The James Altucher Show

James Altucher

James Altucher interviews the world's leading peak performers in every area of life. But instead of giving you the typical success story, James digs deeper to find the "Choose Yourself" story - these are the moments we relate to... when someone rises up from personal struggle to reinvent themselves. The James Altucher Show brings you into the lives of peak-performers: billionaires, best-selling authors, rappers, astronauts, athletes, comedians, actors, and the world champions in every field, all who forged their own paths, found financial freedom and harnessed the power to create more meaningful and fulfilling lives.

  1. 13 hr ago

    Kareem Abdul-Jabbar: Becoming Kareem, the Skyhook, and the Search for a Self [From the Archive]

    Episode Description: Kareem Abdul-Jabbar joins James for a From the Archive conversation about basketball, identity, mentorship, faith, writing, civil rights, and his book Becoming Kareem: Growing Up On and Off the Court. The episode begins with basketball. James asks Kareem how the game has changed since his playing days, and Kareem explains the shift toward the three-point shot, the rule changes around physical defense, and the way modern spacing has altered how teams score. But the conversation quickly becomes deeper than basketball. James sees Becoming Kareem as a book about the search for identity. Kareem agrees, explaining that Black Americans have often had identities imposed on them—first through slavery, then through Jim Crow, then through the lingering assumptions and limitations of American racism. His own journey required rejecting those imposed definitions and building an identity he could be proud of. Kareem emphasizes the importance of mentors. Some were direct mentors, like John Wooden and Bruce Lee. Others were cultural or intellectual mentors, like Malcolm X. Together, they helped him understand not only how to succeed, but how to think about who he wanted to become. The central advice Kareem gives young people is simple: knowledge is power. Learn what your future could be. Seek out what motivates you. Do not let someone else define your path. Every person has a unique spark, and the work is to discover where that spark leads. James and Kareem also talk about fundamentals. Kareem remembers John Wooden expecting him to graduate and teaching his players the smallest details of preparation, including how to put on their socks. The lesson is that success depends on doing the basic things correctly before the glamorous work begins. The conversation then turns to Kareem’s life as a writer. James asks about the challenge of moving from basketball into Sherlock Holmes fiction. Kareem explains that writing Mycroft Holmes required serious preparation: understanding Victorian England, Arthur Conan Doyle’s canon, and the possibilities hidden inside Mycroft’s brief appearances. Kareem also reflects on Islam, his conversion, and the way faith gave him a moral anchor. He talks about being raised Catholic, studying Islam, reading The Autobiography of Malcolm X, and finding a belief system that helped him understand right and wrong. Near the end, James asks about Kareem’s seriousness in photos and the HBO documentary Kareem: Minority of One. Kareem explains that his height made him visible everywhere he went, and that constant scrutiny made him more guarded than someone who could disappear into a crowd. The episode closes with the idea that everyone is, in some way, a minority of one. Every person has to figure out their own path, and often that path is not the one their parents followed. Kareem’s story is about basketball, but it is also about becoming a whole person. Editorial Note: This is a From the Archive episode. References to Kareem’s career scoring record, the state of the NBA, Becoming Kareem, and his then-current writing projects reflect the original recording period. Since this conversation was recorded, LeBron James has surpassed Kareem Abdul-Jabbar as the NBA’s all-time leading scorer. The conversation remains historically valuable because it captures Kareem reflecting on his record, his era, and his evolution before that milestone changed. What You’ll Learn: How Kareem thinks basketball changed after his era.Why the three-point shot transformed modern NBA strategy.Why Becoming Kareem is ultimately a book about identity.How imposed identity shaped Kareem’s experience as a Black American.Why knowledge is power in the search for a future.How mentors helped Kareem understand who he was and who he wanted to become.What John Wooden taught him about education, discipline, and preparation.Why fundamentals matter before talent can fully express itself.How the lesson of “putting on your socks” applies far beyond basketball.Why Bruce Lee’s “one kick 10,000 times” idea connects to the skyhook.How Kareem approached writing Sherlock Holmes fiction through Mycroft.Why religion became part of Kareem’s search for identity.How Islam gave him a moral anchor.Why constant public scrutiny made him more guarded.Why competitive fire separates great athletes from talented ones who do not fully develop.Why every generation has to find its own path. Timestamped Chapters: [02:38] How Basketball Changed Kareem explains how the three-point shot, rule changes, and less physical defense changed the modern NBA. [04:14] Beyond Basketball James introduces Becoming Kareem and frames Kareem’s life as a continuing search for identity. [05:44] Rejecting an Imposed Identity Kareem explains how Black Americans have had identities imposed on them and why his journey required building one he could be proud of. [07:03] Mentors and the Making of a Self James points to Coach Wooden, Bruce Lee, Muhammad Ali, Wilt Chamberlain, Malcolm X, and other influences who shaped Kareem’s identity. [08:17] Knowledge Is Power Kareem says young people should seek knowledge, understand what motivates them, and choose a path instead of accepting one imposed by others. [09:57] Education, UCLA, and Community Kareem explains why earning a college degree mattered to him personally and to his community. [11:12] Finding Your Path in America Kareem talks about the many ways to become successful and the need to figure out what you want to pursue. [12:12] Fundamental Preparation Kareem explains why every field requires fundamentals, whether basketball, chemistry, law, or any other discipline. [13:05] John Wooden and the Socks Lesson James and Kareem discuss Wooden teaching players how to put on socks and why small details determine whether bigger work can happen. [14:26] The Skyhook and 10,000 Kicks James connects Bruce Lee’s practice philosophy to Kareem’s skyhook and the discipline of repeating one skill until it becomes mastery. [15:46] Becoming a Sherlock Holmes Writer Kareem explains the challenge of entering a new creative field and writing about Mycroft Holmes. [17:02] Finding the Blank Space in Mycroft James notes that Kareem built a story from Arthur Conan Doyle’s brief suggestion that Mycroft was, at times, the British government. [17:39] Religion and Identity Kareem explains how his Catholic upbringing, interest in monotheism, African history, and The Autobiography of Malcolm X led him toward Islam. [18:49] A Moral Anchor Kareem says Islam helped him clarify his belief system and understand right and wrong. [20:06] A Minority of One James asks why Kareem often appeared so serious in photos, and Kareem explains the effect of lifelong scrutiny. [21:31] What Coach Wooden Still Teaches Him Kareem reflects on Wooden’s example, expectations, and belief that effort in academics and athletics was worthwhile. [22:47] Talent, Skill, and Competitive Fire Kareem says competitive fire often separates championship athletes from talented players who never fully make it. [24:35] Civil Rights and Speaking Up Young James asks about the Cleveland Summit, Muhammad Ali, and Kareem’s early role in civil-rights conversations. [25:54] Everyone Is a Minority of One James and Kareem return to the question of identity and the need for each generation to define its own path. Additional Resources: Kareem Abdul-Jabbar Official WebsiteBecoming Kareem — Hachette Book GroupMycroft Holmes Series — Penguin Random HouseKareem Abdul-Jabbar — Simon & Schuster Author PageWe All Want to Change the World — Penguin Random HouseGame of Death — Janus FilmsSee Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

  2. 23 Aug

    Seth Godin: The Smallest Viable Audience and the Work That Might Not Work [From the Archive]

