From First Principles

Can sound destroy a tumor without an incision? Dr. Zhen Xu joins Krishna Choudhary to explain histotripsy: focused ultrasound that creates tiny bubbles to mechanically break apart tissue, without relying on heat. From a noise complaint in a University of Michigan lab to the Edison system, Xu traces the unexpected discovery, the physics of cavitation, and the decades of research behind noninvasive liver-tumor treatment. We explore surprising immune effects in animal studies, the #HOPE4LIVER clinical trials, and what remains to be tested for other organs. Recorded in Washington, D.C., on September 28, 2026, before the Golden Goose Awards ceremony. Xu is a histotripsy co-inventor, HistoSonics co-founder, and U-M's Li Ka Shing Professor of Biomedical Engineering. This is the first interview in our Golden Goose series. CHAPTERS 00:00 The discovery that became histotripsy 00:50 A PhD student and a heart problem 03:42 Heat vs. sound: how histotripsy works 07:06 Gas pockets, and why not the lungs 09:06 The first paper (2004) 09:38 "Don't read any papers": Yellow Pages and pig hearts 12:29 Too loud: rethinking the ultrasound pulse 14:56 "Almost like smoke": the 2002 discovery 18:14 Building the equipment, and the Edison system 22:19 Through the skull, and controlling the bubbles 23:50 The physics: pressure waves, bubbles and cells 28:47 Ten years to understand it 32:42 Surgery keeps getting smaller: from ether to Star Trek 35:58 The surprise: an immune response 38:16 Why liver cancer, and 9 of 11 rats 47:19 #HOPE4LIVER: the clinical trial 49:59 How a treatment works 52:27 Recovery and the 20-mile-run anecdote 56:24 The future: worldwide, kidney, pancreas and brain 1:01:33 The Golden Goose Award and federal funding 1:04:31 Sign-off 1:04:41 Outro RESEARCH & FURTHER READING First tissue-erosion paper (2004): https://doi.org/10.1109/tuffc.2004.1308731 High-speed imaging of bubble clouds (2007): https://doi.org/10.1109/tuffc.2007.504 Microtripsy and precise cavitation (2014): https://doi.org/10.1109/tuffc.2014.6722611 Bubble-cloud and cancer-cell interactions (2016): https://doi.org/10.1016/j.ultrasmedbio.2016.05.018 Histotripsy through the skull (2016): https://doi.org/10.1109/tuffc.2016.2531504 Abscopal immune responses: animal research (2020): https://doi.org/10.1136/jitc-2019-000200 Partial treatment of rat liver tumors (2022): https://doi.org/10.3390/cancers14071612 #HOPE4LIVER pivotal trial (2024): https://doi.org/10.1148/radiol.233051 #HOPE4LIVER one-year follow-up (2025): https://doi.org/10.1097/sla.0000000000006720 FDA Edison De Novo review: https://www.accessdata.fda.gov/cdrh_docs/reviews/DEN220087.pdf EDITORIAL NOTES 08:40 / 48:12: Edison received FDA De Novo authorization in 2023 for noninvasive liver-tumor destruction. This is not a general cancer-cure approval. 35:58-47:19: The cited immune-response and 9-of-11 results are animal studies, not human cure rates. 49:17: The one-year trial reported 63.4% local control on primary review and 90% on post hoc review. Technical success and durable tumor control are different measures. 53:46: The 20-mile run is an individual anecdote, not recovery advice; Dr. Xu explicitly advises against it. 55:39: The one-year #HOPE4LIVER update was published in 2025. Clinical and company updates reflect the September 2026 recording. Dr. Xu co-founded HistoSonics. WATCH & LISTEN Episode notes and research: https://ffppod.com/episodes/ep66 Golden Goose science rundown (EP59): https://ffppod.com/episodes/ep59 Watch and listen: https://ffppod.com Subscribe: https://www.youtube.com/@FromFirstPrinciplesPod?sub_confirmation=1 Support the show: https://ffppod.com/donate Follow @FFPPod on Instagram, TikTok, X and Facebook. Breaking down science news so it makes sense to curious people everywhere. #Histotripsy #GoldenGooseAward #SciencePodcast

