we call it, which is which is a adeno associated virus vector to to basically deliver a normal form of the gene. And we can do that within weeks of this mouse being born. But interestingly, we could also go to those animals as long as a year after they're born, which which for a small furry animal is is about half of their life.Laurence Reid: So it's a big piece of their life. And and we can go in we can intervene at that at that one year point and still rescue the phenotype. So the is structurally intact. And when we provide the signaling molecule, we fairly quickly instate a normal signal. So that's that's exciting. Right. And A), it's a fantastic signal to measure in an animal. B) it gives us a lot of optimism that if we can get the gene to the right cells and get it turned on, then decent chance to to to solve to solve the signalling problem. So that's sort of our reason to believe. And actually maybe the last component, and then I'll breathe, is we think the ear is, is a fantastic place for gene therapy broadly because your inner ear is this tiny enclosed compartment. So we need a surgical route to get there, but we can then go directly to the site where one is trying to elicit a molecular effect and deposit a tiny amount of drug compared to what's required -- three or four orders of magnitude less drug than is required for systemic gene therapy -- directly at the site where we're looking to elicit the biological effect. And then almost none of it leaks out into the into the systemic circulation. So the ear, we think, is a fantastic order or organ for gene therapy, and we think we know some great genes to go after us, our first generation.Harry Glorikian: Yeah. I mean, you know, whenever if if people have followed any type of gene therapy, like the eye has been in optimal place to sort of start with. And so, you know, I think you guys are learning from what has been done in ophthalmology to sort of transition this to the ear, which, you know, I always say to people like we always start on the outside because it's a lot easier and then we then we figure out how to go deeper in because it's a lot harder. But, you know, what kind of results are you seeing so far when you transfer genes into, maybe nonhuman primates.Laurence Reid: Yeah. Yeah. No. So we've just in the last year or two, transitioned from rodent studies to non-human primates. You are correct that the characteristics of the ear that make us so excited about the possibility here, a lot of them are very much learning from why the eye has been really such a primary site of our efforts in gene therapy in the last ten years or so. And so as we move from small animals to larger animals to human beings, we start with, as I mentioned, genetic rodent models that we can knock genes out in the mouse that replicate the human genetics. The ear, it turns out, is it is evolutionarily highly conserved. So the the ear of a rodent is a lot smaller than than your ear in my ear. But structurally and molecularly and cellularly it's very analogous. And we can come back to your point about genomics and how it's opened up our understanding of these cells. But nonetheless, the basic structure and physiology is highly conserved from from lower mammals to to higher mammals. So so we start with genetic models that we can manipulate the genome and create what we believe is a pretty interesting analog rodent analog of the human condition. We don't have genetic models in non-human primates, so we end up doing studies in non-human primates where we we we mimic exactly the surgical procedure by which we will access the inner ear, and then we end up either using a surrogate marker, GFP, or we end up detecting the human otoferln, in the non-human primate, which is quite hard.Laurence Reid: But we've sort of figured out how to do that now. And really what you're looking at is, is, is really is efficiency of the delivery and expression process. And then when you can't measure a fixing of the genetic burden and so at Decibel, we spend a lot of time using our genomics platform to really be able to define molecular control of our gene therapy. So we're really trying to express the transgene selectively in the cell types where nature intended it to function. So, you know, calcium sensor in the wrong in the wrong cell type one might fear, and we have data that suggests, that that may be a problem. So Decibel is really invested very significantly in sophisticated molecular control of our gene therapies. And so when we do the experimentation in the non-human primate we're looking at, are we getting good delivery throughout the cochlea? Are we getting good infectivity throughout the cochlea and then expression of basically a surrogate marker? Because we we can't change the physiology of a of a normal non-human primate. So it's really all about about surgery, delivery expression. And then obviously you then got a stable transgene expression, it turns out, rises over the over the weeks and months after after after the transduction. And so we're measuring that. And that's going to play ultimately into clinical trial design, both in terms of safety and an end points that will measure in human being. [musical interlude]Harry Glorikian: Let's pause the conversation for