From First Principles

Can light restore aspects of sight? Can recalling a cold experience change an animal's metabolism? And what can ghost particles and mirror-image molecules tell us about the universe?

Lester Nare and Krishna Choudhary follow up on our 2026 Nobel Prize episodes with research building on optogenetics, IceCube and molecular handedness. We unpack an early human vision-restoration trial, cold-memory experiments in mice, cosmic neutrino flavors, and a tiny electrical sensor for distinguishing left- and right-handed amino acids.

Plus: how the Nobels work, our follow-up on the Nobel chemistry illustration, a brief look at neutrino Earth tomography, and...

Why does life favor one molecular mirror image? The 2026 Nobel Prize in Chemistry honors Henri B. Kagan and Kenso Soai for nonlinear effects and autocatalysis in asymmetric organic synthesis.

Lester Nare and Krishna Choudhary unpack the science from first principles: chirality, Pasteur's crystals, enantiomeric excess, and how a tiny imbalance can grow into an overwhelming preference for one molecular hand.

We connect Kagan's catalyst discoveries and the Soai reaction to medicines, the origins of biological handedness, and the serious concerns around hypothetical mirror life. Plus: symmetry in physics, Frances Oldham Kelsey and thalidomide, and our...

Why build a telescope inside a billion tons of Antarctic ice? The 2026 Nobel Prize in Physics recognizes Francis Halzen's work on IceCube and the discovery of high-energy neutrinos from the cosmos.

In Episode 62 of From First Principles, Lester Nare and Krishna Choudhary explain neutrinos from the ground up: why these elusive particles make powerful cosmic messengers, how faint flashes of Cherenkov light reveal their interactions, and why detecting them requires an observatory buried deep beneath the South Pole.

We follow the path from beta decay and the first neutrino experiments to AMANDA, IceCube's construction, the 2013...

How do you prove what a brain cell actually does? The 2026 Nobel Prize in Medicine celebrates a remarkable answer: give cells a light-sensitive protein, then switch their activity on or off with light.

In Episode 61 of From First Principles, Lester Nare and Krishna Choudhary explain optogenetics from the ground up and trace the discoveries of Peter Hegemann, Georg Nagel and Karl Deisseroth. We follow the story from algae swimming toward light to channelrhodopsins, precisely controlled neurons, and experiments probing memory, reward and behavior. Then we explore heart-brain connections, early attempts to restore vision, and...

Who could win the 2026 Nobel Prizes? From the science behind Ozempic to quantum interference and droplets inside living cells, Lester Nare and Krishna Choudhary make their picks for Medicine, Physics and Chemistry, and explain the discoveries behind them.

In Episode 60 of From First Principles, we explore seven research areas with a case for Nobel recognition: GLP-1, optogenetics, optical coherence tomography, the Aharonov–Bohm effect, atomic force microscopy, biomolecular condensates and Buchwald–Hartwig coupling. We also discuss Michael Berry’s geometric phase and the awkward question of how a prize limited to three people recognizes discov...

What connects a noise complaint, holiday lights seen from space, and the physics of a coffee stain? Three unexpected paths from basic research to discoveries with real-world impact.

Krishna Choudhary and Lester Nare explore the science behind the 2026 Golden Goose Awards: Zhen Xu's work on histotripsy, NASA's Black Marble nighttime satellite data, and Sidney Nagel's discoveries in soft matter physics.

We start with focused ultrasound and the tiny bubbles that can break apart targeted tissue, tracing the journey from early laboratory experiments to clinical research on liver tumors. Then...

What does it mean to solve an equation that describes almost every fluid around us, from the air over a wing to the water swirling down a drain?

In Episode 58 of From First Principles, Lester Nare and Krishna Choudhary build the Navier-Stokes equations from the ground up before digging into OpenAI’s claimed breakthrough and the debate surrounding it.

Summary

What science should you be watching this fall? From Nobel Prize season to NASA’s Roman Space Telescope, Mars’ moons and Mercury, Lester Nare and Krishna Choudhary take a relaxed tour of the discoveries and missions on their radar.