What happens when AI moves beyond the chatbot and into the laboratory? From Claude-designed proteins that bind scorpion toxins to robots that assemble optics experiments, we examine what AI can do for science and what still has to be proven in the real world. Lester Nare and Krishna Choudhary explore the gap between generating a promising design and demonstrating that it works. We also unpack BrainChat, a research platform that lets epilepsy patients interact with their brain-recording data and contribute feedback to seizure detection, and a 15-year study of orangutan mothers facilitating playdates for their young. Along the way: why binding a toxin is not the same as neutralizing it, how patient feedback can help personalize models, and what cloud laboratories and automated experiments could mean for scientific discovery. Which part of science do you think AI will change most? CHAPTERS 00:00 Playdates, brain data and robot labs 00:29 Hello Internet and Signal Award celebration 02:40 Orangutan mothers and infant playdates 15:18 What 15 years of orangutan observations reveal 25:16 Testing the playdate hypothesis 39:30 BrainChat and patient-guided learning 44:57 Putting patients in the feedback loop 1:02:00 Personalizing seizure detection 1:05:33 What the BrainChat study does not yet establish 1:07:59 Anthropic scorpion-toxin binders 1:15:49 Why a toxin binder is not an antivenom 1:18:31 Fast AI designs, slower laboratory testing 1:19:40 Connecting AI to the physical lab 1:23:22 Robotic optics and automated laboratories 1:28:04 Cloud laboratories and remote experiments 1:33:00 Closing the loop with Lila Sciences 1:37:48 Wrap-up RESEARCH & FURTHER READING Orangutan maternal ranging and infant social play (PNAS): https://pubmed.ncbi.nlm.nih.gov/42837467/ BrainChat and human-AI collaboration in epilepsy (Nature Medicine): https://www.nature.com/articles/s41591-026-04680-4 Claude-designed scorpion-toxin binders (Anthropic): https://www.anthropic.com/research/claude-scorpion-toxin-binder-design Robotic optics experiments (MIT News): EDITORIAL NOTES The orangutan findings are observational evidence of mothers facilitating social play, not direct proof of conscious intent. BrainChat was a small feasibility study, not proof of improved clinical outcomes. The scorpion-toxin work demonstrated binding, not a validated antivenom. On-screen clarifications: 15:20 The first author is Odd T. Jacobson. Maria A. van Noordwijk is a coauthor. 16:06 About 32,600 observation hours were collected over 15 years. That is roughly 3.7 years of continuous observation. 40:39 In epilepsy, deep brain stimulation reduces seizure frequency. Tremor is the Parkinson's disease example here. 47:07 The study included 13 participants: 11 with scalp EEG and 2 with intracranial EEG. 51:01 and 51:35 GPT-4o-mini ran in Penn's HIPAA-compliant Azure OpenAI cloud environment, not locally. 1:18:03 This was an Anthropic announcement, in collaboration with Citrini Research. WATCH & LISTEN Episode notes and research: https://ffppod.com/episodes/ep65 Watch and listen: https://ffppod.com Apple Podcasts: https://podcasts.apple.com/us/podcast/id1830375095 Subscribe: https://www.youtube.com/@FromFirstPrinciplesPod?sub_confirmation=1 Support the show: https://ffppod.com/donate Contact: https://ffppod.com/contact Follow @FFPPod on Instagram, TikTok, X and Facebook.