a minute to talk about one small but important thing you can do, to help keep the podcast going. And that's leave a rating and a review for the show on Apple Podcasts.All you have to do is open the Apple Podcasts app on your smartphone, search for The Harry Glorikian Show, and scroll down to the Ratings & Reviews section. Tap the stars to rate the show, and then tap the link that says Write a Review to leave your comments. It'll only take a minute, but you'll be doing a lot to help other listeners discover the show.And one more thing. If you like the interviews we do here on the show I know you'll like my new book, The Future You: How Artificial Intelligence Can Help You Get Healthier, Stress Less, and Live Longer.It's a friendly and accessible tour of all the ways today's information technologies are helping us diagnose diseases faster, treat them more precisely, and create personalized diet and exercise programs to prevent them in the first place.The book is now available in print and ebook formats. Just go to Amazon or Barnes & Noble and search for The Future You by Harry Glorikian.And now, back to the show.[musical interlude] Harry Glorikian: I would assume that some level of spatial genomics, the new technologies that are out there, must be hugely helpful to see the different cell types, where they are and what type they are. And you know is actually lighting up and changing versus what you don't want to light up and change. So yeah. So I had a great interview with Resolve on their system, which I think is going to be the next frontier, because what you're saying is, what cell type, where it is, and did I make the change in the exact one that I wanted?Laurence Reid: That's exactly right. So my my colleagues, long before I was here, invested in building a platform that we think is still, we have a database of over 3 million molecular profiles of the cells of the inner ear, which we think is a unique asset. And basically applying the tools of single cell genomics, which is the ability at the level of individual cells in the organ of an individual animal to analyze comprehensive gene expression. And so what we've been able to do, and I think this is part of just changing our attitude to how do we understand the cells of the inner ear and therefore how can we think about manipulating them pharmacologically to open up the field? And so we have a complete molecular characterization of, there are about 30 or so important cells in the inner ear and there's two or three subsets of those cells, starting with the cells that I talked about that are probably the critical therapeutic targets. And so we have a detailed molecular understanding of the composition of the level of gene expression of each of these different cell types. And we look at them a lot as they as they as they differentiate and form in a natural process, because we think that holds the answer ultimately to regenerating them as part of this next part of our strategy. But it's also taught us about how individual cells control gene expression. And I mean, otoferlin is expressed essentially in an adult animal only in the so-called inner hair cells. And that's what we then aim to replicate with our gene therapy. And so we've been able to take our genomics platform to define genetic regulatory elements that drive our trans genes in our gene therapies to express selectively in the most important cell type where you need it and not elsewhere. We know from our animal studies that that has a beneficial impact on on on the therapy and that the durability of the therapy. So that's our overall molecular goal, but it leverages this platform of single cell genomics.Harry Glorikian: So I've seen company presentations. Like you guys are, you know, you intend to initiate a phase one, clinical trial of of DB-OTO. I mean, how is that going? I mean, what are the big technical or medical barriers, where you're thinking about testing gene therapy? Like, I mean, you know, where are you guys in all that?Laurence Reid: Yeah. So so we what we've and I'm going to be precise as a public company, I need to be careful with my disclosures. So apologies in advance. But what we said is that we'll initiate will file an IND or a CTA in Europe this year and and move into our first in human study this year. And so we're in the you know, we're deep in all the almost classical, you know, pre-IND work of making material and, you know, and testing it in, in the final, you know, GMP tox studies and making material of a caliber that'll that'll go into human beings, which is very exciting. And that's, you know, that's that's what we're working on. Those are the two sort of basic barriers. I mean, we have published and talk publicly about a lot of our animal data, what I sort of recited a few minutes ago, small animals to large animals. I think we understand the basic pharmacology and now it's okay, scale up, make the material for human being, you know, GMP material for human beings, test the material, you know, in more prolonged formal toxicology studies, you know, and move it into human beings so that that work is ongoing. The other part that's really fascinating that you would appreciate is, you know, in a rare disease like this, a lot of very interesting discussions