Stay ConnectedFrom 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.
Copyright: © Krishna Choudhary and Lester Nare
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.
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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
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.
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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
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Show Notes
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
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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
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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.
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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
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.
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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
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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.
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00:00 Intro
00:32 Episode setup
02:15 Why is ice slippery?
33:23 Rundown + housekeeping + donate
01:09:11 Choking under pressure (neuroscience)
01:32:32 Climate change & the Winter Olympics + potpourri
01:43:47 Wrap-up + closing
Hosted by Lester Nare and Krishna Choudhary, this episode jumps from plant biochemistry to quantum metrology to cancer evolution. We start with a University of York breakthrough that solves a ~50-year mystery in alkaloid biosynthesis—identifying the “missing” enzyme behind a key asymmetric step plants use to build powerful defensive (and pharmaceutically useful) molecules. Then we go deep on quantum sensing with entangled atomic clouds, showing how correlated measurements can beat the standard quantum limit. Finally, we close with ALFA-K, a new tool that maps local fitness landscapes to predict how aneuploid cancers may evolve under pressure from therapy.
Summary
Show Notes
Hosted by Lester Nare and Krishna Choudhary, this episode is a full-spectrum moonshot: why Artemis II matters, how the mission actually works (SLS, Orion, translunar injection, free-return trajectories), and a first-principles teardown of the most common Apollo “hoax” claims—Van Allen belts, waving flags, shadows, and “why aren’t there stars?”
We also run a quick Rundown of wild science headlines (ancient cave art, elevation-dependent warming, dogs and vocabulary, and peptide bonds in deep space), before coming back to the core question: what it takes to send humans safely around the Moon—again.
Summary
Show Notes
Hosted by Lester Nare and Krishna Choudhary, this episode runs from JWST’s “Little Red Dots” (and what they imply about early supermassive black holes), to a TimeVault method for recording gene expression over time, to 8,000-year-old Halaf pottery that may encode geometric sequences — plus a quick Cloud9 follow-up on the “starless dark-matter halo” debate.
Summary
Show Notes
Hosted by Lester Nare and Krishna Choudhary, this episode runs from the deep math of string theory to the biology of sleep—then out to a starless “ghost cloud” that may be a naked dark-matter halo. We open with a Nature paper showing that physical networks in nature (brains, blood vessels, fungal networks) appear to organize like energy-minimizing surfaces—spitting out the same branching rules you see in soap films and (surprisingly) in the mathematics behind string theory. Then we hit a neuroscience twist: even simple jellyfish need sleep—and the evidence points to sleep as a repair cycle for DNA damage. We close with Cloud9, a newly characterized, starless gas cloud that could be a rare “reionization-limited” RELHIC—potentially exposing a dark matter halo without the glare of stars.
Summary
Show Notes
Hosted by Lester Nare and Krishna Choudhary, this episode jumps from ancient engineering to modern AI and markets. We start with the newly uncovered Pompeii worksite that finally shows how Romans mixed their concrete — and why it “self-heals.” Then we pivot into a Princeton neuroscience idea that the brain builds complex thought like LEGO bricks (compositional neural subspaces). From there, we break down DeepSeek’s “manifold-constrained hyperconnections” as a stability mechanism for scaling deep nets. And we close with econophysics: a Physical Review Letters result arguing the square-root law of market impact is strictly universal across stocks and time.
Summary
Show Notes
Hosted by Lester Nare and Krishna Choudhary, this Season Finale closes out Season 1 with a deep dive into the physics behind fusion’s biggest bottleneck: fast magnetic reconnection. We unpack why classic models predicted reconnection should be slow, why nature (and tokamaks) disagree, and how modern “plasmoid” reconnection helps explain solar flares, plasma instabilities, and the real engineering challenges fusion reactors face. Then we run a full Season 1 recap — our favorite episodes, biggest scientific moments, and the corrections and lessons we’re taking into Season 2.
Summary
Hosted by Lester Nare and Krishna Choudhary, this single-story deep dive tells the full story of how humanity uncovered the structure of DNA — and the human tensions that shaped it. From Mendel’s pea-plant mathematics to Rosalind Franklin’s groundbreaking x-ray crystallography, from Cavendish–King’s College rivalries to the famous Photo 51, this episode follows the scientific and ethical arc behind one of the most important discoveries in modern biology.