In Episode 57 of From First Principles, we explore why curiosity-driven research matters, what the Golden Goose Awards celebrate, and how questions that once sounded impractical can lead to unexpected breakthroughs. Then we turn to space: Roman’s search for dark energy and exoplanets, JAXA’s Martian Moons eXploration (MMX) mission, and the mysteries ESA and JAXA’s BepiColombo mission wi...

What can a yak living thousands of meters above sea level teach us about repairing the human brain?

In Episode 56 of From First Principles, Lester Nare and Krishna Choudhary break down a new Neuron paper that traces an evolutionary adaptation found in high-altitude animals to a previously hidden pathway involved in building and repairing myelin.

Summary

Which quantum computer will actually scale?

In Part 2 of our quantum computing deep dive, Lester Nare and Krishna Choudhary move from theory to hardware—comparing superconducting qubits, trapped ions, neutral atoms, and silicon spin qubits before going inside the new Nature cover paper Krishna co-authored with the HRL Quantum Team and collaborators.

The episode begins with a simple question: what makes a good quantum computer? We evaluate each architecture using three criteria: qubit quality, qubit control, and scalability and economics.

Superconducting qubits offer extremely fast operations, but scaling them introduces challenges involving microwave co...

Quantum computers do not simply “try every answer at once.” So what do they actually do—and why have governments and technology companies spent billions trying to build them?

In Part 1 of our two-part quantum computing deep dive, Lester Nare and Krishna Choudhary build the field from first principles.

The series was prompted by a new Nature cover paper, A digitally controlled silicon quantum processing unit, co-authored by Krishna and members of the HRL Quantum Team and collaborators. Before getting into that hardware in Part 2, we first need to understand why anyone wanted to build a quan...

Claude did not solve the Riemann Hypothesis. But what it actually did may be one of the clearest examples yet of how rapidly AI systems are changing the way difficult mathematics can be attacked.

In Episode 53, Lester Nare and Krishna Choudhary go from first principles on arguably the most famous unsolved problem in mathematics.

We begin with Euler and the Basel problem, build the Riemann zeta function from the ground up, explain its deep connection to prime numbers, move into the complex plane and analytic continuation, unpack the famous 1 + 2 + 3 + 4 + … = -1/12 result, and finally arrive at th...

In this anniversary episode, Lester Nare and Krishna Choudhary look back at how two longtime friends turned their regular conversations about science into a show now shared by millions of people around the world, and what they hope to build with FFP Nation in Year Two.

Then we turn to a new Nature paper challenging the idea that the precolonial Amazon was sparsely populated. Airborne LiDAR revealed hundreds of geometric earthworks hidden beneath the rainforest canopy. Combining the new survey with earlier archaeological evidence, the researchers estimate that the region could contain more than 20,000 earthworks and may...

What happens when electronics can operate at temperatures hot enough to melt aluminum?

In this deep-dive episode, Lester Nare and Krishna Choudhary examine a new high-temperature memory device developed by researchers at USC, the Air Force Research Laboratory, Kumamoto University, and their collaborators.

Published in Science, the experimental memristor combines tungsten, hafnium oxide, and graphene. It operated reliably at 700°C—roughly 1,300°F—retained data for more than 50 hours, and survived more than one billion switching cycles.

We begin by explaining why conventional electronics and flash memory fail when temperatures rise. From deep-earth drilling and hy...

Hosted by Lester Nare and Krishna Choudhary, this episode moves from astrobiology to science policy to the rapidly changing frontier of artificial intelligence and mathematics.

First, researchers analyzing pristine samples returned from asteroid Ryugu report all five canonical nucleobases used by DNA and RNA. We explain what that does—and does not—mean for the origin of life, how JAXA’s Hayabusa2 mission collected uncontaminated asteroid material, and why comparisons with NASA’s Bennu samples strengthen the case that prebiotic chemistry may be widespread across the Solar System.

Next, we examine the fight over who controls...

In this special interview episode, Lester Nare speaks with Juan Busso, Senior Football Data Scientist at FIFA, and Arron Ackerman, FIFA’s Team Lead for Football Performance Analysis, about the data science behind the Match Momentum visualization featured throughout the 2026 World Cup.