about about what's the exact patient cadre in which one starts a clinical trial.Laurence Reid: And we spend a lot of time building relationships with with clinicians, particularly in Europe, but also in the US, who really invested in understanding the genetic basis of of children in their region with genetic forms of auditory neuropathy. And we have a fantastic collaboration with our colleagues in Madrid at the Roman y Cajal, who have a database that is essentially all of the all of the known diagnoses of otoferlin deficiency in Spain. And so they've done so we have been able to help them do a lot of natural history work. What is what is the progression of the condition and how do we find these kids? And so we ultimately not necessarily immediately, but the ultimate goal is to treat children very early in life. These kids are now once they're diagnosed, they would get a cochlear implant really probably around the end of their first year of life. It used to be more like two, but that age has come down from a medical perspective. Being born profoundly deaf is the phrase is is a neurodevelopmental emergency. And I talked a lot about about old people. But for a kid, the the or a baby, the issue is that hearing lack of hearing impacts that their initial social interactions that their generation of language skills and their ability there and that and that feeds into their cognitive development.Laurence Reid: So there's a there's a whole set of emotional interactions that are happening very early in life. And of course, with so much cognitive development going on and the hearing is, is the absolute gate to a lot of that happening. And so it's widely, widely agreed that this phrase, a neurodevelopmental emergency, is what physicians use. So so ultimately, we need to be treating these kids in the first year or two of their life. And you know, how soon we'll get there remains to be seen. And it is an ongoing discussion. But that's that's where that's where ideally we would end up. While at the same time, as I said, we know we can intervene in animals later in their lives. So we're optimistic that we're going to be able to take adolescents and and children beyond the first year or two of life and still be able to have a positive impact on them. Well, that's the vision for sort of the broader applicability, not just in a newborn baby.Harry Glorikian: Yeah. I mean, you know, I mean, a child's, you know, the neuroplasticity or how easily that their brain or their system adapts and changes. I could see, you know, the drug having a much more profound effect in that population. I mean, in older people, I like to believe that we still have neuroplasticity, because I'm constantly evolving and changing. But, you know, I also sometimes think we're sort of stuck and maybe maybe don't have. But, you know, the human body is an amazing machine. But, you know, it brings me like one of the biggest themes on this show is like data, data, data and how that intersects biology. And, you know, what you're talking about is identifying the right sets of data, the right patients to have this work done on so that you can achieve a level of success. We all know that if you pick the wrong patients. Like you're utterly almost doomed for failure, or you're going to have an effect that you really didn't want to have. So how much of of Decibel's work or approach is is rooted in "Here's the data, here's the patient." How much are you guys using that to drive every decision that you're making?Laurence Reid: It's a it's a really great question, actually. And the answer is a lot. In fact, as I think about Decibel and where I think the team that my predecessor built, Steve Holtzman, who of course, you know, is really, really exceptional, is is effectively translation in its broadest sense. Right. I think what differentiates Decibel is an outstanding understanding of the biology of the inner ear and that we've invested in in turning that into a genomic molecular understanding of every cell type. But it's then, okay, who's my patient? What, their molecular profile. And how do I link that back, feed that back into my discovery process? What are my animal models look like and how am I looking forward, you know, into ultimately into a clinical trial? And with people suffering from from congenital hearing loss age, which we try and intervene, becomes a big variable, as you're suggesting. And so, you know, if you're in the pharmaceutical R&D, it's like, okay, that's translational medicine he's talking about. And and it is I just think we do it really well. And it's really the essence of the scientific core of Decibel is linking our molecular work in the cells of the inner ear to a fantastic understanding of the patients, their individual phenotypes and how we look to bridge that gap between preclinical research and the clinic. And the the the truth is, I mean, there are no approved therapies and there hasn't been a lot of work, as I said, up front.Laurence Reid: But but it's not like we're we're complete, we're not we're not going to be the first people either to do a gene therapy in the ear, nor to try and develop a therapy. But the translation has been really poor. And I think that our ability to understand the mechanistic