Endgame with Amanda Cassatt

What if you could choose your child before they’re born?Noor Siddiqui, founder of Orchid, joins Amanda Cassatt to explore one of the most profound frontiers in biotech: genetically screening and selecting embryos during IVF. At the intersection of science, ethics, and the human desire for legacy, this conversation asks how far we’re willing to go to optimize health, reduce suffering, and rethink what it means to become a parent.They examine the promises and perils of “super babies,” a futuristic term quietly approaching reality. Once reserved for preventing rare genetic diseases, embryo testing is now exploring polygenic scoring, offering parents insight not only into potential health outcomes but also into cognitive traits such as IQ. With that insight comes questions about eugenics, equity, and where the line lies between informed choice and engineered outcomes.Noor shares how the burden of genetic disease shapes families and why she believes informed embryo selection can empower rather than control. Amanda and Noor also discuss the fertility crisis, the economic and cultural shifts reshaping family planning, and what it would take to build a world where having a child doesn’t demand superhuman effort or superhuman genes.TIMESTAMPS:00:00 Introduction to Orchid and IVF Technology02:57 Understanding Genetic Testing in Embryos06:08 The Concept of 'Super Babies' and Genetic Blessings09:03 Selection Pressure in Embryo Choices12:02 The Burden of Genetic Diseases14:43 Ethical Considerations in Genetic Selection17:49 The Future of Reproductive Technology20:49 Enhancements vs. Remediation in Genetic Technology23:36 The Role of Cost in IVF Accessibility26:32 The Future of Genetic Editing and CRISPR29:40 Conclusion and Future Outlook40:57 The Future of Reproductive Technology44:21 The Global Fertility Crisis48:40 Cultural Shifts in Parenthood51:24 The Purpose of Life and Parenthood55:53 Nature vs. Nurture in Child Development59:47 Personal Aspirations and Family Planning01:02:09 The Ethics of Genetic Selection01:08:54 Existential Questions and Identity

Crypto began as a rebellion against banks, bailouts, and surveillance. But what happens when the same forces it tried to outrun start reshaping the industry from within?Megan Knab, founder of Franklin, joins Amanda Cassatt on Endgame to examine where crypto may be drifting off course. She raises concerns about what happens when privacy disappears, how unbanking and financial exclusion play out in practice, and why stablecoins, if implemented incorrectly, could entrench the very systems crypto was meant to disrupt.From Tornado Cash and the prosecution of developers, to the ethical standards builders should hold themselves to, the conversation circles back to what it means to take cypherpunk values seriously in 2025. For Megan, that extends beyond manifestos and protocols, it’s about how anyone involved in crypto can carry those values forward in practice, from the tools they use to the way they choose to build, transact, and communicate.The lingering question: if crypto repeats the mistakes of legacy finance, what was the point of building it at all?TIMESTAMPS: 00:00 The Coinbase Military Parade Controversy03:02 The Origins of Cryptocurrency and Its Antithetical Nature to Government05:39 The Dangers of Government Involvement in Crypto08:49 The Unbanking Phenomenon and Its Implications11:52 Corporate Compliance and the Erosion of Cypherpunk Values14:51 Standards for Cryptocurrency Companies17:34 The Role of Privacy in Financial Transactions20:39 The Impact of Institutionalization on Crypto's Goals27:47 The Cypherpunk Values and Their Evolution31:33 Privacy Technology: Tornado Cash and Its Implications39:59 Stable Coins: Bridging Traditional Finance and Crypto45:36 The Future of Privacy in a Centralized World

➡️Like this episode? Leave a review: https://ratethispodcast.com/endgameIt feels like crypto adoption is moving at lightning speed, but is anyone still "in it for the tech"?Eddy Lazzarin, CTO of a16z crypto, joins Amanda Cassatt on Endgame to explore the growing influence of capital markets, and government and regulatory access, in the current landscape, as well as the specific breakthroughs he anticipates in AI and privacy that would make technology once again the driver of progress.Touching on Tornado Cash, they discuss whether privacy technology has a future in an environment where governments are active players in the industry, the impact of the coming massive wave of asset tokenization, and how Eddy expects AI and crypto will actually converge and find product-market fit.From his vantage point at the intersection of new technology and venture investing, Eddy reflects on what real innovation looks like when the narrative is shaped as much by capital as it is by code.This conversation offers a window into how one of crypto’s most influential firms evaluates technology, risk, and opportunity.➡️Talking Points: 00:00 Understanding the Role of CTO at A16Z02:56 A16Z's Evolving Perspective on Venture Capital05:56 The Impact of Regulation on Technology Innovation08:46 Navigating the Intersection of Traditional Finance and Crypto11:46 The Future of Corporate Integration with Blockchain14:43 The Coexistence of Legacy Systems and New Technologies17:43 The Role of AI in Bridging Old and New Systems29:27 Trusting AI: Expanding Boundaries32:31 The Privacy Paradigm: Current Challenges and Future Solutions42:49 Navigating the Future: Privacy, Compliance, and User Experience55:31 Envisioning the Future: A Non-Custodial Financial Ecosystem➡️Show Links: Follow Eddy: https://x.com/eddylazzarinSubscribe to Endgame: https://www.youtube.com/@endgamepodcast  Amanda on X:  https://x.com/amandacassatt  Serotonin on X: https://x.com/serotonin  Endgame on Spotify: https://open.spotify.com/show/6iSvbKOJWoEPiAoGmiulkd   Endgame on Apple Podcasts: https://podcasts.apple.com/us/podcast/endgame-with-amanda-cassatt/id1801809440  Substack: https://substack.com/@UCInZsV3L1nDGoFjxoNUnPQQ

