From First Principles

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!SummaryOrigin 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 NotesNobel 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)

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”).SummaryMedicine: 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

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

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 WebbShow 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

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• Atmosphere Study (Paper 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 efficiencyShow NotesSpace.com — 3I/Atlas CoveragePNAS — Longevity Plateau StudyNature Chemistry — No-Sort Plastic CatalystNature — Analog AI

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.SummaryA naked supernova reveals the inner layers of a dying starViruses and bacteria team up to fight cancer with Trojan-horse biologyHarnessing electron spin for ultra-efficient future techScientists engineer bee superfood to save pollinators and agricultureShow NotesCNN — New Supernova DiscoveryNature — Virus+Bacteria TherapyPhys.org — Spintronics StudyBBC — Bee Superfood

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 ChoudharyShow: 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 episodeThe “oldest molecule” puzzle (HeH⁺), cooling the early universe, and why JWST’s findings matterProgrammable proteins: reassigning codons, recoding organisms, and real biosafetyEuropa Clipper’s REASON radar test at Mars: frequencies, ice thickness & ocean cluesDouble-slit, demystified: single photons, “which-path” info, and measurement realityChapters00:00 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👍 Like what you hear? Hit Subscribe, ring the bell 🔔, and drop your questions for next week’s episode.