    Episode Description: This is a From the Archive episode with Seth Godin. Seth Godin returns to the show for a conversation about making work that matters in a world obsessed with hits, rankings, followers, algorithms, and approval. James opens by talking about Seth’s long body of work: Purple Cow, Linchpin, Graceful, thousands of blog posts, and Seth’s then-new podcast Akimbo. Seth explains why he had thought about podcasting for years but resisted it because audio creates a different kind of intimacy. In print, the voice in the reader’s head is the reader’s own voice. In audio, the voice belongs to the person speaking. That intimacy made podcasting powerful, but also something Seth wanted to handle carefully. From there, James asks about the structure of Akimbo. Seth says the key to a strong solo format is assertion. What are you saying that is not obvious? What are you asking people to see differently? If you cannot make the point in 15 minutes, maybe you cannot make it at all. The conversation then moves into hits. Seth explains that platforms benefit from the long tail, but creators can suffer inside it. Amazon, iTunes, Facebook, Twitter, and other platforms need endless creators to show up with work, but they also train people to believe that if they do not hit number one, they failed. Seth’s alternative is the smallest viable audience. Find the specific group you seek to serve. If it is 500 people, make something so good for those 500 people that they cannot help but tell someone else. That is more useful than chasing a vague mass audience or gaming a category so you can call yourself a bestseller. James and Seth connect this to Purple Cow. The book spread because Seth gave people a phrase they could use in a meeting. A “purple cow” became a way to describe something remarkable before people necessarily knew where the phrase came from. That is a key idea in the episode: every hit changes the people it touches. It does not simply entertain. It gives people a new belief, a new language, or a new way to see. Seth also explains the deeper forces under a lot of culture: fear and status. Fear keeps people from doing work that might not work. Status makes people compare themselves to the wrong people and measure the wrong things. The creator’s job is to notice both, then act generously anyway. The episode closes with the craft itself. Seth says he does not check blog stats, does not read Amazon reviews, and does not shape his work around critics. The question is simpler: Did you change someone for the better in a way you are proud of? If yes, do it again. Editorial Note: This is a From the Archive episode. References to Akimbo as a newer podcast, This Is Marketing as an upcoming book, the altMBA, platform dynamics, bestseller lists, podcasting, and Seth’s then-current projects reflect the original recording period. What You’ll Learn: Why Seth Godin resisted podcasting for years.How audio creates a different kind of intimacy than writing.Why a solo podcast needs a clear assertion.Why Seth focuses on overlooked, underthought, ignored, or uncomfortable ideas.Why platforms benefit from the long tail more than most creators do.Why chasing hits can distort the work.What Seth means by the “smallest viable audience.”Why a hit has to change people, not just entertain them.How Purple Cow spread by giving people useful language.Why trying to avoid criticism often makes work invisible.How fear and status shape culture, creativity, marketing, and self-worth.Why random events should not be taken personally.Why generosity requires emotional labor.What it means to choose your customers and choose your future.Why second-order teaching matters more to Seth than personal credit.Why being “amazing” starts long before the hustle.Why the best work lives in the territory of “this might not work.”Why Seth does not read reviews or track stats.How to protect the craft from outside measurement. Timestamped Chapters: [03:19] Seth Godin Returns James welcomes Seth back and introduces his books, blog, and new podcast Akimbo. [05:15] Why Seth Started a Podcast Seth explains that he had thought about podcasting for years, but worried about the intimacy of audio. [07:05] Choosing the Right Medium Seth explains why a podcast reaches people differently than writing and why he avoids formats, like Twitter, that do not fit the work he wants to do. [08:17] The Solo Podcast Format James asks about Seth being the only guest on Akimbo, and Seth says a solo show needs a strong assertion. [09:24] Overlooked, Underthought, and Hard to Confront Seth distinguishes his style from pure contrarianism and says he is drawn to things people have missed or avoided. [10:47] Hitsville and the Long Tail James brings up Seth’s Akimbo episode on hits, platforms, Amazon, podcasts, and the explosion of available work. [12:21] The Trap of Platform Thinking Seth explains how platforms train creators to feel defective if they do not become number one. [13:25] Editors Cannot Pick the Hits Seth argues that people cannot reliably predict hits and that creators should not try to game their way to the top. [15:00] The Smallest Viable Audience Seth explains why serving a specific small group can be more powerful than chasing the masses. [16:21] This Might Not Work James brings up Seth’s large limited-edition book and how it was built for a specific audience instead of the broad market. [17:26] Why You Cannot Reverse-Engineer Gangnam Style Seth explains why many talented people try hard and still do not hit, because hits also involve randomness. [19:14] Don’t Bet Your Work on Oprah or Bieber Seth explains why waiting for a powerful person to anoint your work is a bad strategy. [20:13] Finding the People Who Must Share It Seth uses the idea of R naught to explain why a small group of people who must tell others can create spread. [20:35] Why Purple Cow Spread Seth explains how the milk carton, the title, and the phrase itself helped people talk about the idea. [22:26] Every Hit Makes a Change Happen Seth says the real question is: What change are you trying to make in the people who engage with your work? [23:35] What Akimbo Is Trying to Change Seth explains that Akimbo is for people who want to think more deeply about culture and change it for the better. [25:14] Randomness, Fear, and Status James connects Seth’s episodes, and Seth explains that much of his work is about fear and status. [27:13] Don’t Take Randomness Personally Seth says creators should expect that many launches will not become hits and organize their work accordingly. [28:33] The Craft vs. the Outside World James and Seth discuss how publishers, reviewers, bestseller lists, rankings, and critics can distract from the actual work. [29:21] It’s Not for You Seth explains why broadening a project for everyone can make it average, and why creators should be willing to say who the work is for. [32:29] What Will You Do With the Microphone? Seth says he wakes up thinking about the people he seeks to serve, not how to increase traffic or revenue. [33:30] Why Seth Ignores Stats and Reviews Seth explains that he does not check blog traffic, book sales, or Amazon reviews because that helps him keep doing the work. [34:43] Choose Your Customers, Choose Your Future Seth gives the six-word version of audience selection and explains why customers shape the work. [35:04] Thirsty, Dissatisfied, and Generous Seth describes his ideal audience and explains generosity as emotional labor in service of other people. [37:22] Second-Order Teaching Seth says he wants to be judged not by his work, but by what people who learned from him teach others. [38:18] Be the Person They Want to Find Seth explains why the real work happens before SEO, LinkedIn tactics, or hustle. [40:02] How Do You Become Amazing? James asks the direct question, and Seth says the essence is confronting fear and doing emotional labor. [41:00] Where Art and Innovation Live Seth says the work that might not work is where generosity, art, innovation, and magic happen. [42:05] Warby Parker and the Risk of Something New Seth uses Warby Parker as an example of doing something advisors said would not work. [42:49] How Seth Builds an Episode Seth explains how a coincidence becomes a podcast: collect stories, find the non-obvious insight, and connect the dots. [45:07] Seth the Collector Seth describes himself as someone who collects moments, stories, and observations that may become blog posts or lessons. [46:34] Self-Awareness and the Craft James connects Seth’s work to the ability to keep distance between your belief in the craft and society’s measurements. [47:04] Jiro, Awards, and the Wrong Reward Seth talks about Jiro Dreams of Sushi and the danger of external validation taking over the craft. [48:40] Marriage, Space, and Stories James asks Seth about marriage, and Seth talks about listening, keeping promises, creating space, and the stories people tell themselves. [52:18] Advice for James’s Podcast James asks how to change the show, and Seth suggests making one out of every four episodes a solo episode. [53:08] This Is Marketing and Closing Thoughts Seth says his next book is This Is Marketing, James recommends Akimbo, and Seth signs off by telling him to keep making a ruckus. Additional Resources: Seth Godin Official WebsiteSeth’s BlogAkimboAkimbo on Apple PodcastsThis Is Marketing — Penguin Random HousePurple Cow — Seth’s StorePurple Cow — Penguin Random HouseLinchpin — Penguin Random HouseThe Dip — Penguin Random HouseThe Practice — Penguin Random HouseBy the Way Bakery See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