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Show Notes
Hosted by Lester Nare and Krishna Choudhary, this episode spans astrophysics, forensic chemistry, and neuroimmunology. We begin with a deep dive into 3I/ATLAS, only the third confirmed interstellar object to ever pass through our solar system — larger and stranger than ‘Oumuamua and Borisov, with new imagery released as NASA reopened operations. Then we break down a true-crime forensic breakthrough from Maynooth University that reveals how to recover fingerprints from fired bullet casings — a technique that could radically accelerate criminal investigations. And we close with a Max Planck Institute discovery identifying a regulatory microglial state in the brain that may finally clarify why Alzheimer’s develops — and how immune dysfunction, not just plaques, drives the disease.
Summary
Show Notes
Hosted by Lester Nare and Krishna Choudhary, this episode dives into three breakthroughs stretching across aerospace engineering, astrobiology, and quantum computing. We start with a Nature Communications paper from Stevens Institute that experimentally validates a 60-year-old hypothesis underpinning hypersonic flight modeling. Then we head 3,000 meters below the Pacific to explore a newly discovered cold, ultra-alkaline biosphere near the Mariana forearc — a finding that reshapes the search for extraterrestrial life. And we close with Princeton’s millisecond-coherent transmon qubit, a materials science triumph pushing the quantum hardware frontier toward real-world quantum advantage.
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Show Notes
Hosted by Lester Nare and Krishna Choudhary, this super-episode spans four wildly different frontiers: bioengineers hijacking bacterial evolution to mass-produce octopus camouflage pigment; orcas developing cultural hunting strategies against great white sharks; the bizarre chemistry behind civet-processed luxury coffee; and a UCLA breakthrough that pushes telescope resolution beyond the classical diffraction limit.
Summary
Show Notes
AI, Eyes, and the Sky — From Synthetic Genomes to Restored Vision and Cosmic Mysteries
Hosted by Lester Nare and Krishna Choudhary, this episode of From First Principles explores three cutting-edge breakthroughs connecting medicine, technology, and astronomy.
Summary
• AI for Oncology, Minus the Privacy Risk: University of Toronto researchers develop OncoGAN—a generative model that creates realistic synthetic cancer genomes to accelerate precision oncology while protecting patient data.
• Restoring Sight: The PRIMA (PRIMAvera) trial in NEJM demonstrates how a wireless sub-retinal photovoltaic implant can restore central vision in people with advanced macular degeneration.
• Revisiting Cosmic Transients: New analyses of Palomar’s POSS-I plates re-examine the “multi-point transients” with fresh alignment statistics and an innovative Earth’s-shadow control test.
Show Notes
• University of Toronto — OncoGAN / Synthetic Cancer Genomes (Cell Genomics)
• NEJM — PRIMA (PRIMAvera) Wireless Sub-Retinal Implant Trial for Geographic Atrophy
• Palomar POSS-I Plates — Multi-Point Transient Analysis (IOP PASP Paper)
• Palomar Alignment vs Earth’s Shadow Control (Nature Scientific Reports 2025)
Hosted by Lester Nare and Krishna Choudhary, this episode tells the story of Nobel laureate Chen Ning Yang and how his ideas on symmetry and gauge theory transformed modern physics.
Summary
• Early Years & Mentorship: From China to Chicago — learning under Fermi and Chandrasekhar.
• Parity Violation: How Yang & Lee overturned the mirror-symmetry assumption and changed physics forever.
• Gauge Symmetry & Yang-Mills Fields: The foundation of the Standard Model of particle physics.
• Legacy & Philosophy: Why Yang saw beauty as nature’s signature and symmetry as its language.
Show Notes
• Nobel Prize in Physics 1957 — Chen Ning Yang & Tsung-Dao Lee
• Original Yang–Mills Paper (1954, Physical Review)
• Madame Wu’s Parity Violation Experiment (1957)
• Biography of Subrahmanyan Chandrasekhar (University of Chicago)
Aloha internet — Lester Nare and Krishna Choudhary return with three extraordinary research stories: portable muon beams, sodium-ion batteries, and the secret to long life.
Summary
• Lawrence Berkeley’s compact muon beam technology and its applications in archaeology, volcanology, and security.
• UC San Diego + U Chicago’s solid-state sodium battery that rivals lithium in power but not in cost.
• Tongji University’s naked mole rat DNA study uncovering a genetic pathway for longer, healthier life.
Show Notes
Portable Muon Beam
Nature News Coverage
Physical Review Accelerators and Beams Paper
Sodium Ion Batteries
Science Daily Coverage
Joule Paper (2025)
Naked Mole Rats & Longevity
BBC Coverage
Science Journal Paper
After a packed week of Nobel Prize coverage, Lester and Krishna look back on how From First Principles began and why they built it as an “ESPN for Science.” They revisit 2025’s Medicine, Physics and Chemistry winners and discuss why fundamental research and immigration policy are core to America’s scientific edge.
