Ground Truths

Vadim Gladyshev, PhD, Professor of Medicine at Brigham and Women's Hospital, Harvard Medical School, elected to the National Academy of Science, is a prolific science of aging researcher. We covered many topics including:

—The nature of aging, and how it is different from biological aging (with glossary below)

—The clocks of biological aging, which he considers biomarkers

proteomic organ clock paper

transcriptomic clock paper

mAge (multimodal) clock with wearable preprint

facial clock (and others to come such as voice, videos)

metabolomic clock paper (from...

Michael Lewis is one of the best storytellers of our era. You know and likely have read his books Moneyball, The Big Short, The Blind Side, Flash Boys, Liar’s Poker, and The Undoing Project, to name a few. He has long been one of my favorite authors.

This was the first interview that Michael did on his new book, BLOCKERS, published on October 6th, streamed live on Substack Sept 29th. It’s his 21st book and 4 of the last 5 have been about the US government: The Fifth Risk (2019), Premonition (2021), and Who Is Government? (2025).

Hi...

In recent weeks the results (announced by press release) of 2 major placebo-controlled randomized trials—ZEUS, testing an interleukin-6 (IL-6) blocker vs inflammation, and HORIZON, testing a drug to lower Lp(a), indicated failure to achieve their primary endpoint.

Are we maxxed out for new treatments vs heart disease, as this article in the WSJ (←gift link) today asserts?

“Cardiovascular drug development is starting to look a bit like the modern oil industry. The easy wells have been tapped. What’s left is in deep water: expensive, technically perilous and less likely to strike oil.”

This podcast is meant to complement my recent Ground Truths post Why Our Memory Slips After Age 50 which has all the relevant links to the 2 papers, key graphics, and other related publications. If you haven’t had a chance to read that, it would be helpful to spend a few minutes to do so before listening to this podcast.

Links to the 2 papers for those who don’t want to look back

Zemke et al in Science https://www.science.org/doi/10.1126/science.adt8307

Belk et al in Nature https://www.nature.com/arti...

Deb Cohen is an award winning investigative journalist and correspondent who trained as a physician and has worked with the BBC and BMJ. She just published BAD INFLUENCE, a book which takes us deep into the wellness-industrial complex—the confluence of the supplement, testing, tech, and pharma industries, and how they sell health anxiety to healthy people.

Here are some of the points we discussed:

—The big market in healthy, well people. Tests, wearables, imaging, supplements, etc

—Algorithms feed the health anxiety in an amplifying, vicious loop on the social media platfo...

Sarah Urbut is a physician-scientist at Harvard Medical School and the Massachusetts General Research Institute. She and her colleagues published a landmark paper in Nature on patient health journeys for 3 different cohorts—the Mass General Brigham patients, the UK Biobank, and the All of Us research program—with a cumulative 683,000 individuals, 348 diseases, and up to 52 years of follow-up. Integrating electronic medical records and polygenic risk scores (N=36). An AI model was developed and validated called ALADYNOULLI, with each individual represented latent disease signatures (N=21), mathematically and biologically driven. An example of a patient’s dynamic life journey (health arc) is pro...

“The future of biology is programmable.”

To give you a sense of how important this topic is, Patrick Hsu is the first guest we’ve had back to Ground Truths since the podcast began a few years ago. Nearly 2 years ago we spoke about digital biology but so much has happened since to help unravel the complexities in the language of life.

Patrick is a co-founder and core investigator at the Arc Institute. His work is at the intersection of biology, engineering, and AI. At the ripe old age of 33, he’s a pioneer of genome e...

The tumor microenvironment (TME), composed of immune cells, fibroblasts, and endothelial cells, has emerged as critical to pathogenesis, prognosis and treatment for cancer (schematic Figure below). There’s no such thing as TMI (too much information) for TME! Yet there’s still no way of assessing it in the clinic by a blood test, and even by invasive biopsy the sampling bias for TME without broader geographic context can lead to important mistakes. That isn’t used for clinical decision making. The TME field is about to change.

Recently, Professor Aaron Newman at Stanford and colleagues from many U...

“I may be the expert in cancer, but you are the expert in you.”—Elisa Port, MD

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Dr. Elisa Port is Professor of Surgery, Icahn School of Medicine at Mount Sinai; Chief of Breast Surgery for the Mount Sinai Health System; Director of the Dubin Breast Center; and Director of the Center of Excellence for Breast Cancer at the Mount Sinai Tisch Cancer Center, a NCI-Designated Compre...

Helen Pearson, PhD, is an award-winning biomedical journalist at Nature, named European Science Journalist of the Year in 2025. She teaches science writing at University College London. BEYOND BELIEF is her second, just published book. THE LIFE PROJECT was her first.

The points we covered include:

—The evolution of evidence over 8 decades, moving from rationalism, expert opinion, hunches (eminence-based) to empiricism, evidence-based

—The enormous devastating adverse impact of Dr. Spock’s Baby and Child Care book from a single sentence change, leading to an epidemic of sudden infant death...