What does “momentum” actually mean in football—and how can it be measured without reducing the game to possession or shots? Juan and Arron explain how FIFA translates football principles into mathematical models, validates those models with coaches and technical experts, and turns complex tracking data into a graphic that fans can understand at a glance.<...

Hosted by Lester Nare and Krishna Choudhary, this episode returns to the FFP science rundown with stories spanning astrophysics, precision medicine, medical imaging, artificial intelligence, and World Cup technology.

We begin with the Event Horizon Telescope and its evolving view of M87*, the supermassive black hole 55 million light-years away. How do you image something that appears about as small as a donut on the Moon? Krishna explains angular resolution, the Rayleigh limit, radio interferometry, and how telescopes across Earth can function like one planet-sized instrument. We then look at new observations showing the magnetic field around M87...

Hosted by Lester Nare and Krishna Choudhary, this episode is part two of our July 4th America 250 special: a celebration of the scientific, technological, institutional, and cultural breakthroughs that helped shape the United States into one of the most important scientific nations in human history.

In part one, we traced American science from Benjamin Franklin and the founding documents through Sputnik, NASA, DARPA, Bell Labs, the transistor, information theory, nuclear physics, molecular biology, and the birth of the modern American science state. In part two, we pick up after Sputnik and follow the explosion of American science...

Hosted by Lester Nare and Krishna Choudhary, this episode is part one of our July 4th America 250 special: a celebration of the scientific, technological, institutional, and cultural innovations that helped shape the United States into one of the most important scientific nations in human history.

For America’s 250th anniversary, we built an interactive timeline of the discoveries, inventions, institutions, and funding systems that enabled American science to grow from Benjamin Franklin’s experiments with electricity into the age of NASA, DARPA, Bell Labs, nuclear physics, molecular biology, modern computing, and big science.

In part one...

Hosted by Lester Nare and Krishna Choudhary, this episode is our World Cup special — a deep dive into the science, physics, engineering, and data behind the beautiful game.

We start with the offside rule and the controversy around semi-automated VAR. How can a system decide whether a player is onside or offside by only a few inches? Krishna breaks the problem down like an experimental physicist: player speed, ball-contact time, camera frame rate, significant digits, and the error budget behind the line on screen. From there, we get into the actual technology: player tracking, digital twins, high-resolution ca...

Hosted by Lester Nare and Krishna Choudhary, this episode marks Krishna’s return to the studio after paternity leave — and the timing could not be more fitting. Today’s deep dive is about inheritance: not just the classic Mendelian rules most of us learned in biology class, but the stranger, more dynamic world of non-Mendelian epigenetic inheritance.

Starting from Gregor Mendel and his pea plants, Lester and Krishna rebuild the foundations of genetics from first principles: dominant and recessive alleles, Punnett squares, chromosomes, fruit flies, DNA, and the physical mechanism behind inherited traits. Then they move into the “s...

Hosted by Lester Nare and Krishna Choudhary, this episode is the second interview in our ongoing collaboration series with Carnegie Observatories. Krishna sits down with Dr. Michael Blanton, the new Director of the Carnegie Observatories, for a wide-ranging conversation on how astronomy became one of the most data-rich sciences, how the Sloan Digital Sky Survey helped change the culture around open data, what the next era of astronomical data science and AI could look like, and one of the galaxy mysteries Blanton still wants to solve: why the most massive galaxies in the universe stop forming stars.The conversation...

Hosted by Lester Nare, this episode features astrophysicist Dan Gilman for a deep conversation on one of the biggest open questions in modern physics: what dark matter actually is. Starting from first principles, Lester and Dan walk through why the evidence for dark matter is now so strong, how strong gravitational lensing works, why tiny distortions in lensed light can reveal invisible clumps of matter, and how the next generation of surveys may transform the field. Krishna is out on family leave for this one, but the conversation stays fully in the From First Principles lane: grounded, visual, and...

Hosted by Lester Nare and Krishna Choudhary, this interview features John Mulchaey, the 12th President of Carnegie Science and former Director of the Carnegie Observatories. The conversation starts with his early work on galaxy groups and dark matter, then expands into how Carnegie works as a scientific institution, what the Giant Magellan Telescope could unlock for exoplanets and astronomy, how science funding actually works, and why eclipse chasing is still one of the most magical experiences in science.