Quick note: this week’s episode is in vertical format because of a technical hiccup during recording — back to widescreen next week!
Summary
Show Notes
Hosted by Lester Nare and Krishna Choudhary, this one-episode special brings all three 2025 Nobel Prizes in the sciences into a single listen: Medicine (immune tolerance and FOXP3), Physics (macroscopic quantum tunneling in superconducting circuits), and Chemistry (metal–organic frameworks and “new rooms for chemistry”).
Summary
Show Notes
Hosted by Lester Nare and Krishna Choudhary, this two-story, 2.5-hour special sets the table for Nobel Prize Week with deep dives into two recent Nobel-winning domains—gene editing (CRISPR) and gravitational waves (LIGO)—and how AI is accelerating both. We trace CRISPR from bacterial immunity to Stanford’s new “CRISPR-GPT” lab co-pilot, then pivot to how machine learning upgrades are pushing LIGO past its noise limits to capture new classes of gravitational waves.
Summary
• CRISPR, from bacterial immune memory to RNA-programmable genome editing
• The 2012 Science breakthrough: guide RNAs unlock programmable editing
• The patent saga and the 2020 Nobel Prize in Chemistry
• Stanford’s CRISPR-GPT: an AI “co-pilot” trained on expert lab threads and papers
• Experiment planning, guide design, and safety guardrails for CRISPR-GPT
• Biosecurity and ethical guardrails around AI in biology
• LIGO’s foundations: Einstein’s equations, binary pulsars, and interferometer engineering
• The “noise budget”: seismic, environmental, and quantum limits
• AI-driven denoising and template generation: unlocking earlier inspirals and tougher detections
• Funding, leadership, and the global policy race to keep LIGO competitive
• Big picture: AI as an amplifier of discovery in both medicine and physics
Show Notes
Lester Nare and Krishna Choudhary return for Episode 9 of From First Principles, breaking down the latest breakthroughs across AI, physics, biology, and astronomy. From China’s stunning AI leap with DeepSeek to time crystals you can actually see, hidden viruses in our DNA, and the brightest fast radio burst ever detected—this episode spans the cutting edge of science and its global implications.
Summary
• China’s DeepSeek AI model: geopolitics, open science, and the future of AI competition
• Time crystals at room temperature: from theoretical physics to practical cryptography
• Hidden viruses in our DNA: new structures decoded with potential for cancer & autoimmune therapies
• Brightest fast radio burst: unraveling cosmic mysteries with new telescopes and James Webb
Show Notes
• Nature: China’s DeepSeek AI paper (1)
• Nature: China’s DeepSeek AI paper (2)
• Nature: Time crystals with liquid crystals
NASA just dropped what they’re calling the strongest evidence yet for biosignatures on Mars, so we spun up an emergency pod. We break down what the rover actually found in Jezero Crater, why geochemical “life-adjacent” reactions matter, revisit April’s hyped K2-18b claim from Cambridge, and close with brand-new JWST hints of atmospheres on Earth-sized exoplanets. Hosted by Lester Nare and Krishna Choudhary.
Summary
• NASA’s Mars result — Perseverance, Jezero, Bright Angel Formation, and inorganic proxies for life (iron phosphates/sulfides) plus how instruments like PIXL actually read rocks.
• The April headline on K2-18b (“strongest evidence yet”) and what atmospheric retrieval really does and doesn’t prove.
• Fresh JWST papers hinting at atmospheres on TRAPPIST-1 worlds — why that’s huge and how transit spectroscopy underpins it.
Show Notes
• NASA — Mars Biosignature Claim
• Cambridge — K2-18b Atmosphere Study
• Astrophysical Journal Letters — JWST TRAPPIST-1
• Astrophysical Journal Letters — JWST TRAPPIST-1 Atmosphere Study (Paper 2)
Hosted by Lester Nare and Krishna Choudhary, Episode 7 of From First Principles covers four stories at the frontier of science and technology. This week, we dive into new telescope data on the interstellar visitor 3i Atlas, explore a major longevity study that suggests life expectancy may have plateaued, unpack a breakthrough nickel catalyst that could enable no-sort plastic recycling, and look at Microsoft’s analog AI computer — a potential game-changer for energy efficiency and medical applications.
