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!

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 Dysregulation
• Nature (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”).

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

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 Breakthrough
• Nature Biomedical Engineering — AI-CRISPR Original Paper
• Caltech — AI Helps LIGO
• Science — LIGO Machine Learning Paper

Hosted by Lester Nare and Krishna Choudhary, this story explains the first-ever time crystal that humans can actually see, built from liquid crystals at the University of Colorado Boulder. Unlike earlier quantum time crystals that required lasers and extreme cold, this room-temperature, macroscopic version uses simple light to generate a self-sustaining, periodic motion.

Summary

• UC Boulder team builds the first visible time crystal using liquid crystals

• Time crystals explained: symmetry breaking in time vs. space

• Historical context: Frank Wilczek’s 2012 idea and the “no-go theorem”

• Classical vs. quantum systems: why this matters for scalability

• How solitons in liquid crystals act like quasi-particles

• Potential applications: secure currency, dynamic QR codes, photonic devices

• Why room temperature + macroscopic scale make this breakthrough different

Show Notes

• Nature Materials: Visible Time Crystal Study

Hosted by Lester Nare and Krishna Choudhary, this story unpacks China’s DeepSeek R1 — a large language model trained for just $294,000 using restricted H800 GPUs. Published in Nature, DeepSeek shocked the AI community by matching frontier-level performance at a fraction of the cost, and by releasing peer-reviewed papers and open weights. We explore how reinforcement learning without human labels, mixture-of-experts efficiency, and geopolitical strategy made this possible — and why it matters for the global AI race.

Summary

• DeepSeek trained a frontier-scale LLM for only $294K

• First peer-reviewed AI model at this scale (published in Nature)

• U.S.–China AI rivalry: Chips Act, export controls, and geopolitics

• How hardware choke points forced algorithmic innovation

• DeepSeek’s open-weights release vs. OpenAI’s closed approach

• Training strategies: pure reinforcement learning + mixture-of-experts

• Global ripple effects on Meta, OpenAI, and future AI policy

Show Notes

• Reuters: China’s DeepSeek AI paper

• Nature: DeepSeek peer-reviewed paper (1)

• Nature: DeepSeek peer-reviewed paper (2)

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

Hosted by Lester Nare and Krishna Choudhary, this story unpacks brand-new Astrophysical Journal Letters results from JWST hinting at atmospheres on TRAPPIST-1’s Earth-sized planets. We explain how transit spectroscopy works, why TRAPPIST-1 is the perfect laboratory, and what tentative signals of CO₂ and methane could mean for the search for life beyond our solar system.

Summary

• JWST papers show potential atmospheres on TRAPPIST-1 exoplanets

• Transit spectroscopy 101: starlight filtering through atmospheres

• Why TRAPPIST-1’s compact system is ideal for repeated measurements

• Hints of CO₂ and methane amid noise and systematics

• What this implies for habitability and biosignatures

• What’s next: better data, better models, and future observatories

Show Notes

• 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, this story revisits the April headlines claiming the “strongest evidence yet” for life on exoplanet K2-18b. Cambridge researchers reported dimethyl sulfide (DMS) in the planet’s atmosphere using JWST data and atmospheric retrieval models. We unpack why DMS is exciting on Earth, what Bayesian retrieval actually does, and why multiple teams pushed back—arguing the evidence isn’t at the 5-sigma gold standard and could be explained by other gases or model assumptions.

Summary

• BBC-style headline: “Strongest evidence yet” for life on K2-18b

• Cambridge team reports DMS/DMDS signatures via JWST transit spectra

• What DMS means on Earth vs. what it could mean 120 light-years away

• How atmospheric retrieval works (and its limits)

• Why 3-sigma isn’t enough—calls for caution and alternative fits

• Follow-ups suggest a water world; DMS may be abiotic or ambiguous

• Big picture: contrast remote spectral “barcodes” with in-situ rover data

Show Notes

• Cambridge — K2-18b Atmosphere Study

Hosted by Lester Nare and Krishna Choudhary, this story covers NASA’s announcement of potential biosignatures on Mars. Perseverance rover data from Jezero Crater revealed unusual nodules containing iron phosphates and iron sulfides, chemical fingerprints often linked to biological activity. While not definitive evidence of life, the finding represents a huge step forward in astrobiology, highlighting why Mars Sample Return is critical for confirmation — and sparking debates in both the scientific community and pop culture.

Summary

• NASA press conference announces potential biosignatures on Mars

• Perseverance rover at Jezero Crater, Bright Angel Formation site

• Organic search is difficult — radiation + perchlorates destroy compounds

• Scientists instead look for inorganic “life-adjacent” proxies

• Discovery: iron phosphates + iron sulfides linked to carbon gradients

• Instruments PIXL & SHERLOC confirm unusual mineral chemistry

• Debate in Nature peer review: cautious language vs. hype

• Historical context: 1996 ALH84001 “life on Mars” meteorite controversy

• Why sample return is essential for proof

• Funding debate: government + private aerospace collaboration

Show Notes

• NASA — Mars Biosignature Claim

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)