pharmacology, preclinical and clinically and then be confident that that was going to work in a human being has been really poor. And obviously genetics from a simplistic perspective is a fantastic way to bridge that gap. Right. We know which gene we're trying to fix. And therefore, is the ear able to be fixed in a child of one two years old? And can we get the gene there safely and effectively and turn it on in the right place? Right. But those are problems that you can break down and solve and you can analyze them in smaller animals and larger animals. Whereas I think historically, the preclinical data, how do you validate it in a human being or do we really know those mechanisms are going to work in a human being? Well, the outcomes have shown us that we didn't have all the understandings of that. And I think you look back on it and the ability to translate has been has been weak. And that's why the genetics is is so appealing as a formative place to to start and try and build a pipeline of therapeutics, at least in our opinion.Harry Glorikian: Yeah. It's funny because we're always coming back to this genetic part of it. And I remember like somebody saying to me way back, No, it wasn't that long ago, relatively speaking, but why would you want to sequence anything? Right? And now it's like it's the cornerstone of everything we're doing. Yeah, but. But you guys have another drug, right?Laurence Reid: We do.Harry Glorikian: That prevents ototoxicity, right. Damage to the inner ear.Laurence Reid: Yep.Harry Glorikian: And it's that's one of the most common side effects of chemotherapeutic drugs like cisplatin. I mean, for those people that are listening, right, these little hairs, it's the same thing as like maybe the hair on your head.Laurence Reid: Please don't go there. It confuses people.Harry Glorikian: But essentially, you've got a drug that you're working on this in this space.Laurence Reid: Yes, we do. So firstly, how are you just upset because of our relative quantity of hair here. The hair cells in your hair are very different than the hair cells on top of your head or other parts of your body. Their role is to transducer signals on the inside of your cochlea into the brain. So but the cisplatin based chemotherapy is still very, very commonly used around around the world and is quite efficacious in certain types of tumors. It's widely used, for example, in testicular cancer, just one example. And it comes but it comes with a couple of of fairly severe toxicities, one of which is it kills the hair cells in your ear. And it also damages their interactions with the nervous system. And earlier in Decibel's life when we were sort of using our biological thinking before we. That's what I would say when we started as a biology company and we explored different molecular molecular modalities as the right way to treat it. And now we are significantly focused on gene therapy. As we've been talking about, this program was home grown and we're pretty excited about it despite our core investment in gene therapy now. And what we have is a proprietary formulation of a molecule of sodium sulfate, which is a natural metabolite, and it chemically inactivates cisplatin. And so we actually administer this by an injection into the middle ear and then the active ingredient leaches into the inner ear. And we administer that about 3 hours or so in advance of the Cisplatin IV, so that by the time the cisplatin gets to the ear, the inner ear is already bathed in sodium sulfate. And so and then you have a chemical reaction in situ inactivates the cisplatin.Laurence Reid: And you know, it's interesting because some people don't find that very sort of biotech sexy, but it's actually an incredibly elegant way to to to stop the side effects of a molecule that has multiple, multiple molecular forms of damage that are probably being imposed on different cell types. So solving that biologically or biochemically is a very hard, diverse problem, whereas solving it chemically in situ we think is is very powerful. The principle to give some credit was validated by a company called Fennec, but they have an IV administration and they are constantly fighting between achieving good things in. As you might imagine, preventing against that toxicity without inhibiting the efficacy of the drug. And it's correct. And that's that is a very and they hopefully eventually will get approval for a fairly narrow pediatric population because it's been very hard to sort of thread the needle of can I protect without inhibiting the efficacy? Now if you go directly to the organ where the damage is being done, local administration of a proprietary formulation, so it sits in the ear, it's there in advance. Essentially, none of it leaches out into the circulation. So we have, we believe, negligible risk of inhibiting in any way the cancer benefit of the circulating cisplatin. So we're achieving a local protection and we're looking where we will be reporting some human proof of concept data. We've said in the first half of this year. So pretty excited about that, actually.Harry Glorikian: Yeah. I mean, you know, I don't need sexy. I just need something to, like, work, right? I mean, sexy is nice, but, you know, if it's working, it's working