Can light restore aspects of sight? Can recalling a cold experience change an animal's metabolism? And what can ghost particles and mirror-image molecules tell us about the universe? Lester Nare and Krishna Choudhary follow up on our 2026 Nobel Prize episodes with research building on optogenetics, IceCube and molecular handedness. We unpack an early human vision-restoration trial, cold-memory experiments in mice, cosmic neutrino flavors, and a tiny electrical sensor for distinguishing left- and right-handed amino acids. Plus: how the Nobels work, our follow-up on the Nobel chemistry illustration, a brief look at neutrino Earth tomography, and why fundamental research matters. Which discovery would you like us to explore next? CHAPTERS 00:00 Cold open: memory, neutrinos and mirror molecules 00:28 Hello Internet and how the Nobels work 04:32 Optogenetics recap 10:23 Restoring aspects of vision 25:43 Controlling movement in worms 29:31 Cold memories and metabolism 41:07 Memory, trauma and ethical questions 45:44 FFP housekeeping 48:17 IceCube recap 56:23 Measuring cosmic neutrino flavors 1:10:30 A brief look at neutrino Earth tomography 1:12:20 Why fundamental physics matters 1:26:58 Chemistry and molecular handedness 1:29:08 Correcting the Nobel illustration 1:39:30 Measuring chirality in tiny samples 1:46:42 Testing the sensor on meteorite and desert samples 1:51:22 Why these questions matter 1:57:20 Closing thoughts and signoff RESEARCH & FURTHER READING Optogenetic therapy for visual function (NEJM, 2026): https://doi.org/10.1056/NEJMoa2602215 Cold memories and thermoregulation (Nature, 2025): https://doi.org/10.1038/s41586-025-08902-6 Three-flavor composition of cosmic neutrinos (PRL, 2026): https://doi.org/10.1103/vntd-m133 Chiral discrimination in meteorite and desert soil extracts (Nature Communications, 2026): https://doi.org/10.1038/s41467-026-77947-6 Further reading, briefly mentioned: neutrino Earth tomography (preprint): https://arxiv.org/abs/2607.02644 EDITORIAL NOTES The vision trial was small and exploratory. The cold-memory findings discussed are from mice. On-screen clarifications: 16:53 Both eyes were profoundly visually impaired; the worse-seeing eye was treated. 19:57 The untreated eye was patched during testing, not a normal-vision control. 54:41 Neutrino event rates depend on energy and selection, not just detector volume. 1:05:47 Flavor identification efficiency is distinct from interaction probability; both depend on energy. 1:13:35 Other astronomy-related Nobels include 2017 (LIGO) and 2019 (cosmology/exoplanets). 1:18:00 The LHC at CERN enabled the Higgs discovery; CERN itself was founded in 1954. 1:44:25 Both enantiomers produce current signals; waveform features distinguish them. 1:46:42 Murchison is a meteorite. Diego de Almagro and North of Antofagasta are soil sites. 1:47:40 The sensor study reports mixed agreement and limitations, not uniformly negative results. 1:49:00 Phobos is a Martian moon; a captured-asteroid origin is a hypothesis. WATCH & LISTEN Full video: https://youtu.be/C9K6onZxyN4 Episode notes: https://ffppod.com/episodes/ep64 Follow @FFPPod on Instagram, TikTok, X and Facebook. Breaking down science news so it makes sense to curious people everywhere.

Why does life favor one molecular mirror image? The 2026 Nobel Prize in Chemistry honors Henri B. Kagan and Kenso Soai for nonlinear effects and autocatalysis in asymmetric organic synthesis. Lester Nare and Krishna Choudhary unpack the science from first principles: chirality, Pasteur's crystals, enantiomeric excess, and how a tiny imbalance can grow into an overwhelming preference for one molecular hand. We connect Kagan's catalyst discoveries and the Soai reaction to medicines, the origins of biological handedness, and the serious concerns around hypothetical mirror life. Plus: symmetry in physics, Frances Oldham Kelsey and thalidomide, and our interpretation of a Nobel illustration. CHAPTERS 00:00 Why life has a molecular handedness 01:33 Hello Internet 02:49 The 2026 Chemistry laureates 06:24 Chirality and mirror-image molecules 12:10 Pasteur and the history of handedness 19:36 Why is life's chemistry one-handed? 