Summary

Galaxy groups and dark matter — Mulchaey explains why small galaxy groups matter more than most people re...

Hosted by Lester Nare and Krishna Choudhary, this rundown episode covers four new science stories at a high level: a huge new 3D ant imaging database built with synchrotron X-ray microtomography, a lunar agriculture experiment that grew chickpeas in simulated moon soil using fungi and worm waste, AI-assisted discovery of strange objects in the Hubble archive, and a new programmatic roadmap for room-temperature superconductivity. There is also another round of Are You Smarter Than a Scientist? in the middle.

Summary

Particle accelerators meet biodiversity — researchers built a massive high-resolution an...

Hosted by Lester Nare and Krishna Choudhary, this special episode ranks the 26 scientists shown in Christopher Nolan’s Oppenheimer by one standard only: their contribution to fundamental science. Starting with the Manhattan Project figures near the bottom and working up through the giants of quantum mechanics, relativity, nuclear physics, and logic, the episode turns a movie cast list into a surprisingly deep walk through the history of modern physics.

Summary

A ranking framework that actually means something — this list is based on scientific achievement, not movie prominence, clout, or vibe...

Hosted by Lester Nare and Krishna Choudhary, this episode is a deep dive into one of the strangest and most hard-fought materials science stories in decades: the claim that researchers have finally synthesized bulk hexagonal diamond, also known as lonsdaleite. They break down why this material matters, how it differs from ordinary cubic diamond, why scientists argued about its existence for more than 50 years, and what the new Nature paper actually did to convince skeptical reviewers.

Summary

Why hexagonal diamond matters — if real, it is a long-sought carbon phase th...

Hosted by Lester Nare and Krishna Choudhary, this episode is a full deep dive on Artemis II as the crew returns from humanity’s first crewed lunar flyby in more than 50 years. Lester and Krishna break down the mission photo by photo, from launch and translunar injection to Earthset, Earthrise, the in-space solar eclipse, the science of lunar observations, and the skip-entry reentry profile bringing Orion home.

Summary

Why Artemis II is historic, what the crew saw on the far side of the Moon, and why this mission matters fo...

Hosted by Lester Nare and Krishna Choudhary, this rundown episode covers five new science and tech stories at a high level: NASA’s Artemis 2 moon mission, what actually leaked in the Claude Code incident, a new cancer genomics paper suggesting domesticated cats may be unusually useful real-world models for human cancer, two leaked iPhone spyware toolkits, and a science-focused review of Project Hail Mary.

Summary

Artemis 2 is finally flying — why this mission matters, why it is not landing yet, and why the moon race is back in geopolitical focus.

Hosted by Lester Nare and Krishna Choudhary, this episode is a deep dive into one of the hardest questions in neuroscience: what breaks in the brain during a coma, and can we figure out how to turn consciousness back on? We unpack a new paper from Daniel Toker et al. that uses an interpretable AI framework — not a generic black box chatbot model — to reverse engineer the biological mechanisms of prolonged unconsciousness, recover known features of coma, predict new ones, and propose a possible new target for deep brain stimulation.

Summary

Hosted by Lester Nare and Krishna Choudhary, this episode is a fast-moving science rundown covering four remarkable stories from across AI, genetics, neuroscience, and paleontology. We dig into the story of a machine learning engineer who used AI tools to help design a personalized cancer vaccine for his dog, explore how an all-female fish species has survived far longer than evolutionary theory would predict, unpack new brain-scan evidence for how ketamine may rapidly relieve severe depression, and look at new research suggesting life rebounded shockingly fast after the asteroid that killed the dinosaurs.

Summary<...

Hosted by Lester Nare and Krishna Choudhary, this episode is a deep dive into one of the strangest science stories of the year: a dish of human neurons allegedly learning to play Doom. We go back to the original 2022 DishBrain paper out of Cortical Labs, unpack how biological neurons can be read and written with multi-electrode arrays, and then compare the peer-reviewed Pong result to the much newer Doom claim. The result is a story that is both genuinely impressive and, in places, probably overhyped.