sometimes, you know.Laurence Reid: Right. So, so not not to compare protection of hearing against protection from people who are going to die of cancer. But it's an interesting example of where hearing health or ear health gets neglected. So in the context, you know, cisplatin is used in many cases with what people refer to as an intent to cure and so people can get cured. Young men, I think the cure rate is something like 95%. So you're talking about a young man, maybe 20 years old. He's going to live for 100 years, right? Maybe more. Maybe more. And nowadays and so the the importance of protecting his hearing at that age. And there are female cancers as well. But his hearing at that age for his long term health is incredibly important. But it gets it gets, unsurprisingly, neglected because the focus is on is on the cancer, which is which is understandable. But but we think that there's a really important opportunity to, you know, to provide a better overall solution for for those people that's going to have an incredible impact later in their life as their hearing would be naturally degenerating anyway. And and I think because of the the understandable stress when you're going through chemotherapy, you know, worrying about the hearing decrement, is it's just not top of mind. And so we've got some awareness. We've got some work to do to increase awareness there and hoping that some of our animal data might replicate in human beings because we think this could be fairly effective and really hopefully get it into the minds of oncology physicians. Is the goal that you should be thinking about this. You're trying to cure this patient. You're trying to whether it's a woman with ovarian cancer in her fifties or a young man with testicular cancer, they're going to live for decades to come. And we think it's important that they're hearing health is protected and we can help you do that potentially in a very powerful, rather simple way, actually.Harry Glorikian: So. I'm going to assume and you can correct me if I'm wrong, that if this gets through sooner than the gene therapy and can generate some revenue in the short term, you can then utilize that revenue to continue to fund the gene therapy programs.Laurence Reid: We're all always looking for money to do this, right, Harry?Harry Glorikian: So, unfortunately, that's the business we're in.Laurence Reid: That's the nature of the beast. Certainly, after we have our data in hand on the proof of concept, we'll be looking for an FDA interaction to define the path to registration, which we think could be relatively efficient. We have, you know, the medicine that effectively becomes an oncology supportive care medicine. It needs to be administered probably in the chemotherapy suite right in advance of a patient receiving their chemotherapy. So it needs to be marketed to an oncologist with a lot of education in the audiology community so that they're leaning on their oncology colleagues to you need to do this and you need to think about this as you're putting your patient through through chemotherapy. Ultimately, I think that that marketing to the oncologists, I don't think that's what's going to do that in itself. We're going to eventually bring a partner partner in to do that who is a specialist in marketing to the oncology community. And we want to be involved in rethinking about making sure that the ideological education and understanding is transferred into the cancer into the cancer world. And so that's that's a commercial strategy and structure that will will put together, you know, potentially starting when the data is in hand, but certainly some time between now and approval of the drug.Harry Glorikian: Well, Laurence, you know, I can only wish you the greatest success because and working in older people would be great, because I'm sure that I'm going to need this at some point, and some of my friends may also need it. But it was great to catch up with you. Great to talk. You know, I hope, you know, it's not as many years past again before we we get a chance to connect. So great to have you on the show.Laurence Reid: Thanks, Harry. I really appreciate it. And hopefully I've been able to provide some of the color and why we're so excited and think we're opening up a new area of therapy here for people with hearing loss and balance disorders beyond that. So really appreciate the opportunity. Thanks very much and great to see you.Harry Glorikian: Thank you.Harry Glorikian: That's it for this week's episode. You can find a full transcript of this episode as well as the full archive of episodes of The Harry Glorikian Show and MoneyBall Medicine at our website. Just go to glorikian.com and click on the tab Podcasts.I'd like to thank our listeners for boosting The Harry Glorikian Show into the top three percent of global podcasts.If you want to be sure to get every new episode of the show automatically, be sure to open Apple Podcasts or your favorite podcast player and hit follow or subscribe. Don't forget to leave us a rating and review on Apple Podcasts. And we always love to hear from listeners on Twitter, where you can find me at hglorikian.Thanks for listening, stay healthy, and be sure to tune in two weeks from now for our next interview.