24:35 Frank and the origin-of-life puzzle 29:14 Enantiomeric excess explained 30:30 Kagan and nonlinear effects 38:58 FFP and symmetry in physics 42:20 Soai and asymmetric autocatalysis 51:28 Why chirality matters for medicine 58:21 What this does and does not explain about life 1:00:25 Mirror life and biological risk 1:10:37 Examining the Nobel illustration 1:14:10 Recap and Nobel week reflections RESEARCH & FURTHER READING Original papers and supporting context: Frank's model (1953): https://doi.org/10.1016/0006-3002(53)90082-1 Puchot, Kagan et al. (1986): https://doi.org/10.1021/ja00269a036 Soai et al. (1995): https://doi.org/10.1038/378767a0 Sato et al., amplification (2003): https://doi.org/10.1002/anie.200390105 Mirror-life risks (2024): https://doi.org/10.1126/science.ads9158 Nobel announcement: https://www.nobelprize.org/prizes/chemistry/2026/press-release/ EDITORIAL NOTES Intro: the 50:50 example describes an unbiased synthesis, not all chemistry. The Soai reaction is a clue to amplification, not proof of how life began. On-screen clarifications: 04:38 B-DNA is right-handed; Z-DNA can form a left-handed helix. 13:56 Pasteur separated sodium ammonium tartrate crystals. 18:48 L/D configuration does not specify optical rotation. 19:10 Proteins mainly use L-amino acids; DNA/RNA use D-sugars. 22:55 Mentos mainly triggers CO2 bubble nucleation. 27:18 Asymmetric catalysis and autocatalysis are distinct. 34:07 0.25 × 0.25 = 0.0625 = 6.25%. 36:31 Inactive mixed catalyst pairs are a simplified model. 37:55 The normalized product-ratio curve need not be parabolic. 42:04 Wu: preferential emission opposite spin; antineutrinos also emitted. 45:30 5-pyrimidyl alkanol; an alkanol is an alcohol. 47:10 The tiny-imbalance result is Sato et al. (2003), cited above. 47:40 A demonstration of symmetry breaking by asymmetric autocatalysis. 49:09 Above 99.5% ee means above 99.75% majority form, not exactly 100%. 49:57 0.00005% excess is 1 part in 2,000,000. 52:44 Thalidomide enantiomers interconvert in the body. 53:36 Merrell applied in the U.S.; Kelsey withheld approval. Trial exposure occurred. 1:02:09 Mirror-life catastrophe is a serious risk, not an observed outcome. 1:03:28 Antibodies are adaptive immunity, not innate immunity. 1:03:53 Impaired recognition does not mean proven total immune invisibility. 1:04:27 Some treatments might work; ecosystem protection is very difficult. 1:04:56 No reproducing mirror organism has been reported. 1:09:19 Chimeras and genetic modification are not interchangeable. 1:10:37 The Nobel-diagram critique is our interpretation, not an official correction. 1:11:51 Solid wedge: toward; hashed wedge: away; ordinary line: neither. WATCH & FOLLOW Full video: https://youtu.be/Wdapv1hFT4w Episode notes: https://ffppod.com/episodes/ep63 Follow @FFPPod on Instagram, TikTok, X and Facebook. Breaking down science news so it makes sense to curious people everywhere.

Why build a telescope inside a billion tons of Antarctic ice? The 2026 Nobel Prize in Physics recognizes Francis Halzen's work on IceCube and the discovery of high-energy neutrinos from the cosmos. In Episode 62 of From First Principles, Lester Nare and Krishna Choudhary explain neutrinos from the ground up: why these elusive particles make powerful cosmic messengers, how faint flashes of Cherenkov light reveal their interactions, and why detecting them requires an observatory buried deep beneath the South Pole. We follow the path from beta decay and the first neutrino experiments to AMANDA, IceCube's construction, the 2013 astrophysical breakthrough, a distant blazar, and a neutrino map of the Milky Way. Along the way: cosmic rays, the Oh-My-God particle, tracks versus cascades, and the international collaboration behind the discovery. CHAPTERS 00:00 Hunting ghost particles beneath Antarctica 01:16 Hello Internet and Nobel Prize 05:30 What are neutrinos? 10:00 Neutrinos as cosmic messengers 15:02 The Oh-My-God particle 16:21 Cosmic-ray energies 19:07 Cosmic particle accelerators 22:28 Why look for neutrinos? 