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Joanna Stern was the Wall Street Journal technology journalist for 12 years. She’s an Emmy award winner for her documentary E-Ternal, and recently started her own company New Things, with added advice from ChatGPT!

Over the years at WSJ, I relied on Joanna’s reviews of technology for many purchases (and things I avoided) reflecting her keen and brutal assessments. I also had fun working with her on some of her video assessments of health technologies.

Her book I AM NOT A ROBOT is both hilarious and highly informative. It is a terrific primer for thos...

“You are a slightly different genetic version of yourself today from yesterday, and will be different yet again tomorrow.”—Roxanne Khamsi

“Each neuron really is a beautiful and unique snowflake”—Ed Yong

Roxanne Khamsi is one of the leading life science journalists, a contributing writer at The Atlantic, recognized with multiple awards for notable publications. Her new book is entitled BEYOND INHERITANCE. It tells the story about us all being genetic mosaics, chock full of somatic (acquired) mutations, and the implications of those mutations for our health. The myth of a single genom...

This is one of my favorite books over recent years. Sebastian Mallaby is the Paul A. Cocker Senior Fellow for International Economics at the Council of Foreign Relations and author of 6 bestselling books.

THE INFINITY MACHINE tells the story of AI’s progress over the past 15 years largely, but not exclusively, from Demis Hassabis as the protagonist and leader of DeepMind’, with its 2010 mission statement to achieve superintelligence by 2030. It’s a rich, informative, page turner.

What We Discussed:

—What is an Infinity Machine?

—Influence of Claude Shannon’s...

Dr. Trisha Pasricha is a gastroenterologist, Assistant Professor at Harvard Medical School, and the Ask a Doctor columnist for The Washington Post. Her new book gets deep into the stigmatized, taboo, rarely discussed topics of our bowel movements and farts, no less the science that backs that up, with lucid explainers for the mechanisms (such as the gut-brain axis). Her research is on the gut origin of Parkinson’s disease.

Here’s a quote from Trisha early in the book:

“I’m not a wellness guru. I’m a scientist.”

Another quote from a...

Adrian is a molecular biologist and co-founder and CEO of Genyro, a synthetic biology company. He has published 2 previous books on life science (Life Without Genes and An Intelligent Person’s Guide to Genetics). In this conversation we discussed his new book, cover below and the title of this post.

ABI. As Adrian puts it, a monumental shift, a second genesis, the “artivolution,” ability to use a molecular Gutenberg press, it’s post-Darwinian.

I made an infographic about the book and our conversation with NotebookLM

The expansion of genome sequence...

Yo-El Ju is the Barbara Burton and Reuben Morris Professor of Neurology at Washington University, St. Louis. She got her AB from Harvard and MD from Columbia and actively practices sleep medicine and is a prolific researcher, one of the top sleep scientists in the country.

Here are some of the topics we discussed and a few related hyperlinked citations:

—Importance of Deep Sleep (and her paper on what happens when deep sleep is purposely disrupted, how it is modulated, effect of alcohol

—The Orexin Antagonist drugs that promote sleep (and a study that...

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The vagus nerve, also known as the Great Nerve, connects the brain to all parts of the body, like an internet (Figure below). Every week we’re learning more about its importance for health and disease. Until recent years the brain and immune system were thought to be in separate “firewalled” compartments. But that turned out to be far from the truth.

Dr. Kevin Tracey, who directs the Feinstein Institute at Northwell Health, has been studying the vagus nerve for more than 3 decades. In the early 1990’s he made the seminal observation that stimulating the vagus re...

Back in 2005 Dan Buettner patented Blue Zones. He’s written 9 books, of which 5 were NY Times bestsellers, and has another one in the works. His 2023 Netflix documentary series “Live to 100: Secrets of the Blue Zones” won Emmy awards and was widely viewed. Many of the main points that Dan has emphasized over the years—healthy diet (he highlighted whole grains, beans, nuts, greens, and “peasant food” here), physical activity, social engagement, and sense of purpose—are backed up by randomized trials and/or large, prospective studies, as I reviewed in Super Agers.

In this interview, I asked Dan ab...

Jonathan Kipnis is a neuroscientist, the Alan A. and Edith L. Wolff Distinguished Professor of Pathology and Immunology at Washington University, St. Louis, who discovered meningeal lymphatics and has been a prolific researcher in brain drainage and the continuous immune system surveillance of the brain.

I made this infographic with the help of Notebook LM to summarize many of the concepts we discussed. (Notebook LM is free and worth trying)

We went over his new review with 24 co-author leading experts in the recent issue of Neuron

A Clever Cover

...

A recording from my enthralling conversation with Prof Matthew Cobb about the life and science contributions of Francis Crick, regarded as one of the most influential biologists of all times, along with Darwin and Mendel. As you’ll see, there’s so much more to Crick’s story than cracking DNA’s double helix structure in a matter of weeks with James Watson. Matthew Cobb, Emeritus Professor of the University of Manchester, has written several award-winning books on life science, but I think this is his most important one to date, deeply researched and a thrilling account of Crick’s life, cl...

