From First Principles

Krishna Choudhary and Lester Nare

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.

  1. 1 DAY AGO

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

    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

    1hr 13min

  2. 5 DAYS AGO

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

    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)

    39 min

  3. 18 MAR

    Optovolution: Teaching Proteins to Think Like Computers (EP. 31)

    Hosted by Lester Nare and Krishna Choudhary, this episode is a deep dive into a new synthetic-biology breakthrough out of EPFL: OptoEvolution. The big idea is simple but powerful — traditional directed evolution is great at making proteins that are always “on,” but biology is full of proteins that need to switch states, respond to stimuli, and behave more like logic gates than static tools. This paper takes directed evolution and couples it to light and the cell cycle, creating a new way to evolve dynamic proteins that can toggle, compute, and respond with far more control. Summary Why directed evolution needed an upgrade — classic methods select for proteins with continuous function, not proteins that toggle between active and inactive states.OptoEvolution — using light as a control signal and the cell cycle as a built-in oscillator to evolve proteins that must turn on and off to survive.Color-multiplexed biology — engineering proteins to respond to different wavelengths of light, opening the door to finer control of gene expression.Single-protein logic gates — proof-of-concept AND-gate behavior inside a single protein, hinting at a future where biology can be programmed with much more software-like precision.Support the showDonate: FFPod.com/donateFollow: @FFPod on X / Instagram / TikTok / Facebook Show Notes OptoEvolution / dynamic protein control (Cell)

    56 min

  4. 16 MAR

    Can We Stop an Asteroid? The Physics Behind NASA’s DART Mission (EP. 30)

    Hosted by Lester Nare and Krishna Choudhary, this episode is a full deep dive on planetary defense. We break down NASA’s DART mission, why the goal was never to “blow up” an asteroid but to gently nudge it, and why the newest result is even bigger than the original headline: scientists can now directly detect that the Didymos–Dimorphos system changed not just locally, but in its heliocentric path around the Sun. Summary DART actually worked — not just by shortening Dimorphos’s local orbit around Didymos by 33 minutes, but by measurably changing the motion of the whole binary system around the Sun. Planetary defense is a measurement problem — the new result hinges on detecting a velocity shift of just 11 microns per second in an asteroid system moving tens of kilometers per second. Why ejecta matters — the impact transferred more momentum than the spacecraft carried in, thanks to debris blasting off the asteroid and boosting the total deflection. Why this matters for Earth — for the first time in our planet’s history, life on Earth may actually have the tools to alter its own cosmic fate.Support the show Donate: FFPod.com/donate Follow: @FFPod on X / Instagram / TikTok / Facebook Chapters 00:00 New single-story format 01:53 DART mission setup 18:26 Why the binary asteroid system matters 31:36 Measuring the heliocentric deflection 46:28 Planetary defense implications 53:37 OutroShow Notes DART heliocentric deflection result — Science Advances NASA DART mission overview ESA HERA mission

    54 min

  5. 12 MAR

    Astrobiology’s Biggest Survival Test + A Vaccine Against Everything? (EP. 29)

    Hosted by Lester Nare and Krishna Choudhary, this episode starts in astrobiology with a fresh experimental challenge to one of the biggest objections to lithopanspermia: can life actually survive the violence of being blasted off a planet by an asteroid impact? Then, after a packed Rundown, we pivot hard into immunology with a radical Stanford paper asking whether we could build one nasal vaccine that doesn’t target a specific pathogen at all—but instead makes the lung itself a stronger fortress against whatever shows up. Summary Lithopanspermia gets less crazy — a Johns Hopkins / PNAS Nexus study tests whether extremely resilient microbes can survive the initial shock of ejection from a planet, potentially closing the last major bottleneck in rock-to-rock transfer of life. The universal-vaccine idea — instead of training the adaptive immune system on one pathogen, Stanford asks whether the lung itself can be preconditioned to respond broadly and rapidly to many threats. The Rundown — AI for materials science, orbital nuclear conflict simulations, and other frontier stories the guys wanted to hit even without full deep dives. Support the showDonate: FFPod.com/donateFollow: @FFPod (X / Instagram / TikTok / Facebook) Show Notes Lithopanspermia / impact survival (PNAS Nexus, Johns Hopkins) https://academic.oup.com/pnasnexus/article/5/3/pgag018/8503064 Pathogen-agnostic nasal vaccine (Science, Stanford) https://www.science.org/doi/10.1126/science.aea1260