25:52 How to detect a neutrino 29:23 Cherenkov light 33:13 Building a neutrino observatory 37:17 From Antarctic ice to AMANDA 42:21 Building IceCube 44:59 Reading tracks and cascades 49:30 Backgrounds and the 2013 discovery 52:46 Tracing cosmic neutrino sources 54:16 Mapping the Milky Way 58:23 IceCube collaboration and Gen2 1:01:05 Closing and Nobel week RESEARCH & FURTHER READING AMANDA in Antarctic ice (2001): https://doi.org/10.1038/35068509 IceCube detector and instrumentation (2017): https://doi.org/10.1088/1748-0221/12/03/P03012 First PeV neutrinos (2013): https://doi.org/10.1103/PhysRevLett.111.021103 Astrophysical neutrino evidence (2013): https://doi.org/10.1126/science.1242856 Blazar TXS 0506+056 (2018): https://doi.org/10.1126/science.aat1378 Archival blazar neutrino emission (2018): https://doi.org/10.1126/science.aat2890 Milky Way neutrino map (2023): https://doi.org/10.1126/science.adc9818 Gamma-ray burst constraints (2012): https://doi.org/10.1038/nature11068 IceCube overview: https://icecube.wisc.edu/science/icecube/ EDITORIAL NOTES Intro: the 2013 breakthrough was high-energy astrophysical neutrinos. Lower-energy supernova neutrinos were detected in 1987. On-screen clarifications: 06:45 Beta-minus decay produces a proton, electron and electron antineutrino. 11:10 Davis studied solar neutrinos; Koshiba's team detected SN 1987A neutrinos. 17:50 The cosmic-ray knee and ankle are not fixed distance boundaries. 19:38 Required accelerator size depends on magnetic-field strength. 24:18 Ground-based telescopes also detect gamma rays through air showers. 27:48 W interactions produce charged leptons; Z scattering preserves neutrino flavor. 34:06 The underwater concept dates to 1960; DUMAND developed in the 1970s. 36:09 Baikal holds about one-fifth of unfrozen surface freshwater. 38:53 Earth filters muons but also absorbs many very-high-energy neutrinos. 41:26 Pressure converts air bubbles into clathrates, reducing light scattering. 42:28 Construction finished in December 2010; full operations began in May 2011. 44:27 Sensors are DOMs; DeepCore is a densely instrumented detector region. 45:47 Timing gives direction; light yield and pattern help estimate energy. 49:44 Upgoing events can still be atmospheric neutrinos. 53:12 TXS 0506+056 is about 3.7 billion light-years away. 56:38 Long GRBs often involve collapsing stars; short GRBs often involve mergers. WATCH & FOLLOW Full video: https://youtu.be/eMahxeBj5k0 Episode notes: https://ffppod.com/episodes/ep62 Medicine Nobel explained: https://youtu.be/PKAYqhy8xf8 Follow @FFPPod on Instagram, TikTok, X and Facebook. From First Principles: Breaking down science news so it makes sense to curious people everywhere.

How do you prove what a brain cell actually does? The 2026 Nobel Prize in Medicine celebrates a remarkable answer: give cells a light-sensitive protein, then switch their activity on or off with light. In Episode 61 of From First Principles, Lester Nare and Krishna Choudhary explain optogenetics from the ground up and trace the discoveries of Peter Hegemann, Georg Nagel and Karl Deisseroth. We follow the story from algae swimming toward light to channelrhodopsins, precisely controlled neurons, and experiments probing memory, reward and behavior. Then we explore heart-brain connections, early attempts to restore vision, and what these experiments can and cannot tell us. CHAPTERS 00:00 The discovery that put brain cells under light control 02:34 Hello Internet 03:28 2026 Medicine Nobel and optogenetics 05:38 Understanding the brain 08:42 From correlation to causation 18:13 Controlling neurons with light 21:25 Early optogenetics and the chARGe system 24:17 Light-sensitive microbial proteins 26:26 Algae and phototaxis 31:42 Discovering channelrhodopsins 34:42 Nagel and light-gated ion channels 40:55 Controlling mammalian neurons 50:19 Expanding the optogenetic toolkit 56:10 Neural circuits and behavior 59:02 Memory, reward and reinforcement 1:02:53 Heart rhythm and emotion 1:04:02 Beyond the brain and toward medical treatments 1:06:56 Implications and limits 1:09:10 Closing and Nobel week RESEARCH & FURTHER READING Full paper list: https://ffppod.com/episodes/ep61 Nobel Prize announcement and background: https://www.nobelprize.org/prizes/medicine/2026/summary/ Optical control of neurons: https://doi.org/10.1038/nn1525 Memory recall in mice: https://doi.org/10.1038/nature11028 Partial visual recovery: https://doi.org/10.1038/s41591-021-01351-4 EDITORIAL NOTES On-screen clarifications are included at these timestamps: 13:46 The Jennifer Aniston neuron was recorded in human patients. Selective firing alone did not establish that it causes recognition. 