  3. 22 Aug

    Arianna Huffington: The Sleep Revolution, Microsteps, and the Joy of Being Awake [From the Archive]

    Episode Description: This is a From the Archive episode with Arianna Huffington. Arianna Huffington returns to the show for a conversation about sleep, success, reinvention, and the cultural delusion that burnout is the price of achievement. James begins by asking practical sleep questions: Is nine hours too much? Can sleep be split into two four-hour blocks? Arianna explains that for most people, seven to nine hours is the real range, and that sleep should leave a person fully recharged, not limping through the day waiting for a second shift of rest. From there, James rewinds to Arianna’s career. Before The Huffington Post, before Thrive Global, before The Sleep Revolution, Arianna had already spent decades writing, appearing on television, entering politics, changing positions, and reinventing herself. She credits her mother with giving her the belief that failure was not the opposite of success, but a stepping stone toward it. One of the central stories is Arianna’s second book being rejected by 36 publishers. Out of money and unsure whether she should remain a writer, she walked into a bank in London and asked for a loan. The manager gave it to her. That small act kept her on the path. James and Arianna then talk about The Huffington Post: its rough launch, brutal early reviews, the team behind it, the importance of creating a platform, and the thrill of giving unknown people a chance to be heard. Arianna tells one of her favorite stories about a homeless teenager whose writing on HuffPost helped lead to Harvard discovering him. The conversation then turns to the 2007 collapse that changed Arianna’s relationship with sleep. Arianna says the problem was not just personal overwork. It was a collective belief that sleep deprivation is required for success. But James pushes her on the personal side too, and Arianna acknowledges perfectionism: building a company, raising daughters, trying to be a perfect mother, and working through the night after college-tour days with her daughter. Arianna’s answer is not a rigid sleep doctrine. It is a series of small steps. Build a transition. Remove devices from the bedroom. Lower the lights. Take a bath or shower. Read a physical book. Use gratitude as the closing scene of the day. If you wake up at 3 a.m., meditate instead of spiraling. The episode closes with joy. For Arianna, sleep is not only about health and productivity. It is about being present enough to experience life while it is happening. Editorial Note: This is a From the Archive episode. References to Arianna’s role at The Huffington Post, HuffPost’s size and global expansion, her contract, sleep resources, and digital products reflect the original recording period. This episode discusses sleep, medication, insomnia, health, and wellbeing. It should not be treated as medical advice. Anyone dealing with chronic insomnia, sleep medication dependence, depression, narcolepsy, or other health concerns should speak with a qualified clinician. What You’ll Learn: Why Arianna says sleep deprivation is not a requirement for achievement.How her 2007 collapse changed her view of success, productivity, and wellbeing.Why most people need seven to nine hours of sleep.Why she sees failure as a stepping stone, not the opposite of success.How her mother shaped her courage, optimism, and relationship to fear.Why The Huffington Post was built as both a journalistic enterprise and a platform for voices.How brutal early reviews tested the HuffPost team.Why Arianna believes teams matter most during hard times.How perfectionism contributed to her burnout.Why sleep affects health, productivity, decision-making, creativity, and joy.Why dreams matter for memory, insight, and new ideas.How to start a sleep transition with small microsteps.Why removing devices from the bedroom is one of the first practical changes.How gratitude can become the “closing scene” of the day.Why waking up in the middle of the night is not the problem—the stress spiral is.How meditation can help turn middle-of-the-night waking into rest.Why being exhausted makes people miss the moment. Timestamped Chapters: [03:02] Arianna Huffington ReturnsJames introduces Arianna and The Sleep Revolution, and they start with the practical question of how much sleep is enough. [03:51] Can You Split Sleep Into Two Blocks?James asks about sleeping four hours in the afternoon and four at night; Arianna explains why waking up fully recharged matters. [05:16] The Secret Origins of Arianna HuffingtonJames moves from sleep to Arianna’s long career of writing, media, politics, public life, and reinvention. [06:20] Failure as a Stepping StoneArianna credits her mother with teaching her to aim high and see failure as part of the path. [08:06] Rejected by 36 PublishersArianna remembers running out of money in London, walking into Barclays Bank, and receiving the loan that helped her stay a writer. [09:52] The Huffington Post BeginsArianna explains HuffPost as both a journalism operation and a platform for known and unknown voices. [11:28] The Magic of the InternetArianna tells the story of a homeless teenager whose HuffPost piece helped bring him to Harvard’s attention. [11:48] When the Launch Reviews Were BrutalJames asks whether Arianna ever worried HuffPost would fail, and she remembers harsh early criticism. [12:42] Everything Is Rigged in Your FavorArianna describes the spiritual belief that helped her move through fear, uncertainty, and dark periods. [13:18] Moving Continents After HeartbreakArianna explains how leaving a relationship in London led to her life in America, her daughters, her career, and The Huffington Post. [14:19] Life After Selling HuffPostJames asks how Arianna’s life changed after the sale, and she explains why the company still felt new because it kept evolving. [15:20] The Collapse That Changed EverythingArianna connects her 2007 collapse from exhaustion to the wellness work that eventually became The Sleep Revolution. [16:32] The Collective Delusion About SleepArianna explains why modern culture wrongly treats sleep deprivation as essential to achievement. [18:02] Perfectionism, Work, and MotherhoodJames pushes on the personal side of Arianna’s burnout, and she identifies the pressure to be perfect at work and at home. [20:16] Why Sleep MattersArianna lays out the benefits of sleep across health, productivity, decision-making, creativity, and emotional life. [21:53] What the Brain Does While We SleepArianna explains why sleep is not passive downtime, but a period of active cleanup and restoration. [23:21] Sleep and ProductivityArianna argues that sacrificing sleep for work backfires because it reduces judgment, creativity, engagement, and performance. [25:08] Sleep as a Performance EnhancerJames brings up willpower and negotiation, and Arianna adds the example of athletes using sleep to improve performance. [26:49] First Understand the CrisisArianna explains why people need to change their minds about sleep before they can change their habits. [27:30] Dreams, Memory, and InsightArianna talks about dreams and recommends writing them down when you wake up. [28:32] Sleeping Pills and Better AlternativesJames asks about medication, and Arianna points to behavioral approaches and sleep preparation. [29:50] The Sleep TransitionArianna explains the importance of beginning somewhere, even with just five or ten minutes. [30:57] Escort Your Devices Out of the BedroomArianna recommends turning off phones, laptops, and tablets before bed and creating a clean boundary between day and sleep. [31:24] Bath, Books, Temperature, and GratitudeArianna describes her wind-down routine: water, dedicated sleep clothes, lower lights, a cool room, physical books, and three things she is grateful for. [33:42] The 3 A.M. Anxiety SpiralJames shares his method for postponing middle-of-the-night anxieties until the afternoon. [34:14] Meditation in the Middle of the NightArianna says waking up is not the problem and explains why meditation helps her return to sleep. [36:28] Sleep, Wellbeing, and JoyJames asks whether Arianna feels happy, and she says sleep helps her bring more joy into everything she does. [37:49] Don’t Miss the MomentArianna defines joy as being fully engaged and grateful, and shares her mother’s reminder that this moment is all we have. Additional Resources: Arianna Huffington Official WebsiteThe Sleep Revolution — Penguin Random HouseThrive — Arianna HuffingtonThrive Global — Arianna HuffingtonArianna Huffington’s TED Talk: “How to succeed? Get more sleep”Pulitzer Prize: David Wood of The Huffington PostThe Female Woman — Google Books See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