    2h 4m

  6. 4 MAR

    Dark Galaxies, Fuzzy Dark Matter, and an Alzheimer’s Breakthrough (EP. 28)

    Hosted by Lester Nare and Krishna Choudhary, this episode has two main stories: an astrophysics update on a candidate “dark galaxy” in the Perseus Cluster (a halo that’s ~99.9% dark matter), and a major Alzheimer’s mechanism paper tracing how exercise protects the brain by repairing the blood–brain barrier—with an actionable drug-like path already emerging. Summary Candidate dark galaxy — Hubble + Euclid stacking and globular clusters reveal an ultra-faint halo that could test missing satellites and the cusp–core problem (and even “fuzzy dark matter”). Exercise → Alzheimer’s mechanism — UCSF links a liver enzyme (GPLD1) to BBB repair via TNAP regulation, plus an oral TNAP inhibitor (SBI-425) that mimics the effect in mice. Rundown — Rubin Observatory’s real-time alert engine, AI-accelerated magnet discovery, a climate-corrected Easter Island history, and the Boba-Kiki effect in baby chicks. Support the showDonate: FFPod.com/donateFollow: @FFPod (X / Instagram / TikTok / Facebook)

    1hr 52min

  7. 26 FEB

    Dream Engineering, the Proton Radius Puzzle, and an ALS Breakthrough (EP. 27)

    Hosted by Lester Nare and Krishna Choudhary, this episode has three main stories: interactive dream engineering (yes, two-way “communication” during lucid dreaming), the proton radius puzzle finally getting resolved by a precision lab measurement, and a sobering but hopeful look at ALS—including a breakthrough “ALS-in-a-dish” model that could finally make drug screening translate to humans. Summary Dream engineering — targeted cues + induced lucidity → dream-content biasing and measurable next-day performance gains.Proton radius puzzle — precision hydrogen spectroscopy resolves the decade-long discrepancy; normal hydrogen agrees with muonic hydrogen.ALS — a predictive iPSC motor-neuron model that correlates with patient survival and reveals a promising multi-drug synergy.Rundown — pulsar near the Milky Way center, AI decoding a Roman board game, hormones + evolution signals, and AI-in-the-loop protein engineering.Support the showDonate: FFPod.com/donateFollow: @FFPod (X / Instagram / TikTok / Facebook)

    2h 12m

  8. 18 FEB

    Winter Olympics Deep Dive: Ice Physics, Performance Pressure, and Climate Change (EP. 26)

    Hosted by Lester Nare and Krishna Choudhary, this episode is a Winter Olympics deep dive from first principles—physics, neuroscience, and climate science in one ride. • Why ice is slippery: the “water layer” story is incomplete—new nanoscale measurements suggest a far more viscous, thicker interfacial film than textbook intuition.• Choking under pressure: how high stakes can disrupt neural control—reward signals can push brain states out of the “optimal zone.”• Climate change vs winter sports: why artificial snow has limits, why some legacy venues may become unreliable, and what “snow farming” is trying to solve.• Rundown: AI doing physics proofs, cat vocalizations, immune epigenetics, origin-of-life genetics, and an “impossible” exoplanet system. Support the show: FFPpod.com/donateFollow: @FFPod (X / Instagram / TikTok / Facebook) 00:00 Intro00:32 Episode setup02:15 Why is ice slippery?33:23 Rundown + housekeeping + donate01:09:11 Choking under pressure (neuroscience)01:32:32 Climate change & the Winter Olympics + potpourri01:43:47 Wrap-up + closing

    1hr 50min
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About

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.

Information

  • Creator
    Krishna Choudhary and Lester Nare
  • Years Active
    2025 - 2026
  • Episodes
    33
  • Rating
    Clean
  • Copyright
    © Krishna Choudhary and Lester Nare
  • Show Website
    From First Principles

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