Advertise on podcast: The Pauling Principle

In this episode I sit down with Karmen Čondić-Jurkić, co-founder and Executive Director of the Open Molecular Software Foundation, the organization behind OpenFE, Open Force Field, OpenFold, and OpenADMET. We talk about what it takes to build scientific software that a dozen competing pharma companies will fund together, why permissive MIT licensing beats the walled garden, and how a recent blind challenge put OpenFE's binding free energy predictions in front of the whole field for independent scrutiny.

I sat down with Christopher Bradley, CEO and Co-Founder of Matter Bio, a company working at the intersection of longevity science and oncology. Christopher co-founded Matter Bio alongside Harvard geneticist George Church with a central thesis: that the secret to human longevity lies in genomic integrity, and that the best teachers are the organisms that have already solved it. Their ongoing research draws on genomic data from over 10,000 centenarians, 20,000 of their relatives, and more than 300 species, including the remarkable 400-year-old Greenland shark. We recorded this episode fresh off a major milestone for Matter Bio: FDA clearance of their IND application for LM-LLO-TT, their attenuated Listeria-based immunotherapy targeting pancreatic ductal adenocarcinoma. PDAC is one of the deadliest and hardest-to-treat cancers, and this approval opens the door to their first-in-human Phase 1/2a trial. It is the culmination of nearly a decade of scientific and clinical work, and a meaningful proof point that Matter Bio's platform is ready to meet patients where they need it most. Christopher brings a rare combination of backgrounds: neuroscience training at Rutgers, graduate research in fMRI at NYU, and a track record as a serial entrepreneur who previously built and sold Mana Health to Comcast NBC Universal. Enjoy the conversation!

Most doctors treat you after you get sick. Professor Andrea Maier is trying to make sure you never get there. In this episode, I sit down with one of the world's leading longevity scientists, a biogerontologist who holds professorships across three continents, founded the Healthy Longevity Medicine Society, and co-founded Chi Longevity Clinics in Singapore. We explore why aging itself is becoming a treatable condition, how biological aging clocks are changing the way we think about health, and what it actually takes to bring longevity medicine out of luxury clinics and into everyday practice. This is a conversation about the science, the clinical reality, and the future of growing older on your own terms.

In this episode of The Pauling Principle I sit with Marco Quarta, Founder and current CSO of Rubedo and we discuss cellular senescence, one of the most prominent causes of aging, and a variety of potential therapies. As well as Rubedo recent positive phase I clinical trial.

In this episode I sit down with Professor Hugo Verli, one of the pioneers in computational chemistry. And we discuss the past, present, and future of the field. Including some of the key challenges, like how to simulate carbohydrates and highly dynamic molecules. What simulations would YOU like to run? let me know in the comments! :)

Designing functional RNA for therapeutics is notoriously hard, but gRNAde changes the game. This geometric deep learning model generates high quality RNA sequences from target 3D structures. It outperforms Rosetta, slashes design time to seconds, and hits 50% success in wet-lab tests on complex folds. Chaitanya Joshi, lead author of the paper, joins us to share how gRNAde is speeding up RNA-based medicines and programmable biology.

What if aging itself is the disease we should be curing? In this episode, I sit down with Aubrey de Grey, the legendary biogerontologist who has spent decades arguing that aging is not an inevitable fate but an engineering problem with solvable components. We dive into the science behind his SENS framework, explore why the longevity field is finally gaining mainstream momentum, and debate just how close we are to adding decades of healthy life to the human lifespan. Whether you're a skeptic or a true believer, this conversation will challenge how you think about mortality, medicine, and what it means to grow old. Aubrey is also someone that I admire deeply, so I hope you find this conversation interesting!

Antibody design is one of the most exciting challenges in AI drug discovery. After Alphafold solved many of the problems of protein structure prediction, researchers moved their attention to protein structure design, and antibodies in particular are one of the most interesting proteins that we would like to design. Both because of the impact in patients as well as massive commercial potential. Join my chat with Santiago Mille from Stanford University about Germinal, a novel pipeline for antibody design.

In this episode, I sit down with Dr. Maria Marinova to uncover one of the most misunderstood frontiers in human biology: female reproductive aging. We break down why female fertility declines, what’s actually happening at the cellular level, and the emerging science that suggests this decline may be reversible. Not someday in the distant future, but now.

Matt Kaeberlein is one of the world’s leading scientists in aging biology. He is a biogerontologist with 250+ publications, former University of Washington professor, and co-founder of landmark initiatives like the Dog Aging Project. In this episode, we dive into the real mechanisms of aging, how scientific discovery actually happens, where longevity research is going next, and why much of what people believe about “anti-aging” is wrong. If you’re interested in living longer, staying healthier, or understanding the future of biomedical science, this conversation will challenge your assumptions and give you a clearer view of what the next decade of longevity research might actually look like.

Is protein folding solved? Not quite, even though the progress has been tremendous since the first AlphaFold and up to last year's Nobel prize. The team behind Boltz and Boltz-2, from MIT CSAIL and Jameel Clinic, just released Boltzgen, a state of the art model for protein design. In this chat with Gabriele Corso I review the progress in the field and whats next.

Shantanu Singh is one of the principal investigators at the celebrated Broad Institute of MIT and Harvard. His research is centered around finding “fingerprints” of genes, chemicals and diseases from microscopy images of cells. Which has tremendous applications for drug discovery and curing diseases. I hope you enjoy this episode! Also check out some more links about his work below: About the Lab: - Carpenter-Singh Lab: https://carpenter-singh-lab.broadinstitute.org/ - MIT Technology Review article on Cell Painting / JUMP Consortium: https://www.technologyreview.com/2023/03/03/1069261/a-technique-called-cell-painting-could-speed-drug-discovery/ - Recent review of Cell Painting applications: https://rdcu.be/d2vHH Resources: - Cell Painting Gallery (open image datasets): https://www.nature.com/articles/s41592-024-02399-z - OASIS Consortium (liver toxicity prediction and reducing animal testing): https://oasisconsortium.org/ Additional Reading: - On our two-PI lab model: https://www.asbmb.org/asbmb-today/people/083122/high-affinity-binding

Andy and his team at Vincere have been doing amazing work over years to figure out the mitochondrial mechanisms that may contribute to Parkinson's and other neurodegenerative diseases. Listen in as we discuss curing Parkinson's, using AI to find new molecules and broader drug discovery.

Andrew White and his team at Future House have one of the most ambitious missions. I'll quote here because I couldn't say it better myself: Our mission is to build an AI scientist, or AI systems, that can automate scientific research and accelerate the pace of discovery, so humanity can find cures for disease, solutions for climate change, and other species-accelerating technologies. Must watch! 👀

What if the biggest breakthroughs in health and biotechnology aren’t waiting on new ideas but on better experiments? In this episode, Michael Florea joins Javier to expose the hidden bottlenecks in animal research, the quiet revolution of automation in the lab, and the radical possibilities of treating DNA itself as medicine. This conversation peels back the curtain on how science really moves forward and why the future of drug development may look nothing like today.