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From First Principles

Lester Nare and Krishna Choudhary
From First Principles
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  • FFP EP. 19 | The Race to the Double Helix — Watson, Crick, Franklin & the Real Story of DNA
    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.SummaryBefore DNA — Mendel’s inheritance laws, Miescher’s nuclein, Levene’s early models, and why scientists initially believed proteins carried heredity.The turning point — Griffith’s transformation experiment and the Avery–MacLeod–McCarty proof that DNA is the genetic material.The physics connection — Schrödinger’s What Is Life? and the idea of an “aperiodic crystal” inspiring Watson, Crick, and a generation of physicists to enter biology.Two labs, one race — Cavendish vs. King’s College, Wilkins vs. Franklin, and the clash of personalities, methods, and interpretations.Photo 51 — Franklin and Gosling’s pivotal diffraction image revealing the helical structure of DNA.The model — base pairing, antiparallel strands, and why the double helix immediately explained replication.Recognition & legacy — the 1953 Nature papers, the 1962 Nobel Prize, Franklin’s omission, and Watson’s later controversies reshaping his legacy.Show NotesMendel (1866) — Pea Plant GeneticsGriffith (1928) — TransformationAvery–MacLeod–McCarty (1944)Schrödinger — What Is Life?Franklin’s Photo 51Watson & Crick (1953)
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  • FFP EP. 18 | 3I/ATLAS Explained, Forensic Fingerprints & Alzheimer’s Breakthrough
    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.SummaryThe third interstellar visitor — 3I/ATLAS joins ‘Oumuamua and Borisov as only the third object ever observed entering the solar system from interstellar space, with new NASA imagery revealing structure, trajectory, and compositional clues.A forensic chemistry breakthrough — researchers at Maynooth University develop a technique to retrieve latent fingerprints from fired shell casings, combining heat-stable organic residues with spectroscopic imaging.A new model of Alzheimer’s — Max Planck Institute scientists uncover a microglial “regulatory” state (a T-reg–like analogue) activated through CD28-dependent pathways, reshaping how the field thinks about plaques, neuroinflammation, and therapeutic targets.Show Notes3I/ATLAS — Interstellar Object Updates (NASA / JPL)Forensic Chemistry: Fingerprints on Fired Casings (Maynooth University)Alzheimer’s Microglia Study — Max Planck Institute / Univ. of Cologne
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  • FFP EP. 17 | Hypersonic Physics, Deep Sea Life & Princeton’s Millisecond Qubits
    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.SummaryHypersonics 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 NotesHypersonics — Nature Communications (Stevens Institute)Deep Sea Life — Nature Communications Earth & Environment (Univ. of Bremen)Princeton Millisecond Qubit — Nature (Transmon Hardware)
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  • 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.SummaryUCSD’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 NotesUCSD — Nature Biotechnology (xanthomatin biosynthesis)Orca Predation Study — Frontiers in Marine ScienceCivet Coffee Chemistry — Nature Scientific ReportsUCLA Sub-Diffraction Telescope Method — ApJ Letters
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  • 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 MysteriesHosted 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)
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