30:34 Vertebrate rhodopsin is a GPCR. In rods and cones, light closes cGMP-gated channels and causes hyperpolarization. 35:12 Xenopus oocytes are immature frog egg cells, not embryos. 39:52 Calcium entry triggers neurotransmitter release; neurotransmitters carry the signal across the synapse. ChR2 conducts several positive ions, not just calcium. 52:17 Halorhodopsin is a light-driven chloride pump, not a channel. 1:03:18 The heart-pacing study expressed ChRmine in mouse heart muscle cells, not neurons. Animal studies and early clinical results are distinguished from established treatments. WATCH & LISTEN Watch this episode: https://youtu.be/PKAYqhy8xf8 Our Nobel predictions: https://open.spotify.com/episode/4xuoH7WhM5svq8vEJPL3Ce Support: https://ffppod.com/donate Contact: https://ffppod.com/contact Follow @FFPPod. Breaking down science news so it makes sense to curious people everywhere.

Who could win the 2026 Nobel Prizes? From the science behind Ozempic to quantum interference and droplets inside living cells, Lester Nare and Krishna Choudhary make their picks for Medicine, Physics and Chemistry, and explain the discoveries behind them. In Episode 60 of From First Principles, we explore seven research areas with a case for Nobel recognition: GLP-1, optogenetics, optical coherence tomography, the Aharonov–Bohm effect, atomic force microscopy, biomolecular condensates and Buchwald–Hartwig coupling. We also discuss Michael Berry’s geometric phase and the awkward question of how a prize limited to three people recognizes discoveries built by larger teams. These are our predictions, recorded before the 2026 announcements. Medicine, Physics and Chemistry will be announced October 5–7. Which discovery, and which researchers, would you pick? Tell us in the comments, then join us for our Nobel week breakdowns. CHAPTERS 00:00 The science that could win a Nobel Prize 00:57 Hello Internet: our 2026 predictions 02:03 Medicine: GLP-1 and the science behind Ozempic 07:41 Medicine: optogenetics and controlling neurons with light 13:16 Medicine: optical coherence tomography 16:28 Golden Goose Awards and FFP updates 18:39 Physics: the Aharonov–Bohm effect and geometric phase 27:37 Physics: atomic force microscopy 32:04 Chemistry: biomolecular condensates 36:36 Chemistry: Buchwald–Hartwig coupling 38:42 Your predictions and our Nobel week plans RESEARCH & FURTHER READING Foundational papers and background for the discoveries discussed: GLP-1: Mojsov, Weir & Habener (1987) https://doi.org/10.1172/JCI112855 Optogenetics: Boyden et al. (2005) https://doi.org/10.1038/nn1525 Optical coherence tomography: Huang et al. (1991) https://doi.org/10.1126/science.1957169 Aharonov–Bohm effect (1959) https://doi.org/10.1103/PhysRev.115.485 Berry’s geometric phase (1984) https://doi.org/10.1098/rspa.1984.0023 Atomic force microscopy: Binnig, Quate & Gerber (1986) https://doi.org/10.1103/PhysRevLett.56.930 Biomolecular condensates: Brangwynne et al. (2009); Li et al. (2012) https://doi.org/10.1126/science.1172046 https://doi.org/10.1038/nature10879 Buchwald–Hartwig coupling: Paul et al. (1994); Guram et al. (1995) https://doi.org/10.1021/ja00092a058 https://doi.org/10.1002/anie.199513481 Official Nobel announcement schedule: https://www.nobelprize.org/prizes/about/prize-announcement-dates/ EDITORIAL NOTES 19:30 David Bohm later held a professorship at Birkbeck, University of London (1961–1987); he did not spend the rest of his career in Brazil. 33:23 The ribosome-producing compartment discussed is the nucleolus, not the nucleosome. These corrections also appear on screen. WATCH & EXPLORE YouTube: https://youtu.be/MgOpbh5VUGE Episode page and research library: https://ffppod.com/episodes/ep60 Support: https://ffppod.com/donate Follow @FFPPod on X / Instagram / TikTok / Facebook Breaking down science news so it makes sense to curious people everywhere.