  4. 14 Aug

    Mike Massimino: Why Failure Couldn't Keep this Astronaut from Outer Space [From the Archive]

    Episode Description: Mike Massimino’s path to space was not a straight line. It was a long series of obstacles, failures, second attempts, and decisions not to quit. In this From the Archive conversation, James talks with Mike about his memoir Spaceman, his two shuttle missions to service the Hubble Space Telescope, his career at NASA, his work at Columbia, and the deeper lessons behind becoming an astronaut. Mike explains that spaceflight may look impossibly complex from the outside, but NASA makes it possible through preparation, checklists, training, repetition, and teamwork. In space, even the hardest work has structure. Back on Earth, ordinary life can sometimes feel harder because there is no checklist for getting through the day. James and Mike talk about the view of Earth from orbit and why Mike’s first reaction after a spacewalk was: “The Earth is a planet.” From space, Earth no longer looks like a safe, permanent background. It looks like a fragile home traveling through a dangerous universe. The conversation then moves back to Mike’s childhood. He watched Neil Armstrong walk on the moon and saw the New York Mets win the World Series in 1969, but he did not believe becoming an astronaut was realistic. Astronauts seemed like superheroes. It felt like something other people did. Still, the dream stayed with him. Mike describes failing his PhD qualifying exam at MIT, being told he might not be suited for the program, and deciding to try again anyway. He talks about applying to NASA four times, being rejected, failing the medical exam because of his eyesight, and then doing the seemingly impossible: training his eyes to pass the standard without surgery. For James, this becomes the central lesson. Most people would have accepted medical disqualification as proof that the dream was over. Mike saw it as another obstacle. The episode also explores what “the right stuff” really means. Mike pushes back against the old image of the astronaut as a lone, fearless test pilot. The real right stuff, he says, is whether someone can be trusted with your life. Can they work on a team? Will they help when you need help? Will they ask for help when they need it? Near the end, James identifies another pattern in Mike’s life: he may not have been the best at any single thing, but he became unusually good at a combination of things. Astronaut. Engineer. Spacewalker. Teacher. Communicator. Author. Public face for science. That combination made him uniquely valuable. The result is a conversation about space, but also about persistence, meaning, teamwork, and the improbable path from childhood dream to real achievement. Editorial Note: This is a From the Archive episode. References to NASA programs, the Space Launch System, Orion, Commercial Crew, SpaceX, Boeing, Blue Origin, Virgin Galactic, the shuttle program, and Mike’s recent book activity reflect the original recording period. What You’ll Learn: Why astronauts rely so heavily on checklists, procedures, training, and team support.How the view of Earth from space changed Mike Massimino’s relationship to the planet.Why Mike believes life likely exists somewhere else in the universe.What the Hubble Deep Field revealed about galaxies hiding in a seemingly empty patch of sky.Why childhood dreams can matter even when they seem impossible.How Mike decided which dreams were worth paying the price to pursue.Why failing at MIT did not end his path to NASA.How he handled repeated NASA rejections.Why failing the astronaut eye exam became one of the defining obstacles of his life.How Mike trained his eyes to pass NASA’s vision requirements.Why the most successful people are not people who never fail.What “the right stuff” means beyond bravery, intelligence, or physical ability.Why teamwork, trust, and character matter so much in spaceflight.How imposter syndrome can change when you understand your role on a team.Why the odds only become zero when you give up.How private space companies could expand access to space. Timestamped Chapters: [04:53] NASA Checklists vs. Normal LifeMike explains why complex work in space can feel simpler than ordinary life when training, procedures, and support are in place. [07:13] Training for Spacewalks UnderwaterJames asks about NASA’s massive training pool, full-scale mockups, and how closely underwater training matches a real spacewalk. [08:33] The Overwhelming View of EarthMike says the work itself is trained into you, but the view of the planet from space is impossible to fully prepare for. [09:16] “The Earth Is a Planet”Mike describes seeing Earth as a fragile home surrounded by the rest of the universe. [11:32] Is There Life Somewhere Else?Mike explains why Hubble’s view of billions of galaxies makes it hard for him to believe Earth is the only place with life. [12:27] Why Hubble MattersJames and Mike talk about Hubble’s images, the telescope’s cultural impact, and why servicing it mattered. [14:03] The Hubble Deep FieldMike explains how Hubble found galaxies in a patch of sky that had seemed empty. [15:33] The Kid Who Wanted to Be an AstronautJames rewinds to Mike’s childhood: Neil Armstrong, the 1969 Mets, bad eyesight, fear of heights, and an impossible dream. [18:10] Losing Touch With the DreamMike reflects on how people can talk themselves out of what they really love because the path looks too hard. [18:28] Failing at MITJames compares his own graduate-school failure to Mike’s decision to keep going after failing his PhD qualifying exam. [20:43] Which Dreams Are Worth the Cost?Mike explains how he knew acting was interesting but space was something he was willing to suffer for. [23:20] Meaning, Public Service, and the Book’s Real ThemesMike says Spaceman became about dreams, persistence, the wonder of space, and the value of doing work that serves something larger. [26:29] Interest Plus MeaningJames identifies the pattern in Mike’s decisions: he pursued the work that combined personal interest with deeper purpose. [28:00] Finding the Path When There Is No MapMike explains why he chose to keep pursuing his PhD even though there were other possible routes to NASA. [30:06] Thirty Seconds of RegretMike remembers the advice to give yourself a short period of regret after failure, then move on. [31:19] The People Who Never Let Failure Stop ThemMike says the most successful people he has met are not people who never fail, but people who refuse to be stopped by failure. [35:20] Failing the NASA Eye ExamJames asks about the obstacle that seemed impossible to fix: Mike’s eyesight. [36:35] Applying to NASA Four TimesMike describes two early rejections, one interview, a failed medical exam, and the long road toward another chance. [39:10] “How Could I Have Given Up?”Mike explains why he could live with NASA saying no, but not with himself giving up. [40:28] Training His Eyes to See BetterMike finds a doctor, works through vision training, and eventually improves enough to pass the acuity requirement. [41:27] Getting to Space Was Not the EndJames notes that even after becoming an astronaut, Mike faced more setbacks, including the Columbia tragedy and the uncertainty around later Hubble missions. [43:07] Knowing When a Chapter Is OverMike explains why he eventually felt satisfied with his astronaut career and ready for the next phase. [43:48] Imposter Syndrome and TeamworkMike describes feeling like an imposter at MIT and NASA, and how belonging to a team helped him understand what he could contribute. [46:16] Redefining “The Right Stuff”James and Mike discuss why the real astronaut test is not swagger, but trust, character, and whether someone has your back. [49:11] Would You Trust This Person With Your Life?Mike explains the qualities NASA looks for beyond credentials: teamwork, reliability, humility, and character. [54:02] The Fourth Theme: Combinations of SkillJames points out that Mike’s power came from combining many abilities: astronaut, engineer, spacewalker, teacher, communicator, and author. [57:26] The Right Person Because He Wouldn’t Give UpMike says he may not have been the best spacewalker, but he was the person who would not quit when the Hubble repair became difficult. [01:00:14] The Odds Are Never Zero Until You QuitMike explains that near-impossible is not impossible—and the only way the chance disappears completely is if you give up. [01:01:05] The Future of SpaceflightMike talks about NASA, the International Space Station, Commercial Crew, SpaceX, Boeing, Blue Origin, Virgin Galactic, and private citizens in space. Additional Resources: Mike Massimino Official WebsiteMike Massimino BiographySpaceman by Mike MassiminoMike Massimino at Columbia EngineeringNASA: Mike Massimino Servicing the Hubble Space TelescopeNASA: STS-109 MissionNASA: STS-125 MissionNASA Science: Hubble Astronaut MissionsNASA Science: Hubble Servicing Mission 4NASA: Astronaut Mike Massimino Departs NASA for University Position See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

