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.

Summary

• Hypersonics without supercomputers — Stevens Institute validates the Morkovin hypothesis up to Mach ~6 using krypton-tagging velocimetry, confirming that “simple” turbulence models still work in hypersonic regimes and opening the door to viable, inexpensive hypersonic aircraft design.
• Life where it shouldn’t exist — University of Bremen researchers uncover evidence of a chemosynthetic biosphere in the cold, pH-12.6 serpentinizing fluids of the Mariana forearc, offering the clearest Earth analog yet for Enceladus- and Europa-like conditions.
• A millisecond qubit breakthrough — Princeton’s tantalum-on-high-resistance-silicon transmon hits 1.7 ms coherence, 15× the industry norm — drop-in compatible with Google/IBM architectures and a major step toward practical quantum computing.

Show Notes

• Hypersonics — Nature Communications (Stevens Institute)
• Deep Sea Life — Nature Communications Earth & Environment (Univ. of Bremen)
• Princeton Millisecond Qubit — Nature (Transmon Hardware)

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.
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Show Notes

• UCSD — Nature Biotechnology (xanthomatin biosynthesis)
• Orca Predation Study — Frontiers in Marine Science
• Civet Coffee Chemistry — Nature Scientific Reports
• UCLA Sub-Diffraction Telescope Method — ApJ Letters

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

• 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.

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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.

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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