How decentralized AI will win, according to NEAR Founder Illia Polusukhin.Illia Polosukhin, co-founder of NEAR Protocol, joins me on the latest episode of Endgame to challenge everything we think we know about AI.In this episode, Illia explains: - The dangers of AI being monopolized by corporate interests- Why a user-owned, decentralized model is the way forward- The role of blockchain and confidential computing in building a system that prioritizes privacy, transparency, and true user empowermentTIMESTAMPS: 00:00 The Future of AI and the Internet02:57 The Dangers of Centralized AI06:07 User-Owned AI and Decentralization08:53 Challenges in AI Model Creation11:57 Blockchain's Role in AI Infrastructure14:57 Confidential Computing and User Privacy17:52 Data Center Dynamics and AI Demand21:00 Autonomous Agents and Their Potential23:54 The Spectrum of AI: Abundance vs. Doom26:53 The Future of Work and Automation29:42 The Role of Crypto in AI Development32:46 Real-World Applications of Blockchain and AI35:38 The Path Forward for Decentralization38:41 The Intersection of AI and Cybersecurity41:51 The Vision for a Utopian Future44:41 The Challenges Ahead for AI and CryptoRESOURCES:Follow Illia: https://x.com/ilblackdragonSubscribe to Endgame: https://www.youtube.com/@endgamepodcast  Amanda on X:  https://x.com/amandacassatt  Serotonin on X: https://x.com/serotonin  Endgame on Spotify: https://open.spotify.com/show/6iSvbKOJWoEPiAoGmiulkd   Endgame on Apple Podcasts: https://podcasts.apple.com/us/podcast/endgame-with-amanda-cassatt/id1801809440  Substack: https://substack.com/@UCInZsV3L1nDGoFjxoNUnPQQ

What does crypto look like when you strip away the noise and just follow the data?Fredrik Haga, co-founder of Dune, joins Amanda Cassatt for a conversation that cuts through the headlines and into the heart of what’s actually happening onchain. From the slow decline of NFTs to the real traction behind stablecoins and RWAs, Frederik offers an inside look into crypto’s shifting center of gravity and brings the data to prove it.This episode moves charts as Frederik shares the personal cost of building a billion-dollar company in Norway and why a tax on unrealized gains forced him to leave the country he was building in. This is a conversation about what's really working in crypto and what's still getting in the way.TIMESTAMPS:00:00 On-Chain Metrics and Market Dynamics03:03 The Rise and Fall of NFTs05:55 Stablecoins and Real World Assets08:54 Layer 2 Solutions and Their Impact11:56 The Middle Class of Crypto14:52 Mismatches Between Hype and Reality17:53 AI and Crypto Intersections20:54 The Founder’s Journey: Building Dune23:41 Norway's Economic Challenges and Opportunities29:40 Governance and Innovation in CryptoRESOURCES:Follow Fredrik Haga: https://x.com/hagaetcSubscribe to Endgame: https://www.youtube.com/@endgamepodcast  Amanda on X:  https://x.com/amandacassatt  Serotonin on X: https://x.com/serotonin  Endgame on Spotify: https://open.spotify.com/show/6iSvbKOJWoEPiAoGmiulkd   Endgame on Apple Podcasts: https://podcasts.apple.com/us/podcast/endgame-with-amanda-cassatt/id1801809440  Substack: https://substack.com/@UCInZsV3L1nDGoFjxoNUnPQQ

