PodcastsScienceFrom First Principles

From First Principles

Krishna Choudhary and Lester Nare
From First Principles
Latest episode

49 episodes

  • From First Principles

    Artemis II, Claude Code Leak, iPhone Spyware & Project Hail Mary (EP 36)

    2026/04/03 | 1h 1 mins.
    Hosted by Lester Nare and Krishna Choudhary, this rundown episode covers five new science and tech stories at a high level: NASA’s Artemis 2 moon mission, what actually leaked in the Claude Code incident, a new cancer genomics paper suggesting domesticated cats may be unusually useful real-world models for human cancer, two leaked iPhone spyware toolkits, and a science-focused review of Project Hail Mary.

    Summary

    Artemis 2 is finally flying — why this mission matters, why it is not landing yet, and why the moon race is back in geopolitical focus.

    Claude Code leaked, but not Claude itself — what was exposed, why people got confused, and why the distinction between source code and model weights matters.

    Cats and cancer — why domesticated cats may offer a more realistic environmental cancer model than traditional lab rodents.

    iPhone spyware in the wild — what Dark Sword and Coruna are, what they can do, and why this signals a broader shift in cyber risk.

    Project Hail Mary science review — what the film gets right, what it gets wrong, and which scientific liberties are hardest to buy.

    Support the show
    Donate: FFPod.com/donate
    Follow: @FFPod on X / Instagram / TikTok / Facebook
  • From First Principles

    Can AI Help Wake Coma Patients? The Science of Consciousness (EP 35)

    2026/03/31 | 1h 8 mins.
    Hosted by Lester Nare and Krishna Choudhary, this episode is a deep dive into one of the hardest questions in neuroscience: what breaks in the brain during a coma, and can we figure out how to turn consciousness back on? We unpack a new paper from Daniel Toker et al. that uses an interpretable AI framework — not a generic black box chatbot model — to reverse engineer the biological mechanisms of prolonged unconsciousness, recover known features of coma, predict new ones, and propose a possible new target for deep brain stimulation.

    Summary

    Why diagnosis is so hard — disorders of consciousness are not just about whether a patient is awake, but whether awareness is still present even when motor output is gone.

    The mesocircuit hypothesis — the episode explains how the cortex, thalamus, and basal ganglia may work together like an electrical grid to support consciousness.

    Interpretable AI, not black-box hype — Daniel Toker’s team built a biophysically grounded model that rediscovered known coma features and predicted two new biological mechanisms.

    A possible stimulation target — the subthalamic nucleus emerged as a standout candidate for deep brain stimulation, suggesting a new path toward restoring wakefulness.

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    Donate: FFPod.com/donate
    Follow: @FFPod on X / Instagram / TikTok / Facebook

    Show Notes
    Daniel Toker et al. — Adversarial AI reveals mechanisms and treatments for disorders of consciousness

    Nicholas Schiff et al. — deep brain stimulation in a minimally conscious patient

    Adrian Owen et al. — fMRI evidence of covert awareness in a patient diagnosed as vegetative
  • From First Principles

    AI Cancer Vaccines, Strange Fish, Ketamine, and Ancient Life (EP. 34)

    2026/03/27 | 44 mins.
    Hosted by Lester Nare and Krishna Choudhary, this episode is a fast-moving science rundown covering four remarkable stories from across AI, genetics, neuroscience, and paleontology. We dig into the story of a machine learning engineer who used AI tools to help design a personalized cancer vaccine for his dog, explore how an all-female fish species has survived far longer than evolutionary theory would predict, unpack new brain-scan evidence for how ketamine may rapidly relieve severe depression, and look at new research suggesting life rebounded shockingly fast after the asteroid that killed the dinosaurs.

    Summary

    AI and personalized medicine — a striking case study in how AI tools may help accelerate highly customized treatments, starting with a rescue dog named Rosie.

    Evolution gets weird — the Amazon molly fish appears to challenge the usual assumptions about why asexual reproduction should fail over long time scales.

    Why ketamine works so fast — new PET imaging research points to brain-region-specific changes in AMPA receptors in treatment-resistant depression.

    Life after catastrophe — microscopic plankton may have evolved into new species within just a few thousand years after the Chicxulub impact.