Summary

Wetware engineering — replacing ar...

Hosted by Lester Nare and Krishna Choudhary, this is our first standalone rundown episode — a faster, looser format where we hit several stories we didn’t have room to turn into full deep dives. This week: bacteria revived from a Romanian ice cave after 5,000 years, a speculative but fascinating theory linking solar storms to earthquakes, new evidence that dogs and humans share genetic roots for personality traits, and the increasingly dramatic fight over the future of AI after Yann LeCun leaves Meta to build a new billion-dollar company focused on world models.

Summary

Hosted by Lester Nare and Krishna Choudhary, this episode is a deep dive into a new synthetic-biology breakthrough out of EPFL: OptoEvolution. The big idea is simple but powerful — traditional directed evolution is great at making proteins that are always “on,” but biology is full of proteins that need to switch states, respond to stimuli, and behave more like logic gates than static tools. This paper takes directed evolution and couples it to light and the cell cycle, creating a new way to evolve dynamic proteins that can toggle, compute, and respond with far more control.

Summary

Hosted by Lester Nare and Krishna Choudhary, this episode is a full deep dive on planetary defense. We break down NASA’s DART mission, why the goal was never to “blow up” an asteroid but to gently nudge it, and why the newest result is even bigger than the original headline: scientists can now directly detect that the Didymos–Dimorphos system changed not just locally, but in its heliocentric path around the Sun.

Summary

Hosted by Lester Nare and Krishna Choudhary, this episode starts in astrobiology with a fresh experimental challenge to one of the biggest objections to lithopanspermia: can life actually survive the violence of being blasted off a planet by an asteroid impact? Then, after a packed Rundown, we pivot hard into immunology with a radical Stanford paper asking whether we could build one nasal vaccine that doesn’t target a specific pathogen at all—but instead makes the lung itself a stronger fortress against whatever shows up.

Summary

Lithopanspermia gets less...

Hosted by Lester Nare and Krishna Choudhary, this episode has two main stories: an astrophysics update on a candidate “dark galaxy” in the Perseus Cluster (a halo that’s ~99.9% dark matter), and a major Alzheimer’s mechanism paper tracing how exercise protects the brain by repairing the blood–brain barrier—with an actionable drug-like path already emerging.

Summary

Candidate dark galaxy — Hubble + Euclid stacking and globular clusters reveal an ultra-faint halo that could test missing satellites and the cusp–core problem (and even “fuzzy dark matter”).

Exercise → Alzheimer’s mechanism...

Hosted by Lester Nare and Krishna Choudhary, this episode has three main stories: interactive dream engineering (yes, two-way “communication” during lucid dreaming), the proton radius puzzle finally getting resolved by a precision lab measurement, and a sobering but hopeful look at ALS—including a breakthrough “ALS-in-a-dish” model that could finally make drug screening translate to humans.

Summary

Hosted by Lester Nare and Krishna Choudhary, this episode is a Winter Olympics deep dive from first principles—physics, neuroscience, and climate science in one ride.

• Why ice is slippery: the “water layer” story is incomplete—new nanoscale measurements suggest a far more viscous, thicker interfacial film than textbook intuition.
• Choking under pressure: how high stakes can disrupt neural control—reward signals can push brain states out of the “optimal zone.”
• Climate change vs winter sports: why artificial snow has limits, why some legacy venues may become unreliable, and what “snow farming” is trying to solve.
• Rundown: AI...

Hosted by Lester Nare and Krishna Choudhary, this episode jumps from plant biochemistry to quantum metrology to cancer evolution. We start with a University of York breakthrough that solves a ~50-year mystery in alkaloid biosynthesis—identifying the “missing” enzyme behind a key asymmetric step plants use to build powerful defensive (and pharmaceutically useful) molecules. Then we go deep on quantum sensing with entangled atomic clouds, showing how correlated measurements can beat the standard quantum limit. Finally, we close with ALFA-K, a new tool that maps local fitness landscapes to predict how aneuploid cancers may evolve under pressure from therapy.

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