  5. 16 Jul

    Charles Duhigg Lost 45 Lbs on a GLP-1 | Why Food Noise Vanishes

    A Note from James: I’m doing a big experiment in my life. I recently started taking a GLP-1—tirzepatide, one of the so-called weight-loss drugs. But I didn’t start taking it specifically for weight loss. I had some blood work done for the first time in a long time, and there was a small indication that I might be pre-diabetic. My doctor suggested trying tirzepatide, and I wanted to understand what I was getting into. The first person I wanted to talk to was Charles Duhigg, author of The Power of Habit and Supercommunicators. Charles has been taking a GLP-1 for about two years, and he says it has changed his life. He has lost around 45 pounds, but what interested me most was not just the weight loss. It was the habit change. Charles explains that GLP-1s can quiet what people now call “food noise”—the constant background pull toward eating even when you are not actually hungry. When that noise quiets down, something interesting happens: you get a window where your old habits become more malleable. That is the key idea of this conversation. The drug may help you eat less, but the bigger opportunity is that it gives you a chance to build new routines around food, exercise, alcohol, sleep, and identity. And if you build those habits while the window is open, those habits may continue even after you stop taking the medication. We talk about food noise, cravings, the habit loop, keystone habits, stated versus revealed preferences, placebo effects, alcohol, sleep, exercise, blood sugar, identity, and whether GLP-1s are a lifelong drug or a tool for changing who you become. Episode Description: James is at the beginning of a GLP-1 experiment. Charles Duhigg is two years in. In this conversation, Charles explains what he has learned from taking tirzepatide and from studying GLP-1s through the lens of habit formation. He describes the first phase of public understanding around these medications as weight loss. Phase two, he argues, is about behavior change. The central concept is “food noise.” Charles describes it as the background craving that turns a basket of fries into an almost automatic behavior. You may not even notice the noise until it goes away. Once it quiets, the cue that normally triggers the habit loop weakens. That creates a temporary window where new habits can be built. James and Charles use the GLP-1 experience to revisit the basic habit loop: cue, routine, reward. They talk about why habits feel automatic, why willpower is often the wrong tool, and why successful behavior change depends on identifying the cue and replacing the routine while still satisfying the underlying reward. Charles also introduces the idea of GLP-1s as a catalyst for keystone habits. Eating less can make exercise easier. Drinking less can improve sleep. Better sleep can improve focus. Focus can improve work. One changed habit can set off a chain reaction. The conversation then becomes more philosophical: Who are we if one part of the brain says “I want to be healthy,” while another part of the brain keeps revealing different preferences through action? Charles explains the difference between stated preferences and revealed preferences, and how repeated behavior can shift identity. This is not a conversation about taking GLP-1s casually. It is a conversation about using a medical intervention deliberately, under appropriate medical guidance, as a chance to change the patterns that shape daily life. Editorial Note: This episode discusses prescription medications, including tirzepatide and semaglutide, as well as personal experiences with GLP-1 drugs. It should not be treated as medical advice. GLP-1 medications can have side effects and risks, including gastrointestinal symptoms, dosing concerns, and contraindications for some patients. They should be used only under the supervision of a qualified medical professional. Any decision to start, stop, adjust, or combine medications should be made with a clinician. James and Charles also discuss personal experience, habit change, appetite, alcohol cravings, and identity. Individual responses to these medications vary. What You’ll Learn: Why Charles believes GLP-1s are entering “phase two”: not just weight loss, but habit change.What “food noise” feels like—and why people often do not notice it until it disappears.How GLP-1s may create a temporary “habit window” where old routines become easier to change.Why the habit loop—cue, routine, reward—matters when trying to change eating behavior.Why people often regain weight after stopping GLP-1s if they have not built new habits.How keystone habits can create a chain reaction across food, exercise, alcohol, sleep, and focus.Why micro habits may work better than a full lifestyle overhaul.How stated preferences and revealed preferences shape identity.Why eating less can make exercise easier, and why exercise can reinforce healthier choices.Why tracking behavior may be essential while taking a GLP-1.How placebo, alter egos, and rituals may influence identity and performance.Why the goal is not just losing weight, but becoming the kind of person whose habits support health. Timestamped Chapters: [03:36] James Begins His GLP-1 Experiment James explains his early experience, including confusion between medication side effects and a bout of COVID. [04:16] Charles’s Two-Year Experience Charles describes taking tirzepatide, losing roughly 45 pounds, and why the biggest changes came months into the process. [05:38] Phase One vs. Phase Two of GLP-1s Phase one was about appetite and weight loss. Phase two, Charles argues, is about habits that can last. [06:42] The Habit Window How GLP-1s can quiet food noise and create a period where eating habits become more malleable. [07:21] COVID, Side Effects, and Early Signals James explains why his first few weeks were hard to interpret and why he is still figuring out what the medication is doing. [09:00] What Food Noise Actually Feels Like Charles uses the example of a basket of fries to explain cravings, cues, and automatic eating. [09:55] The Habit Loop: Cue, Routine, Reward Charles revisits the framework from The Power of Habit and applies it directly to food cravings. [10:42] How GLP-1s Interrupt the Cue The fries are still there, but the craving does not activate in the same way. [11:40] What GLP-1s Do in the Body and Brain Charles explains what researchers know about gastric emptying, glucagon-like peptides, and what remains uncertain about the brain. [12:43] What Happens When You Stop Why the medication alone may not be enough if old habits return after discontinuation. [13:36] Pleasure, Food, Alcohol, and Anhedonia Charles discusses reduced pleasure from food and alcohol, while separating clinical findings from broader claims about losing joy in life. [15:54] Why Charles Stayed With It Early changes were not dramatic weight loss, but a growing feeling that eating became more of a choice. [16:40] Eating as a Keystone Habit How changing food behavior can trigger changes in exercise, alcohol, sleep, focus, and work. [19:31] Why Structure Matters Charles explains why tracking and guided habit systems can help people see patterns they might miss on their own. [20:32] What Changes Physically Over Time Slower stomach emptying, feeling full longer, more stable blood sugar, and gradual changes in appetite. [21:43] Stated Preferences vs. Revealed Preferences Why one part of the brain says “I want to change,” while another part watches what you actually do. [23:22] Identity Change and Habit Formation How repeated behavior can teach the brain, “I am the kind of person who eats this way” or “I am the kind of person who exercises.” [24:16] Placebo, Belief, and Becoming the Person You Want to Be James and Charles explore whether placebo effects may work partly by changing identity. [28:07] Alter Egos, Athletes, and Rituals The conversation turns to Kobe Bryant, Michael Phelps, and how pre-performance routines can cue a desired identity. [29:15] Start With Micro Habits Charles explains why small behavior changes can compound more effectively than trying to overhaul an entire life at once. [30:40] Charles’s First Micro Habits Drinking less, eating fewer fries, stopping when full, and choosing healthier meals without relying on willpower. [31:24] Feeling Full for the First Time Charles describes the surprising experience of leaving food unfinished because his body had had enough. [33:03] Why the Stomach Shrinks The medication does not shrink the stomach directly; eating less over time changes how much food the body expects. [33:21] Why Slower Stomach Emptying Helps James asks why a weight-loss drug would slow digestion instead of speeding metabolism. [35:00] The Cumulative Effect Why the most visible changes often appear after several months, once habits, body size, and identity begin reinforcing each other. [37:03] Is a GLP-1 a Lifelong Drug? Charles explains what research and personal experience suggest about stopping, restarting, and maintaining results. [38:56] James’s Health Motivation James explains that his motivation is not primarily weight loss, but a desire to respond to possible pre-diabetic markers. [39:36] Why Attitude Is Not Enough Charles argues that wanting to be healthy helps, but habit change still requires structure. [40:02] What Changed at Home Charles explains how his family’s food did not need to change, even though his own choices and portions did. [41:02] Weight, Body Composition, and Pre-Diabetes Why blood sugar, insulin resistance, fat, and muscle matter more than the scale alone. [42:38] Semaglutide, Tirzepatide, and What Comes Next James and Charles compare different GLP-1 medications and discuss how newer drugs may work through multiple receptors. [44:27] Will Charles Stop Taking It? Charles explains why he may eventually discontinue the medication, but values having more choice over weight and behavior. [45:24] Blood Work, Sn