Ethereum has always been the foundation for the next financial system.Amanda Cassatt sits down with Grant Hummer, co-founder of Etherealize, to explore why Ethereum continues to be misunderstood, especially by institutions, and what it will take to change that.They go deep on Ethereum’s cultural and economic DNA, from early narrative missteps to what makes ETH uniquely positioned to dominate tokenization and programmable finance. Grant explains why rollups matter, how proof-of-stake has changed the game, and what Ethereum’s endgame could look like if it wins.Then they turn to Bitcoin. Grant lays out the case for why BTC, despite its mythology, faces real threats from its security model to the looming problem of quantum resistance. As Ethereum continues evolving while Bitcoin stands still, what happens next?This episode makes one thing clear: Ethereum isn’t playing catch-up, it’s playing for keeps.TIMECODES:00:00 The Genesis of Etherealize02:53 Bridging the Gap: Educating Wall Street on Ethereum05:53 Understanding Ethereum's Value Metrics09:11 The Role of Rollups in Ethereum's Ecosystem11:56 The Bull Case for Ethereum: Digital Oil vs. Digital Gold15:09 Ethereum's Future: Tokenization and Market Dynamics18:07 The Battle for Developer Hearts and Minds21:04 Navigating Regulatory Landscapes23:59 The Shift to Proof of Stake: A New Era for Ethereum27:00 Bitcoin vs. Ethereum: The Future of Digital Assets29:59 The Road Ahead for Etherealize and EthereumRESOURCES:Follow Grant: http://x.com/gphummer?lang=enSubscribe to Endgame: https://www.youtube.com/@endgamepodcast  Amanda on X:  https://x.com/amandacassatt  Serotonin on X: https://x.com/serotonin  Endgame on Spotify: https://open.spotify.com/show/6iSvbKOJWoEPiAoGmiulkd   Endgame on Apple Podcasts: https://podcasts.apple.com/us/podcast/endgame-with-amanda-cassatt/id1801809440  Substack: https://substack.com/@UCInZsV3L1nDGoFjxoNUnPQQ

What if the real threat to humanity isn’t death, but the belief that life needs to mean something?In this episode of Endgame, Amanda Cassatt and Bryan Johnson explore the architecture of a world where death is optional and meaning might be too. Rejecting first-principles thinking, the problem-solving method rooted in historical patterns and known truths, Bryan proposes zeroth-principles thinking: a framework that imagines human existence beyond inherited assumptions. In this future, meaning may vanish along with our drive for ambition, legacy, and identity.They discuss why accomplishment might be nothing more than preparation for death, how attachment to power, wealth, and status could undermine our survival, and why it’s easier to imagine the end of the world than the end of capitalism. Bryan also explores a world beyond game theory, where humanity disables evolutionary instincts like competition and status-seeking, treating them as flaws in our biological code.This is a philosophical autopsy of mortality, meaning, and the psychological machinery we’ve built around being human.TIMESTAMPS: 02:56 Debating Life and Death: The Immortality Argument06:06 The Case Against Immortality: Societal Implications08:50 Wealth, Power, and the Future: A Generational Perspective11:51 The Role of Legislation in a Changing Society14:34 The Nature of Meaning: Life, Death, and Legacy17:35 The Evolution of Human Behavior: Risk and Sacrifice20:46 Post-Meaning: Redefining Existence in a New Era23:46 The Future of Innovation: Aging and Stagnation26:27 The Role of AI: Navigating Uncertainty and Change29:26 The Dilemma of Existence: Freedom vs. Attachment32:35 The Final Thoughts: Embracing Uncertainty and ChangeRESOURCES:Subscribe to Endgame: https://www.youtube.com/@endgamepodcast Amanda on X: https://x.com/amandacassatt Serotonin on X: https://x.com/serotonin Endgame on Spotify: https://open.spotify.com/show/6iSvbKOJWoEPiAoGmiulkd Endgame on Apple Podcasts: https://podcasts.apple.com/us/podcast/endgame-with-amanda-cassatt/id1801809440 Substack: https://substack.com/@UCInZsV3L1nDGoFjxoNUnPQQ

Can a digitally native dollar outcompete the systems that built global finance?Sean Neville,  former Co-CEO and President of Circle, unpacks why stablecoins are not just a side note in crypto, they’re the financial infrastructure quietly reshaping global payments, remittances, and even central bank strategy.Together, Sean and Amanda explore how stablecoins are reshaping global finance, from reducing friction in traditional payment systems to creating programmable money with transparency and trust at the core. They dissect the promise of decentralization, the role of regulatory frameworks like the Genius Act, and how Circle’s long-term compliance strategy sets it apart from competitors like Tether. But the conversation doesn’t stop at crypto. Amanda and Sean dive deep into how AI-native institutions are already emerging, why AI agents may soon become primary economic actors, and what the financial world could look like when reliability matters more than cost. Today, Sean is Co-Founder and CEO of Catena Labs.TIMESTAMPS: 00:00 Understanding Stablecoins08:04 Infrastructure and Governance in Stablecoins13:24 The Evolution of Payment Systems16:33 Regulatory Clarity and the Genius Act21:20 Market Dynamics: Circle vs. Tether25:42 The Rise of Stablecoins29:39 AI Native Financial Institutions34:34 The Future of AI in Finance45:59 Navigating the AI Spectrum: Doomers to BloomersRESOURCESSean on X: https://x.com/psnevilleSubscribe to Endgame: https://www.youtube.com/@endgamepodcast  Amanda on X:  https://x.com/amandacassatt  Serotonin on X: https://x.com/serotonin  Endgame on Spotify: https://open.spotify.com/show/6iSvbKOJWoEPiAoGmiulkd   Endgame on Apple Podcasts: https://podcasts.apple.com/us/podcast/endgame-with-amanda-cassatt/id1801809440  Substack: https://substack.com/@UCInZsV3L1nDGoFjxoNUnPQQ