What connects a noise complaint, holiday lights seen from space, and the physics of a coffee stain? Three unexpected paths from basic research to discoveries with real-world impact. Krishna Choudhary and Lester Nare explore the science behind the 2026 Golden Goose Awards: Zhen Xu's work on histotripsy, NASA's Black Marble nighttime satellite data, and Sidney Nagel's discoveries in soft matter physics. We start with focused ultrasound and the tiny bubbles that can break apart targeted tissue, tracing the journey from early laboratory experiments to clinical research on liver tumors. Then we look at how Earth's nighttime lights reveal power outages, disaster recovery, and changing human activity. Finally, falling drops, coffee stains, and jammed grains open up a world of robotic grippers and materials that can be trained and retrained. The thread connecting all three stories is the unexpected value of federally funded basic research. Part 2 will feature conversations with the award-winning researchers and AAAS CEO Sudip Parikh. CHAPTERS 00:00 Golden Goose Awards trailer 01:19 Introducing our Golden Goose special 02:42 Zhen Xu: From a noise complaint to histotripsy 05:57 The early ultrasound experiments 13:42 Controlling cavitation with microtripsy 20:29 Tumor destruction and the immune response 28:33 Histotripsy through the skull 37:23 The HOPE4LIVER clinical trial 43:55 Why basic research needs time 47:17 FFP updates and supporting the show 49:20 NASA Black Marble: Holiday lights from space 55:29 Turning night lights into reliable data 1:01:36 Hurricane Maria and unequal recovery 1:08:12 COVID-19 and changing nighttime activity 1:10:16 Mapping access to electricity 1:15:20 Where Earth is brightening and dimming 1:32:57 Sidney Nagel and the physics of everyday life 1:37:07 The science of a falling drop 1:46:02 Why coffee leaves a ring 1:51:04 Jamming: When grains become rigid 1:53:35 A robotic gripper filled with grains 1:55:39 Why air pressure changes a splash 1:58:55 Materials that can be trained and retrained 2:03:26 The payoff from curiosity 2:05:29 Coming in Part 2 2:07:06 Outro FEATURED RESEARCH Histotripsy: The #HOPE4LIVER single-arm pivotal trial (Radiology, 2024) https://doi.org/10.1148/radiol.233051 NASA's Black Marble nighttime lights product suite (Remote Sensing of Environment, 2018) https://doi.org/10.1016/j.rse.2018.03.017 Training and retraining liquid crystal elastomer metamaterials for pluripotent functionality (PNAS, 2025) https://doi.org/10.1073/pnas.2504304122 WATCH ON YOUTUBE https://youtu.be/rDInUEtTojg EXPLORE FFP Website: https://ffppod.com Science Funding Tracker: https://ffppod.com/funding Science Transfer Portal: https://ffppod.com/transfers America 250: https://ffppod.com/America250 SUPPORT THE SHOW https://ffppod.com/donate FOLLOW @FFPPod on X / Instagram / TikTok / Facebook

What does it mean to solve an equation that describes almost every fluid around us, from the air over a wing to the water swirling down a drain? In Episode 58 of From First Principles, Lester Nare and Krishna Choudhary build the Navier-Stokes equations from the ground up before digging into OpenAI’s claimed breakthrough and the debate surrounding it. Summary How Newton’s laws become equations for a moving fluid Velocity fields, incompressibility, pressure and the nonlinear convective term Why viscosity smooths a fluid while nonlinear motion can create finer structure What finite-time blowup means, and why simulation is different from proof How forced and unforced equations differ, and why those assumptions matter Earlier work on Euler, Boussinesq and related fluid equations OpenAI’s claimed result, Lean verification and the scope of the theorem The dispute over scientific credit and the human research behind AI-assisted work The METR investigation of the Hugging Face incident Emergence World and long-running multi-agent experiments AI-assisted biological discovery, oversight and recursive self-improvement Separating demonstrated capabilities from claims and future scenarios Chapters 00:00 Can AI solve Navier-Stokes? 