    Charles Duhigg Lost 45 Lbs on a GLP-1 | Why Food Noise Vanishes
  6. 12 Jul

    From the Archive: Garry Kasparov on Deep Blue, Fear, and the Future of AI

    A Note from James: I’ve done several hundred podcasts, but if people asked me who were the one or two people I most wanted to have on the show, Garry Kasparov would be at the top of the list. He was World Chess Champion for twenty years, and I’ve followed his career since the early ’80s. His book, Deep Thinking, tells the story of his matches against Deep Blue, but it’s really about what may be the most important relationship of this century: humans and machines. Episode Description: In this From the Archive episode, James talks with Garry Kasparov in his first appearance on the show. Kasparov looks back at the matches that shaped him: his comeback from a 5–0 deficit against Anatoly Karpov, the psychological side of elite competition, and his historic showdown with IBM’s Deep Blue. They also talk about why a computer beating a world champion did not settle the question of intelligence, how technology changes the kind of work people do, and why fear of making a mistake often causes the mistake itself. Kasparov shares what chess taught him about preparation, adaptability, mentorship, and making decisions when there is no obvious right move. This conversation was recorded in 2017; the political discussion reflects that moment in time. What You’ll Learn: Why adaptability—not strength or intelligence alone—is what helps people survive major change.How Kasparov used a 5–0 deficit against Karpov to build confidence, patience, and resilience.Why fear can paralyze decision-making when the stakes are high.How to think about AI and automation as forces that create new possibilities as they eliminate old roles.Why mentors, pattern recognition, and disciplined practice matter in chess and every other field. Timestamped Chapters: [02:05] Fear, choices, and the danger of paralysis[03:06] James meets Garry Kasparov[05:11] Deep Thinking and the question of machine intelligence[06:35] Growing up with chess in the Soviet Union[10:11] Botvinnik, preparation, and training through distraction[12:30] Facing Karpov and falling behind 5–0[20:20] The value of adapting under pressure[23:53] Psychology and what separates champions[26:16] Kasparov’s playing style and coaching Magnus Carlsen[30:18] Why Deep Blue forced Kasparov to change his game[31:25] AI, automation, and the future of work[38:38] What happened in the Deep Blue matches[42:32] Chess, Go, and the limits of human accuracy[46:08] Fear, risk, and making better decisions[48:56] The Kasparov Chess Foundation and education[57:08] Russia, Putin, and political opposition in 2017[63:46] How to adapt to technological change Additional Resources: Deep Thinking: Where Machine Intelligence Ends and Human Creativity BeginsWinter Is Coming: Why Vladimir Putin and the Enemies of the Free World Must Be StoppedIBM’s history of Deep BlueKasparov Chess Foundation See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