Summary
• Interstellar comet 3i Atlas imaged by Hubble, JWST, TESS, and ESA orbiters
• Longevity study shows human life expectancy may have plateaued post-1939 births
• Northwestern researchers develop a nickel catalyst for no-sort plastic recycling
• Microsoft unveils an analog optical AI computer with 100x GPU efficiency
Show Notes
Hosted by Lester Nare and Krishna Choudhary, Episode 6 of From First Principles covers four groundbreaking stories in science—from rare cosmic explosions to synthetic biology breakthroughs that could save our food supply. This week, we dive into a never-before-seen type of supernova, explore a surprising alliance of viruses and bacteria against cancer, unpack how scientists are turning electron spin into power, and highlight Oxford’s CRISPR-based superfood for honeybees.
Summary
Show Notes
This week we break down four big stories—no PhD required.
Reading “inner speech”: Invasive brain–computer interfaces record neurons in motor cortex and decode attempted vs. inner speech into words. Results from Stanford even generalize to simple symbols and numbers. Cool science, huge privacy questions, and a proposed “brain password” to keep users in control.
What makes us human: UC San Diego highlights human accelerated regions (HARs)—genomic control switches (promoters/enhancers) that tune when and where genes are used. We revisit classic HAR examples and a new result connecting a specific HAR to brain development.
Diamonds get an upgrade: Scientists at HPSTAR (Beijing) grow stronger lab diamonds with clear industrial upside—from cutting tools to power electronics—and potential to reduce harmful mining incentives.
International Year of Quantum (2025): A fast retrospective on 100 years of quantum mechanics and how today’s quantum tech is reshaping computing, sensing, and materials.
Hosts: Lester Nare & Dr. Krishna Choudhary
Show: From First Principles Podcast
Interstellar visitor #3 is here. We unpack 3I ATLAS (why it’s moving so fast, why we finally saw a tail, and how Hubble/JWST—and maybe even Juno—could nail down its makeup). Then we dive into the Vera Rubin Observatory, the 32-gigapixel camera that will turn the entire sky into a time-lapse movie and supercharge discovery. Next: AI just boosted CRISPR by predicting and guiding DNA repair (Pythia), making edits cleaner—especially in non-dividing neurons. And we close with a crossover of dinos + particle physics: preserved T. rex blood vessels revealed by a synchrotron. Mystery Box: the viral “Black aliens” meme.
We go from the universe’s first chemistry to tomorrow’s designer biology, swing by Mars to tune Europa Clipper’s ice radar, and finish with a fresh take on the double-slit experiment.
In this episode
The “oldest molecule” puzzle (HeH⁺), cooling the early universe, and why JWST’s findings matter
Programmable proteins: reassigning codons, recoding organisms, and real biosafety
Europa Clipper’s REASON radar test at Mars: frequencies, ice thickness & ocean clues
Double-slit, demystified: single photons, “which-path” info, and measurement reality
Chapters
00:00 Intro
• 01:26 First molecule
• 22:27 Programmable proteins
• 43:05 Europa radar
• 55:00 Double-slit
• 1:15:03 Sign-off
Lester and Dr. Krishna dive into:
• Beetlejuice & “Bracelet” – why a red super-giant may soon swallow its tiny partner
• Atomic Harlem Shake – 0.15 Å resolution images of thermal jiggles in 2-D materials
• Too Fast, Too Furious – IceCube’s constraints on proton fractions in 10²⁰ eV cosmic rays
• Interstellar Google Maps – New Horizons proves star-pattern navigation works
• Mind-Body Woo-Woo – VR coughs that literally raise your white-blood-cell count
Last week the Earth finished a full rotation one millisecond early – but that’s just the opener.
In this week’s From First Principles we dive into six mind-bending headlines with our trademark mix of hard science and light-hearted banter:
Earth’s fastest spin ever recorded – what shaved a millisecond off the day and why your chakras are still safe.
ALMA spots a “baby Earth” forming 1,300 light years away – the first direct look at rocky planets in the making.
Biggest black-hole merger on record – 15 ☉ of mass vaporized into pure gravitational waves, detected by LIGO/Virgo/KAGRA.
CRISPR reveals a vitamin-D “kill switch” for tumors – how silencing one gene in pancreatic & colon cancers triggers 4,000 downstream changes.
A star that died… then died again – the first confirmed “double-detonation” white-dwarf supernova.
DeepMind’s Aeneas AI deciphers broken Latin tablets – giving historians new text, provenance and dating in seconds.
👋 Hosts • Lester Nare – storyteller & professional curiosity machine • Dr. Krishna Choudhary – Princeton-trained physicist & cosmic tour guide
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