    Support the showDonate: FFPod.com/donateFollow: @FFPod on X / Instagram / TikTok / Facebook

    Show Notes
    AI-designed dog cancer vaccine story
    https://finance.yahoo.com/news/mans-dog-riddled-tumors-dying-210500037.html?guccounter=1

    Amazon molly / gene conversion paper
    https://www.nature.com/articles/s41586-026-10180-9

    Ketamine / AMPA receptor PET imaging paper
    https://www.nature.com/articles/s41380-026-03510-w

    Post-asteroid plankton recovery paper
    https://www.yokohama-cu.ac.jp/english/news/20260306takahashi.html
  • From First Principles

    Can Human Neurons Really Play Doom? The Science Behind Wetware (EP. 33)

    2026/03/24 | 1h 13 mins.
    Hosted by Lester Nare and Krishna Choudhary, this episode is a deep dive into one of the strangest science stories of the year: a dish of human neurons allegedly learning to play Doom. We go back to the original 2022 DishBrain paper out of Cortical Labs, unpack how biological neurons can be read and written with multi-electrode arrays, and then compare the peer-reviewed Pong result to the much newer Doom claim. The result is a story that is both genuinely impressive and, in places, probably overhyped.

    Summary

    Wetware engineering — replacing artificial neurons with real biological neurons plus electronics, and why some people think this could become a new computing paradigm.

    How DishBrain worked — human stem-cell-derived cortical neurons grown on a multi-electrode array, trained through sensory encoding and a “minimize surprise” feedback loop.

    Where the Doom story gets messy — the newer system appears to include a reinforcement-learning layer in the loop, raising the key question: are the neurons actually doing the learning?

    The big idea underneath the hype — even if Doom is overstated, the broader platform is still a remarkable step toward programmable biocomputing.

    Support the showDonate: FFPod.com/donateFollow: @FFPod on X / Instagram / TikTok / Facebook
  • From First Principles

    5,000-Year-Old Bacteria, Solar Storms, Dogs, and Meta’s AI War (EP. 32)

    2026/03/20 | 38 mins.
    Hosted by Lester Nare and Krishna Choudhary, this is our first standalone rundown episode — a faster, looser format where we hit several stories we didn’t have room to turn into full deep dives. This week: bacteria revived from a Romanian ice cave after 5,000 years, a speculative but fascinating theory linking solar storms to earthquakes, new evidence that dogs and humans share genetic roots for personality traits, and the increasingly dramatic fight over the future of AI after Yann LeCun leaves Meta to build a new billion-dollar company focused on world models.

    Summary
    Ancient bacteria, modern resistance — a microbe revived from a 5,000-year-old Romanian ice cave resists modern antibiotics and may even contain compounds useful against present-day superbugs.
    Solar storms and earthquakes? — a Kyoto University theoretical paper suggests space weather could perturb electric fields in Earth’s crust enough to influence faults already near critical stress.
    Dogs and humans, genetically — a Cambridge / Morris Animal Foundation study finds shared gene pathways that map to personality-like traits in both golden retrievers and humans.
    The Meta AI split — Yann LeCun leaves Meta to pursue AI systems that model the physical world, arguing that simple scaling of LLMs may never reach real general intelligence.

    Support the showDonate: FFPod.com/donateFollow: @FFPod (X / Instagram / TikTok / Facebook)

    Show Notes
    Story 1 — Ancient bacteria in Romanian ice cave (Frontiers in Microbiology)
    Story 2 — Solar storms and earthquakes (Kyoto University / International Journal of Plasma Environmental Science and Technology)
    Story 4 — Dog and human personality genes (PNAS)
    Story 5 — Yann LeCun leaves Meta / world-model AI (Wired)

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About From First Principles

From First Principles is a fast, funny, and rigorous breakdown of the biggest science stories of the week, hosted by Lester Nare and physicist Krishna Choudhary, PhD. We go past headlines into the actual mechanics: what happened, why it matters, and what everyone’s missing. Expect physics, space, AI, energy, biotech, and the occasional “wait… is that real?” story. If you’re curious, skeptical, and you like learning in public — you’re in the right place.
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