  7. 8 Jul

    Frank Miller on Push the Wall, Batman, and Having No Plan B

    A Note from James: This is a very special episode for me. There have only been a few times in the history of this podcast when I’ve had the chance to sit down with one of my heroes. This is one of those times. Frank Miller is one of the most important storytellers of my life. When I first picked up Batman: The Dark Knight Returns in 1986, it completely changed what I thought comics could be. This wasn’t just another Batman story. It was a revolution. Frank took Batman out of the colorful, campy world I grew up with and turned him into something darker, mythic, terrifying, and psychologically real. There is a comic book industry before The Dark Knight Returns, and there is a comic book industry after The Dark Knight Returns. Every Batman movie since then carries Frank’s fingerprints in some way. But it wasn’t just Batman. Frank changed Daredevil. He created Ronin. He created Sin City. He showed that comics could handle adult stories, painful arcs, crime, tragedy, mythology, obsession, and moral ambiguity. But what matters most to me is that Frank is a master storyteller. And I love storytelling. Whether it’s books, podcasts, articles, comics, or just how we make sense of our lives, story is everything. So getting to sit down with Frank Miller and talk about Batman, myth, creativity, mentorship, discipline, and his new book, Push the Wall: My Life, Writing, Drawing, and the Art of Storytelling, was a dream come true. This was my first in-person podcast in years. Jay drove up from Atlanta. I flew into the city. And yes, I brought my copy of The Dark Knight Returns for Frank to sign. Episode Description: Frank Miller didn’t just write and draw some of the most influential comics of the modern era. He changed the grammar of comics. In this conversation, James sits down with Miller to talk about Batman: The Dark Knight Returns, Daredevil, Ronin, Sin City, and Miller’s new book, Push the Wall. The conversation begins with Batman, but quickly becomes a larger discussion about how characters become myths. For Miller, Batman was never just a rich detective in a costume. The material was already there from the beginning: a child witnessing the murder of his parents, growing up without powers, building himself into a force through discipline, intelligence, and obsession. Miller’s goal was to pull that core truth out and make Batman stand beside older pulp and mythic figures like Zorro, The Shadow, and the hard-edged heroes of crime cinema. James and Frank also talk about how myths are built around simple central values. Superman is hope. Batman is justice, vengeance, effort, and fear. The art is not in making those ideas complicated. The art is in placing them inside a human context so they feel emotionally true. The discussion moves into the craft of comics itself: page layouts, panel borders, visual rhythm, and how the pictures carry most of the story. Miller reflects on the influence of Jack Kirby, Neal Adams, Denny O’Neil, Japanese samurai films, martial arts movies, Greek tragedy, Jean Giraud/Moebius, Lone Wolf and Cub, and the creative power of combining worlds that do not obviously belong together. They also talk about mentorship. Miller describes calling Neal Adams from the phone book, bringing him drawings, and enduring brutally honest criticism. That toughness, he says, was part of the training. To survive as an artist, you need egoism without egotism: enough belief to keep coming back, but enough humility to keep learning. The episode closes with practical advice for young artists today: go to conventions, build the strongest portfolio you can, seek out hard criticism, don’t chase only the biggest titles, protect your original ideas, and look for “losers” you can make great. What You’ll Learn: Why Frank Miller wanted Batman to become a myth, not just another superhero.How The Dark Knight Returns helped move comics toward darker, more adult storytelling.Why Batman’s lack of superpowers is exactly what makes him compelling.How mythic characters are built around simple core themes like hope, vengeance, justice, or discipline.Why comics are not just written stories with pictures, but a visual storytelling machine.How Miller learned from Jack Kirby, Neal Adams, Denny O’Neil, samurai films, noir, Greek tragedy, and European comics.Why creativity often comes from combining unrelated influences.What Miller means by “egoism, but not egotism.”Why young artists should seek out hard lessons instead of easy praise.How to enter comics today without giving away original work too early.Why determination, stamina, and a lack of Plan B shaped Miller’s career.What Miller is working on next, including a new Western-style Sin City story. Timestamped Chapters: [03:41] Meeting Frank MillerJames begins by holding up Batman: The Dark Knight Returns and asking what it means to be known through one defining work.[04:00] Before and After The Dark Knight ReturnsWhy James sees Miller’s Batman as a dividing line in comic book history.[05:07] Turning Batman Into a Psychological ConditionJames asks how Miller transformed Batman from a campy hero into something darker, mythic, and terrifying.[05:49] Batman as MythFrank explains that his first impulse was to make Batman stand with figures like The Shadow, Zorro, and the hard-edged heroes of crime cinema.[06:37] Pulling Comics Out of ChildhoodMiller describes his desire to push comics into adolescence and beyond the conventions of disposable monthly stories.[06:59] The Origin Was Always ThereWhy Batman’s trauma, lack of powers, and self-made discipline were already embedded in the character from the beginning.[07:50] Superman Descends, Batman RisesFrank contrasts Superman as a figure of light with Batman as something that comes up from the darkness.[08:44] What Makes a Character Mythic?Miller explains that great characters usually have a simple central theme: hope, justice, vengeance, effort, or fear.[10:30] King Arthur, Luke Skywalker, and the Power of ObjectsThe conversation turns to swords, lightsabers, utility belts, and how mythic symbols carry stories across generations.[11:54] Breaking the PageJames and Frank discuss how Kirby, Neal Adams, and others shattered conventional panel layouts before Miller pushed those techniques further.[12:35] A Tradition of RevolutionFrank explains why creativity means breaking a few eggs while still working inside a lineage.[13:00] When the Page Tells the StoryHow panel size, shape, and visual composition can carry emotional meaning without words.[14:10] What Would Frank Do With Batman Now?Miller says the point is not to reinvent Batman for novelty’s sake, but to find a good story.[15:00] Moving Daredevil Into Hell’s KitchenJames asks how Miller brought his own New York experience into Daredevil’s world.[15:45] Fear, Editors, and Media ConglomeratesFrank reflects on how creative fear moves through artists, editors, bosses, and corporate structures.[16:17] Are New Comic Stories Still Possible?Miller argues that the talent and creative energy are still there, even if it does not always come from predictable places.[17:40] How Comics Survived Their Own DeathsFrank traces comic books from the attacks of the 1950s to Marvel, underground comics, and the direct market.[19:30] What Young Artists Need TodayWhen James asks what skill matters beyond drawing and storytelling, Miller answers: determination.[20:01] No Plan BFrank explains that he never had a concept of failure because comics were what he had wanted to do since his earliest memories.[20:47] Writing vs. StorytellingWhy, in comics, most of the storytelling happens in the pictures.[21:00] Neal Adams and the Hard LessonsMiller remembers calling Neal Adams from the phone book and receiving tough critiques that tested his character.[22:34] Egoism, Not EgotismFrank explains the balance an artist needs: enough ego to return after criticism, but not so much that they stop learning.[22:51] Stealing From the GreatsWhy artists must study and learn from earlier practitioners rather than pretending genius arrives fully formed.[23:47] Batman Is Possessed, Not ObsessedFrank corrects James’s description of Batman and explains that Batman is filled with an eternal force.[24:50] Daredevil, Samurai, Crime, and Greek TragedyHow Miller fused martial arts films, ninja stories, crime movies, and Greek tragedy into his Daredevil run.[27:01] Stick, Elektra, and the Sensei ArchetypeJames and Frank trace the mentor-student relationship through Daredevil, samurai stories, and mythic training narratives.[27:47] Lone Wolf and Cub, Moebius, and RoninHow Forbidden Planet exposed Miller to Japanese and European comics, leading to the hybrid world of Ronin.[28:35] The Power of IntersectionsWhy combining Westerns, samurai stories, science fiction, noir, and mythology can create something new.[30:08] Discipline vs. ChaosJames identifies a recurring theme in Miller’s work: taking chaos and molding it into purpose.[30:40] Batman Becomes the FatherFrank explains the final image of The Dark Knight Returns: the orphan becoming the father.[31:24] Why So Many Heroes Are OrphansMiller says the lone child against the elements is at the heart of heroic storytelling.[32:36] Guilt, Control, and Batman’s Unhealed WoundJames and Frank discuss whether Batman is driven by guilt or by the need to take control after childhood trauma.[33:43] Pushing Batman to the ExtremeWhy Miller made the Batmobile a tank and amplified the character’s core qualities.[33:50] How Frank Would Start TodayMiller advises young artists to attend conventions, show their work, use the internet, and seek honest feedback.[34:36] Seek Hard CriticismWhy young creators should avoid people who only make them feel good.[34:59] Don’t Chase the Biggest TitlesMiller advises artists to look for overlooked characters—or better yet, create something themselves.[35:21] Find a Loser and Do It RightA practical creative strategy: identify

