From First Principles

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* changing over time—and why that may help explain black-hole jets and the mysterious shutdown of star formation in giant elliptical galaxies.
Next, we turn to medicine. Researchers at Johns Hopkins have built personalized digital twins of patients’ hearts, allowing doctors to simulate ventricular-tachycardia treatments before entering the operating room. We break down how MRI data, electrical modeling, and virtual ablation could reduce procedures from hours to roughly 30 minutes. We also examine Midjourney Medical’s proposed whole-body ultrasound scanner: what the prototype appears to do, what its creators are claiming, and why it should be viewed as a potential addition to the medical-imaging toolbox rather than a replacement for MRI.
Finally, we return to the World Cup. Krishna takes on “Are You Smarter Than a Scientist?” by guessing the most common injuries in professional football. Then we investigate the Norway–England Skycam controversy: did the ball strike a cable, and why did its internal sensor appear not to detect it? We close with the data behind home-field advantage, referee bias, and the natural experiment created by crowdless matches during the COVID-19 pandemic.
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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 from 1958 to today.
This episode covers the visual system, solar wind, perceptrons, impact cratering, pacemakers, neurotransmitter reuptake, cochlear implants, the genetic code, quarks, Bell’s theorem, density functional theory, the fast Fourier transform, immigration policy, electroweak unification, ARPANET, Apollo 11, dark matter, MRI, GPS, Unix, gravitational waves, ozone depletion, lithium batteries, Voyager, RNA splicing, recombinant insulin, quantum computing, the Space Shuttle, prions, PCR, cellular networks, telomeres, laser cooling, backpropagation, the Hubble Deep Field, Deep Blue, Sagittarius A*, cosmic acceleration, the Human Genome Project, CRISPR, mRNA vaccines, reusable rockets, LIGO, transformer models, black hole imaging, quantum supremacy, and the James Webb Space Telescope.
The larger story is not just that America produced extraordinary discoveries. It is that those discoveries came from an ecosystem: universities, national labs, government agencies, industrial research labs, immigrant scientists, public investment, basic research, private enterprise, and a culture that repeatedly turned curiosity-driven science into civilization-changing technology.
The episode closes by connecting that 250-year legacy to the current debate over federal science funding and the future of American scientific leadership.
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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, we go from Franklin’s discovery of the conservation of charge in 1747 through the Sputnik crisis in 1958. Along the way, we cover the Declaration of Independence, the Constitution’s science and patent clause, the first federal scientific agency, the rise of medical journals, the American system of manufacturing, the telegraph, anesthesia, land-grant universities, the telephone, Edison’s industrial R&D lab, the Michelson-Morley experiment, alternating current, the Wright brothers, the discovery of galaxies, the Manhattan Project, the transistor, information theory, the polio vaccine, the integrated circuit, and the mobilization of American science after Sputnik.
This is not just a list of inventions. It is a story about compounding infrastructure: universities, journals, patents, philanthropy, federal agencies, industrial laboratories, war mobilization, immigrant scientists, basic research funding, and the feedback loop between science, technology, government, and culture.
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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 cameras, and the connected match ball sensor that helps determine when the pass was played.
Then we move from refereeing technology to the ball itself. Why does the 2026 World Cup ball look the way it does? How do Platonic solids, panel geometry, and surface seams affect the way a soccer ball flies? And why was the 2010 Jabulani ball so controversial? We go through drag, drag coefficients, wind tunnels, the drag crisis, golf ball dimples, and why the roughness of a ball can completely change its trajectory.
Finally, we look at the hidden engineering of the World Cup pitch — real grass in NFL stadiums, LED grow lights, drainage systems, turfgrass science, and even 3D-printed cleat-foot testing devices — before ending with match momentum, possession value, hydration breaks, and the data science behind modern football analytics.
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Show Notes
Semi-automated offside technology and connected-ball systems
Adidas Trionda — official 2026 World Cup match ball
Aerodynamics of World Cup balls and the Jabulani drag-crisis controversy
World Cup 2026 pitch engineering and turfgrass research
Possession value and match momentum in football analytics

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 “software layer” of biology: epigenetics, DNA methylation, chromatin packaging, RNA interference, and paramutation — cases where the genetic code is present, but the cell’s machinery silences or rewrites how that code is used.
The episode centers on a new Nature Genetics paper, “Non-Mendelian inheritance of DNA methylation patterns in mice,” which suggests that non-Mendelian epigenetic inheritance may be more widespread in mammals than previously understood. The conversation also covers why Oxford Nanopore sequencing made this kind of analysis possible, why methylation patterns can be hard to trace across generations, and what all of this could mean for disease risk, drug response, sex differences, evolution, and the long-running nature-versus-nurture debate.

Summary
Mendel’s rules — how pea plants, true-breeding lines, dominant and recessive traits, and Punnett squares gave us the first mathematical laws of inheritance.
The first cracks in Mendel — how chromosomes, fruit flies, sex-linked traits, and linked genes showed that inheritance is more complicated than independent assortment.
DNA as hardware, epigenetics as software — why having a gene is not the same thing as expressing it, and how methylation and chromatin packaging can silence parts of the genome.
Paramutation — how one allele can change the expression state of another allele across generations, creating inheritance patterns that do not follow standard Mendelian expectations.
Oxford Nanopore and the technology shift — why long-read sequencing and direct methylation detection make it possible to trace epigenetic marks back to the parent they came from.
The mouse methylation paper — how researchers used collaborative cross mice to show that most methylation inheritance looks Mendelian, but a meaningful fraction appears to follow stranger non-Mendelian rules.
Why it matters — potential implications for clinical genetics, disease risk, drug efficacy, sex-specific biology, and the relationship between nature and nurture.
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