00:34 Episode introduction 02:20 Navier-Stokes: Mathematics Meets AI 10:20 Building the Equations of Fluid Motion 21:34 Velocity fields, divergence and incompressibility 34:33 Acceleration and the convective term 52:18 Why Fluid Motion Is Nonlinear 1:02:08 Pressure, Euler and the Missing Physics 1:14:50 How Viscosity Changes Everything 1:33:36 Solving Equations vs. Simulating Fluids 1:44:59 Can a Smooth Fluid Blow Up? 2:13:52 The Road to the Claimed Breakthrough 2:31:13 Inside the Claimed Navier-Stokes Proof 2:48:26 The Dispute Over Scientific Credit 3:07:23 From Chatbots to Agents 3:08:57 The METR report and Hugging Face incident 3:23:23 AI Risk, Oversight and the Race Ahead 3:38:51 AI Discovery Beyond Mathematics 3:52:47 Why “just turn it off” gets complicated 4:06:47 Closing thoughts and what comes next 4:08:46 Outro Featured Research OpenAI’s Navier-Stokes announcement Tristan Buckmaster’s statement METR investigation Emergence World AI-assisted enzyme discovery Explore FFP ffppod.com ffppod.com/funding ffppod.com/transfers ffppod.com/America250 Watch on YouTube youtu.be/NGfGw1tGxUY Support the show ffppod.com/donate Follow @FFPPod on X / Instagram / TikTok / Facebook

What science should you be watching this fall? From Nobel Prize season to NASA’s Roman Space Telescope, Mars’ moons and Mercury, Lester Nare and Krishna Choudhary take a relaxed tour of the discoveries and missions on their radar. In Episode 57 of From First Principles, we explore why curiosity-driven research matters, what the Golden Goose Awards celebrate, and how questions that once sounded impractical can lead to unexpected breakthroughs. Then we turn to space: Roman’s search for dark energy and exoplanets, JAXA’s Martian Moons eXploration (MMX) mission, and the mysteries ESA and JAXA’s BepiColombo mission will investigate at Mercury. Along the way, we tour the updated FFP website, revisit some favorite episodes, and ask which stories you want us to cover in depth next. A note before we begin: the main conversation was recorded before Labor Day weekend. The opening announcement addresses your requests for a separate episode on OpenAI, Navier–Stokes and the wider AI conversation. This episode is our fall science rundown; that deep dive is still to come. CHAPTERS 00:00 Update on our upcoming Navier–Stokes and AI coverage 03:43 Episode intro and football banter 05:47 FFP intro 06:01 Nobel Prize season and our coverage plans 10:45 Golden Goose Awards: why basic research matters 21:02 FFP website tour and favorite episodes 42:24 Nancy Grace Roman Space Telescope 46:20 Microlensing, exoplanets and dark matter 51:25 MMX: where did Mars’ moons come from? 54:40 BepiColombo and the mysteries of Mercury 1:02:17 Your questions, future deep dives and sign-off 1:05:40 Outro SHOW NOTES NASA’s Nancy Grace Roman Space Telescope: https://science.nasa.gov/mission/roman-space-telescope/ JAXA’s Martian Moons eXploration (MMX): https://www.mmx.jaxa.jp/en/mission/ ESA / JAXA BepiColombo: https://www.esa.int/Science_Exploration/Space_Science/BepiColombo Explore the research and episodes we cover: https://ffppod.com Science R&D Funding Tracker: https://ffppod.com/funding Science Transfer Board: https://ffppod.com/transfers America 250: https://ffppod.com/America250 Support the show: https://ffppod.com/donate WATCH ON YOUTUBE https://youtu.be/snhQh0fjTX4 Follow @FFPPod on X / Instagram / TikTok / Facebook Breaking down science news so it makes sense to curious people everywhere. Which mission or research story deserves a full FFP deep dive? Tell us in the comments.