    Frank Miller on Push the Wall, Batman, and Having No Plan B
  8. 3 Jul

    Dr. David Sinclair: The First Human Trial of an Age-Reversal Therapy

    A Note from James: I’ve been obsessed with anti-aging and longevity science for a long time. I’ve had many longevity researchers on the podcast, but this episode feels different because something we’ve been discussing for years has now moved into human trials. David Sinclair first came on the show in 2019, when his book Lifespan was published. He’s a professor of genetics at Harvard Medical School, and that first conversation changed how I lived. I started experimenting with intermittent fasting, paid much more attention to sleep, and began researching many of the supplements and lifestyle changes he discussed. But the most important idea David talked about wasn’t a supplement. It was the possibility of reversing cellular age using Yamanaka factors—genes that can reset the instructions cells use to function. At the time, nobody knew whether this could be done safely without causing cancer or making cells lose their identities. Now, a therapy based on three of those factors has entered its first human clinical trial. The initial target is age-related damage to the optic nerve, including open-angle glaucoma and non-arteritic anterior ischemic optic neuropathy. The trial is designed primarily to evaluate safety, but researchers will also measure visual function. David explains how this technology worked in mice and nonhuman primates, why the eye was chosen as the first organ, and how the same approach might eventually be applied to the liver, lungs, joints, skin, and brain. We also cover the practical questions people always ask him: NMN, NAD, metformin, berberine, testosterone, growth hormone, diet, fasting, sleep, exercise, and what David himself has started—or stopped—taking. This is still experimental science. Nobody yet knows whether the animal results will translate into meaningful benefits for humans. But for the first time, researchers are beginning to test that question directly. About Lifespan:  Dr. David Sinclair founded Lifespan to deliver clear, science-backed health insights that help people live longer, more vibrant lives. He's now building the world's largest community dedicated to extending human longevity well beyond today’s limits. Join early access at lifespan.com.  New episodes of Lifespan with Dr. David Sinclair -- the #1 health and wellness podcast in its first season -- are now available on YouTube, Spotify, Apple Podcasts, and Lifespan.com. Episode Description: For years, longevity researchers have looked for ways to slow the biological processes associated with aging. Dr. David Sinclair and his collaborators are now testing a more ambitious possibility: whether damaged human cells can be restored to a younger, more functional state. The experimental therapy, ER-100, uses controlled expression of three transcription factors—OCT4, SOX2, and KLF4, collectively known as OSK. These are three of the four Yamanaka factors originally used to transform adult cells into pluripotent stem cells. Turning on all four factors can erase too much of a cell’s identity and has produced tumors and fatal outcomes in animal experiments. Sinclair’s team found that removing one factor, c-MYC, allowed cells to regain younger patterns of gene expression without completely returning to a stem-cell state. In preclinical studies, OSK restored youthful epigenetic patterns, promoted optic-nerve regeneration, and reversed vision loss in mouse models. Life Biosciences, a company Sinclair co-founded, has now moved the technology into a first-in-human Phase 1 trial involving people with open-angle glaucoma or non-arteritic anterior ischemic optic neuropathy. David explains how the therapy is delivered directly into the eye and activated using doxycycline, allowing clinicians to control when and for how long the genes are expressed. He also describes the development path that could follow if the treatment proves safe, including therapies targeting the liver and other organs, as well as future medicines that may reproduce similar effects without gene delivery. The conversation then turns to interventions available today. David distinguishes between promising research and claims that have moved ahead of the evidence, discussing NMN, injected NAD, growth hormone, testosterone, taurine, nattokinase, metformin, berberine, and nootropics. Throughout the episode, he emphasizes that no supplement has been shown to reproduce the effects researchers are attempting to achieve through partial epigenetic reprogramming—and that many of the most dramatic claims circulating online remain unsupported. Editorial Note: ER-100 is an investigational therapy. Authorization to begin a clinical trial does not mean the treatment has been proven safe or effective, nor has it been approved for clinical use. The Phase 1 study is primarily evaluating safety and tolerability, with additional measurements of visual function. Results from mice and nonhuman primates do not establish that the therapy will restore vision or reverse biological aging in people. The discussion of supplements, prescription medications, hormones, and lifestyle practices reflects the speakers’ personal views and interpretation of the research. It should not be treated as individualized medical advice. Prescription drugs, hormones, supplements, and experimental longevity treatments should be discussed with an appropriately qualified healthcare professional. What You’ll Learn: How partial epigenetic reprogramming differs from completely resetting a cell into a stem cell.Why researchers selected three Yamanaka factors—OCT4, SOX2, and KLF4—instead of using all four.What ER-100 is designed to do and why the first human trial focuses on the optic nerve.How doxycycline acts as an external switch controlling when the therapeutic genes are expressed.What Phase 1 researchers will measure and what would need to happen before ER-100 could become an approved treatment.Why the eye provides a useful starting point for testing cellular rejuvenation.What animal studies suggest about restoring vision, memory, liver function, joints, and skin.Why delivering rejuvenation therapies throughout the body is more difficult than treating one localized organ.The difference between oral NMN supplementation and intravenous or subcutaneous NAD.What current research does—and does not—show about growth hormone, testosterone, taurine, metformin, and berberine.Why muscle, exercise, sleep, diet, glucose regulation, and inflammation remain important even if rejuvenation therapies eventually succeed.How Sinclair’s laboratory is searching for pills and small molecules that could mimic epigenetic reprogramming without gene therapy. Timestamped Chapters: [04:53] The First Human Trial Begins David discusses ER-100, FDA authorization, and the treatment of open-angle glaucoma and ischemic optic neuropathy.[06:52] What Are the Yamanaka Factors?How reprogramming genes can reset cellular instructions—and why using all four factors can be dangerous.[08:56] Reversing Vision Loss and Memory Problems in AnimalsDavid describes studies involving the eyes, brain, skin, kidneys, liver, and age-related cognitive decline.[10:09] Why Four Factors Can Cause CancerThe difference between restoring youthful function and erasing a cell’s identity completely.[10:54] The Three-Gene BreakthroughHow Sinclair’s student Yuancheng Lu persisted through years of failure and identified the OSK combination.[12:03] Pulsing the Genes vs. Leaving Them ActivatedEarlier four-factor experiments required intermittent activation, while OSK showed a different safety profile in animal eyes.[13:36] The Doxycycline Safety SwitchHow clinicians may use an antibiotic to activate and deactivate the therapy after it has been delivered.[14:51] Treating the Cause Instead of the SymptomsDavid argues that restoring younger tissue function could allow the body to repair damage associated with age-related disease.[16:02] Why the Trial Starts With the EyeLocalized delivery reduces systemic exposure and makes visual changes easier to observe and measure.[16:50] Can the Therapy Reach the Brain and the Rest of the Body?The challenges of distributing gene-based treatments evenly across organs and through the blood-brain barrier.[18:25] What the Phase 1 Trial Will MeasureSafety, tolerability, visual function, and the possibility of an accelerated development path.[20:36] Expanding Beyond GlaucomaWhy each organ may require a different delivery vehicle—and how the liver could become another early target.[21:38] How Shinya Yamanaka Found the Original Four FactorsThe trial-and-error process that turned adult cells into induced pluripotent stem cells.[22:38] How ER-100 Is DeliveredDavid explains the OSK genes, the AAV delivery system, doxycycline activation, and why manufacturing is expensive.[25:21] When Could the Treatment Become Available?David gives his most optimistic development timeline and discusses parallel programs targeting other organs.[27:31] NMN, NAD, Sirtuins, and the Information Theory of AgingHow declining NAD levels may affect cellular defenses and the regulation of gene expression.[31:34] Oral NMN vs. Injected NADWhy David believes oral supplementation currently has more rigorous evidence than NAD injections.[32:20] Longevity Misinformation OnlineDavid explains why he is restarting his show and warns against confident recommendations unsupported by research.[32:41] Growth Hormone and LifespanWhy growth hormone may improve certain functions but has not been shown to slow aging or extend human life.[34:05] Testosterone, Muscle Mass, and Healthy AgingPotential benefits for maintaining muscle—and why testosterone alone should not be considered a longevity treatment.[36:01] Taurine, Nattokinase, and Changing Your MindWhy David stopped taking taurine regularly and what prompted his interest in nattokinase.[37:30] David’s Current Diet and His 86-Year-Old FatherLower meat and cheese consumption, little alcohol, e

    Dr. David Sinclair: The First Human Trial of an Age-Reversal Therapy

About

James Altucher interviews the world's leading peak performers in every area of life. But instead of giving you the typical success story, James digs deeper to find the "Choose Yourself" story - these are the moments we relate to... when someone rises up from personal struggle to reinvent themselves. The James Altucher Show brings you into the lives of peak-performers: billionaires, best-selling authors, rappers, astronauts, athletes, comedians, actors, and the world champions in every field, all who forged their own paths, found financial freedom and harnessed the power to create more meaningful and fulfilling lives.

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