Harry Glorikian has been a healthcare entrepreneur, author, podcaster, and company leader for the last 25 years. He has been at the intersection of the fast-moving science and business of healthcare and biotechnology. His latest book is 'The Future You: How Artificial Intelligence Can Help You Get Healthier, Stress Less, and Live Longer (https://amzn.to/3wCSVwn)'. In this episode, we discuss some of the amazing biothech breakthroughs over the past few years while sharing stories about how each of us has been using technology to improve both our health and productivity. This epoisode is brought to you by: * Riverside.fm (http://riverside.fm) - Use Coupon Code BEYOND for $10 off any subscription * CircleDNA (http://CircleDNA.com) - Use code ERIK for 33% OFF any CircleDNA kit

3 - 25 - 22 LIVE LONGER WITH THREE WHATS PER DAY by Maine's Coast 93.1

How to get inner and outer success and live longer with the creator of The VEEP Nutrition System Joel Greene He had his 10,000 hours already in before your guru ever began.    In the 1970's he was interval training  ​ In 1979 he was doing olympic lifts 3 hours every night. ​ In the 80's he began studying MCT's. ​ In 1990 he began studying the Keto diet. ​ In the early 90's he was doing what would be called intermittent fasting today. ​ In the mid 90's he experienced the rebound from chronic starvation. You read this today for this reason. ​ In the late 90's he went through his clean eating phase, his macro phase, his ancestral diet phase. ​ By 2001 he had his first nutrition website publishing the cutting edge research.  ​ By 2006 he came to the end of all the above and discovered none of it worked over time under real life pressure.  ​ In 2007 he authored the first article to the health and fitness community based on the new science linking gut bacteria and obesity. ​ in 2008 his website lookcut.com hit #2 in google for weight loss, with over 1,000 original groundbreaking articles that today represent many of the most widely copied ideas in nutrition. ​ In 2009 he launched  the worlds first diet system based on targeting the gut bacteria. ​ In  2010 he was implementing signal activation of the AMPK pathway. The gurus only began speaking to AMPK in 2017. ​ By 2013 he had the worlds largest body of anecdotal outcomes for body composition targeting the gut bacteria.  ​ In 2013 he published the first article to the health and fitness community on the dangers of MCT oil supplementation.   ​ Today, at 53, on 1 workout a week, eating whatever, whenever, with no drugs, sarms, prohormones, or ergogenic aids ever, he is the world leader in hacking the body. He is the real deal. He has done it longer and always been far ahead. He looks it, he lives it. What the guru's say is impossible he was living every day before they were guru's.   He has hacked peak human...   working out once per week,    eating whatever, whenever,   and does it all on fast food!    He is the future of real world health and nutrition, today.   ​ As creator of the VEEP Nutrition System, the worlds first commercially available program based on targeting gut communities to effect biomarkers, Joel also is a featured author, speaker, and guest in top tier publications like Muscle and Fitness, 24 Hour Fitness Digital Magazine, CBS Online, Superhuman Radio. His system has also been featured on the Dr. Phil Show where it has delivered astounding life changing results. 

In this episode, you'll learn why developing a strong aerobic system improves longevity, and I will provide you with simple methods you can implement into your exercise routine.   Try Primally Pure's amazing deodorant and their all organically sourced skincare products.   Use the code BLUEPRINT to get 10% off your order.   Paper 1: Interaction among Skeletal Muscle Metabolic Energy Systems during Intense Exercise Adaptation to Endurance and Strength Training   Paper 2:High-Intensity interval training for health benefits and care of cardiac diseases - the key to an efficient exercise protocol   _______________   ABOUT THE BLUEPRINT PODCAST:   Dr. Erik Korem's podcast, The BluePrint, is for busy professionals and Household CEOs who care deeply about their family, career, and health. Dr. Korem distills cutting edge-science, leadership, and lifeskills into simple tactics optimized for your busy lifestyle and goals.   Dr. Korem interviews scientists, coaches, elite athletes, entrepreneurs, entertainers, and exceptional people to discuss science and practical skills you can implement in your life to become the most healthy, resilient, impactful version of yourself.    ​​On a mission to equip people to pursue audacious goals, thrive in uncertainty, and live a healthy and fulfilled life, Dr. Erik Korem is a High Performance pioneer. He introduced sports science and athlete tracking technologies to collegiate and professional (NFL) football over a decade ago, and has worked with the National Football League, Power-5 NCAA programs, gold-medal Olympians, Nike, and the United States Department of Defense.   