Do you think UBI is inevitable in an AI-driven world?Martin Köppelmann, co-founder of Gnosis, Gnosis Safe, and Circles, believes Universal Basic Income isn’t just possible, it’s inevitable. In a world where AI disrupts the job market, he says we won’t be able to rely on states or billionaires to deliver it.In this episode, Martin and Amanda unpack what “basic” income should really mean. He argues UBI should be simple, universal, and free from government control, biometric scans, or eligibility checks and believes crypto offers a way for communities to create and distribute money themselves without needing permission from centralized powers.Known for building trusted infrastructure in crypto, Martin has spent the last decade quietly obsessed with another question: how do we fund human dignity from the ground up? This is a conversation about post-AI economics, the limits of state welfare, and why issuing your own money might be the most radical and necessary act of all.TIMESTAMPS: 00:00 The Future of Universal Basic Income (UBI)05:33 AI's Impact on Job Markets and UBI09:06 The Mechanics of UBI Implementation12:02 Defining Basic Needs for UBI15:33 Funding UBI: Who Pays?18:49 Preventing Inflation and Maintaining Purchasing Power20:20 Managing Scope Creep in UBI Programs23:13 Dependence on UBI and Societal Resilience25:44 Crypto and UBI: A New Economic Model30:40 Circles: A Community-Based Currency System32:57 The Currency Debate: Martin Tokens vs US Dollar38:00 Circles: A New Approach to Currency42:35 WorldCoin vs Circles: A Comparison of UBI Approaches46:54 Decentralized UBI: Empowering Individuals48:22 Circles 2.0: New Features and Future Prospects54:43 AI Doomsday: The Future of Humanity and AIRESOURCESMartin on X: https://x.com/koeppelmann @koeppelmannSubscribe to Endgame: https://www.youtube.com/@endgamepodcast  Amanda on X:  https://x.com/amandacassatt  Serotonin on X: https://x.com/serotonin  Endgame on Spotify: https://open.spotify.com/show/6iSvbKOJWoEPiAoGmiulkd   Endgame on Apple Podcasts: https://podcasts.apple.com/us/podcast/endgame-with-amanda-cassatt/id1801809440  Substack: https://substack.com/@UCInZsV3L1nDGoFjxoNUnPQQ

Could quantum computers destroy Bitcoin?John Lilic, early Ethereum adopter and crypto investor and Stefano Gogioso, quantum computing expert and Oxford lecturer, unpack one of the biggest threats on crypto’s horizon: Q-Day - the moment quantum computers become powerful enough to break the encryption behind Bitcoin, Ethereum, and the entire blockchain ecosystem.Together with Amanda, they dive deep into what quantum cryptography actually means, why current encryption standards are dangerously outdated, and what crypto needs to do right now to prepare for a post-quantum world. John and Stefano debate how close Q-Day really is, what’s being done (or not) to prevent chaos in the stablecoin and DeFi systems, and why this topic isn’t getting the attention it deserves.TIMESTAMPS00:00 The Threat of Quantum Cryptography05:03 Understanding Quantum Computing and Its Implications10:04 The Race for Quantum Computing Technology14:55 Use Cases and Applications of Quantum Computing19:48 The Preparedness of Blockchain for Quantum Threats28:32 The Quantum Threat to Cryptography31:41 Market Perceptions and Quantum Computing34:55 Valuations in Quantum Computing35:43 Understanding Quantum Progress and Its Implications39:08 The Future of Quantum Cryptography41:38 Innovations in Quantum Cryptography48:12 Preparing for Quantum Risks51:41 Philosophical Implications of Quantum MechanicsRESOURCESJohn & Stefano on X: @LilicJohn & @StefanoGogiosoSubscribe to Endgame: https://www.youtube.com/@endgamepodcast Amanda on X:  https://x.com/amandacassatt  Serotonin on X: https://x.com/serotonin  Endgame on Spotify: https://open.spotify.com/show/6iSvbKOJWoEPiAoGmiulkd   Endgame on Apple Podcasts: https://podcasts.apple.com/us/podcast/endgame-with-amanda-cassatt/id1801809440  Substack: https://substack.com/@UCInZsV3L1nDGoFjxoNUnPQQ