From First Principles

Lester Nare and Krishna Choudhary
  • 5.0 (53)
  • SCIENCE
  • UPDATED WEEKLY

We break down the week’s biggest science headlines from first principles—because understanding the world shouldn’t require a PhD.

  1. 5H AGO

    FFP EP. 16 | Octopus Camouflage, Orcas vs. Sharks, Civet Coffee & Sub-Diffraction Telescope Tech

    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 UCSD’s biosynthesis breakthrough — how researchers engineered a growth-coupled, plug-and-play metabolic pathway to mass-produce xanthomatin, the cephalopod pigment behind octopus camouflage.Orca vs. shark culture wars — first-ever documentation of coordinated predation on juvenile great whites in Mexican waters, plus how whales transmit learned behavior socially.The paradox of civet coffee — wild civet gut chemistry, medium-chain esters, and how microbial fermentation creates the world’s most expensive “biologically processed” coffee.UCLA’s telescope hack — a mode-sorting instrument that extracts phase information from starlight, enabling sub-diffraction-limited imaging and revealing asymmetric hydrogen disks around distant stars.Show Notes UCSD — Nature Biotechnology (xanthomatin biosynthesis)Orca Predation Study — Frontiers in Marine ScienceCivet Coffee Chemistry — Nature Scientific ReportsUCLA Sub-Diffraction Telescope Method — ApJ Letters

    1h 18m

  2. 6D AGO

    FFP EP. 15 | AI-Generated Genomes, Retinal Implants, and Palomar’s Mystery Lights Explained

    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)

    2h 4m

  3. OCT 31

    FFP EP. 14 | Chen Ning Yang — The Man Who Unlocked Symmetry

    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)

    1h 43m

  4. OCT 23

    FFP EP. 13 | Portable Muon Beams, Sodium Batteries, and the Secret to Long Life

    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 BeamNature News CoveragePhysical Review Accelerators and Beams PaperSodium Ion BatteriesScience Daily CoverageJoule Paper (2025)Naked Mole Rats & LongevityBBC CoverageScience Journal Paper

    1h 36m

  5. OCT 15

    FFP EP. 12 | From Princeton to the Nobel Prizes — How FFP Started + 2025 Nobel Recap

    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 Origin Story — Two Princeton friends from different continents unite around a shared love of science and storytelling.The Mission — Creating an “ESPN for Science” that celebrates research and the people behind it.Nobel Follow-ups — Medicine (Tregs and non-immune roles), Physics (macroscopic quantum tunneling and quantum supremacy), Chemistry (MOFs and industrial scaling).Funding + Immigration — Why public research grants and curating global talent are vital to scientific leadership. Show Notes Nobel Prize Press Release (2025 Medicine)Nobel Prize Press Release (2025 Physics)Nobel Prize Press Release (2025 Chemistry)Nature Genetics (2001) — FOXP3 Mutation Causes DysregulationNature (1999) — MOF-5 Discovery (Omar Yaghi et al.)Google Quantum AI Lab — Quantum Supremacy (Nature, 2019)

    1h 12m

  6. OCT 9

    FFP EP. 11 | From Cells to Circuits to Crystals — 2025 Nobel Prizes Unpacked

    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 Medicine: Regulatory T cells and the FOXP3 gene that prevent autoimmune disease.Physics: Macroscopic quantum tunneling and energy quantization in electrical circuits — the bridge to today’s qubits.Chemistry: Metal–Organic Frameworks (MOFs) — modular porous crystals enabling CO₂ capture, water harvesting, and hydrogen storage. Show Notes Nobel Prize Press Release (2025 Medicine) Nature Genetics (2001) — FOXP3 mutation and IPEX link Nature Genetics (2001) — FOXP3 Mutation Causes Dysregulation Nature Genetics (2001) — FOXP3 Gene Cause IPEX Syndrome Science (2003) — FOXP3 function in regulatory T cells German Journal of Immunology (1995) — Sakaguchi’s first Treg paper Nobel Prize Press Release (2025 Physics) Physical Review Letters (1980s) — Macroscopic Quantum Tunneling Experiments (UC Berkeley) BCS Theory (1972 Nobel) — Bardeen, Cooper & Schrieffer, University of Illinois Josephson Effect (1973 Nobel) — Brian D. Josephson Google Quantum AI Lab — Quantum Supremacy Paper (Nature, 2019) Nobel Prize Press Release (2025 Chemistry) Nature (1999) — MOF-5 Discovery (Omar Yaghi et al.) Science (2003) — Reticular Chemistry Foundations Journal of the American Chemical Society (1989, 1990) — Richard Robson’s Early Frameworks Lawrence Berkeley National Laboratory — ChatMOF and AI-Assisted Materials Discovery

    1h 54m

  7. OCT 2

    FFP EP. 10 | AI Supercharges CRISPR & LIGO (Nobel Prize Week Preview)

    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 Stanford Medicine — AI + CRISPR BreakthroughNature Biomedical Engineering — AI-CRISPR Original PaperCaltech — AI Helps LIGOScience — LIGO Machine Learning Paper

    2h 36m

  8. SEP 23

    FFP EP. 9 | China’s AI Breakthrough, Time Crystals, Hidden Viruses, & Brightest Cosmic Signal

    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 • Science Advances: Viral protein structure discovery • Astrophysical Journal Letters: Brightest FRB

    1h 42m
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We break down the week’s biggest science headlines from first principles—because understanding the world shouldn’t require a PhD.

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  • Creator
    Lester Nare and Krishna Choudhary
  • Years Active
    2K
  • Episodes
    16
  • Rating
    Explicit
  • Copyright
    © Lester Nare and Krishna Choudhary
  • Show Website
    From First Principles

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