Erik is an expert in sleep and stress resilience, and he is the Founder and CEO of AIM7, a wellness app that provides custom exercise recommendations to improve the outcomes of programs and workouts you already love. It unlocks existing data from wearables and other apps to provide empathetic and scientific guidance that's perfectly in tune with your mind and body. _______________   SUPPORT & CONNECT:   Instagram - https://www.instagram.com/erikkorem/ Twitter - https://twitter.com/ErikKorem LinkedIn - https://www.linkedin.com/in/erik-korem-phd-19991734/ Facebook - https://www.facebook.com/erikkorem Website - https://www.erikkorem.com/ Newsletter - https://erikkoremhpcoach.activehosted.com/f/1 _______________   QUOTES:   “The key is using stress and being able to adapt to it and improve. That's what high performance is to me, the ability to adapt rapidly so you can achieve your potential. There are five key pillars to creating the conditions for adaptability: sleep, exercise, mental resilience, nutrition, and community/relationships.” Dr Erik Korem   “I maybe have a different concept on leadership. To me, leading is a verb. If you're leading, you're a leader. If you're swimming you're a swimmer, if you're driving you're a driver. If you're leading you're by definition a leader. I define leading as being looked to in a particular moment to make a decision or perform an action based on your unique gifts and abilities. So by that definition, everybody is a leader. All rank and role really describe is how many people are hoping you get it right when it's your turn to wear the weight.” - Clint Bruce   John Danaher on high performance mindset and resilience:  “Whenever you are sparring, your mind will have a given direction of focus. The most basic division is between self focus and focus on the opponent.” - John Danaher on high performance mindset and resilience   Blue Print host Dr. Erik Korem on high performance mindset and resilience:  “In sport, our goal is to develop the most adaptable athletes with the most resilience who can consistently obtain their high performance mindset and potential.” - Dr. Erik Korem on high performance mindset and resilience, host of The Blue Print   John Danaher on high performance mindset and resilience:  “Philosophy was crucial because it is among the best means of developing a problem solving mindset.” - John Danaher on high performance mindset and resilience   Blue Print host Dr. Erik Korem on high performance, performance mindset, and resilience:  “The key is using that stress and being able to adapt to it to improve. That's what high performance to me is: the ability to adapt rapidly so you can achieve your potential.”  - Dr. Erik Korem on high performance, performance mindset, and resilience, host of The Blue Print   John Danaher on high performance mindset and resilience:  “The greatest determinant of the outcome of your matches over time by a landslide is your training and lifestyle mentality. This is the high performance mindset you carry every day as you train and progress.” - John Danaher on high performance mindset and resilience _______________ Hot Pie Media is an on-demand digital audio/video entertainment network with interests primarily in the creation of original, relevant and entertaining podcasts. See omnystudio.com/listener for privacy information.

On Cool Science Radio for March 24, 2022, Lynn and John's guests are: (01:42) Nims Purja- the first man ever to summit all 14 of the world's 8000-meter “Death Zone” peaks, and he did it in less than 6 months. He also authored a book about his experience; Beyond Possible: One Soldier, Fourteen Peaks- My Life in the Death Zone. If you are familiar with Netflix's “14 Peaks” you will not want to miss this conversation. (24:46) Harry Glorikian then joins the show. He has just written The Future You: How Artificial Intelligence Can Help You Get Healthier, Stress Less, and Live Longer.

Kara Fitzgerald, ND, IFMCP is a naturopathic doctor and a leading voice in the intersection of nutrition, epigenetics, and aging. She is the author of the new book Younger You: Reduce Your Bio Age and Live Longer, Better and she was the first-ever recipient of the 2018 Emerging Leadership Award from the Personalized Lifestyle Medicine Institute in recognition of her work on DNA methylation. Receiving her doctorate from the National University of Natural Medicine, she is on the faculty at the Institute for Functional Medicine (IFM) and is an IFM Certified Practitioner with a clinical practice in Newtown, Connecticut.   In this episode, we talk about biological aging versus conventional aging, how it relates to women's health, Kara's unique journey to motherhood at age 50, why we should be focusing on healthspan instead of lifespan, and so much more! To learn more visit https://nicolejardim.com/podcasts/causes-of-biological-aging-and-the-connection-to-womens-health-dr-kara-fitzgerald/. Podcast Production Support: Amazing Gains | https://listenerstoclients.com