A couple of weeks ago, the FDA Commissioner published a WSJ oped “The FDA Liberates Women’s Hormone Replacement Therapy” (←gift link) and, with other FDA colleagues, a JAMA essay entitled “Updated Labeling for Menopausal Hormone Therapy” (open-access). That change, and the data cited, led to a series of articles in the days that followed, such as at STAT News “FDA reverses decades-old warning on hormone therapy products for menopause. Agency says the treatments o!fer heart, brain, and bone health benefits” and at the Washington Post “The FDA finally corrects its error on menopause hormone therapy. Women have been ne...

Dr. Susan Monarez was the first CDC Director to be confirmed by the Senate and served from July 31, 2025 – August 27, 2025. Because she refused to give approval to new vaccine recommendations without ever seeing them or their evidence and firing scientists without cause, she was fired. In my view, she’s a hero for standing up for science and speaking truth to power.

In her first live interview since leaving the CDC, we review her background. That includes growing up in rural Wisconsin and getting her college and PhD education at UW-Madison, the latter in microbiology and immunology. She then...

Get full access to Ground Truths at erictopol.substack.com/subscribe

Get full access to Ground Truths at erictopol.substack.com/subscribe

Prof Shana Kelley is the Neena Schwartz Professor of Chemistry and Biomedical Engineering at Northwestern University and President of the CZI Chicago Biohub, which brings together life scientists at Northwestern, University of Chicago, and U. Illinois Urbana Champaign. Her lab’s website provides recent publications in the 3 major areas of biomolecular sensors, rare and single cell analysis, and intracellular molecular delivery.

You are undoubtedly familiar with wearable biosensors on the wrist and rings, and continuous glucose monitoring (CGM), all of which can transmit physiologic data in real time to your smartphone. What is different about Pr...

Thank you Bruce Lanphear, Clyde Wilson, Tracy Dennis-Tiwary, Diego Pereyra, Dr Mike Hunter, and many others for tuning into my live video with Charlotte Blease! Join me for my next live video in the app.

Whether A.I. will transform the practice of medicine in a positive way remains controversial. Health researcher Prof Charlotte Blease, on faculty at Uppsala University in Sweden and researcher at Harvard University, has written a new book —Dr. Bot—that critically assesses the unmet needs in healthcare and whether A.I. can fulfill them. She provides an optimistic viewpoint (see the subtitle), and...

Thank you Sara Garcia, Andrew O'Malley BSc PhD, Sam Hester, Julie, Stephen B. Thomas, PhD, and so many others for tuning into my live video with Peter Hotez! Join me for my next live video in the app.

Peter Hotez and I discuss his new book, co-authored with Michael Mann, SCIENCE UNDER SEIGE, on the anti-science superstorm culminating from the climate crisis, the Covid pandemic, and a vast interconnected network that has waged a direct assault on scientific truth.

During our conversation we trace history of priors in civilization, such as Lysenko and...

Thank you Jose Bolanos MD, Dr. Zeest Khan, Lawrence Toole, Julie, Stephen B. Thomas, PhD, and many others for tuning into my live video with Dr. Sanjay Gupta. Join me for my next live video in the app.

A Brief Summary of Our Conservation

We discussed the new understanding and approach to chronic pain, which affects nearly 1 in 4 adults. Dr. Gupta gets personal telling the story of his wife, Rebecca, who has an autoimmune disease and at one point he had to carry her up stairs. He also tells the story of his...

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This is a hybrid heart disease risk factor post of a podcast with Prof Bruce Lanphear on lead and a piece I was asked to write for the Washington Post on risk factors for heart disease.

First, the podcast. You may have thought the problem with lead exposure was circumscribed to children, but it’s a much bigger issue than that. I’ll concentrate on the exposure risk to adults in this interview, including the lead-estrogen hypothesis. Bruce has been working on the subject of lead exposure for more than 30 years.

Let me emphasize that the...

Eric Topol (00:06):

Hello, this is Eric Topol from Ground Truths, and I'm delighted to welcome Owen Tripp, who is a CEO of Included Health. And Owen, I'd like to start off if you would, with the story from 2016, because really what I'm interested in is patients and how to get the right doctor. So can you tell us about when you lost your hearing in your right ear back, what, nine years ago or so?

Owen Tripp (00:38):

Yeah, it's amazing to say nine years, Eric, but obviously as your...

Eric Topol (00:05):

Hello, it's Eric Topol from Ground Truths, and I've got some really exciting stuff to talk to you about today. And it's about the announcement for a new Center for pediatric CRISPR Cures. And I'm delight to introduce doctors Jennifer Doudna and Priscilla Chan. And so, first let me say this is amazing to see this thing going forward. It's an outgrowth of a New England Journal paper and monumental report on CRISPR in May. [See the below post for more context]

Let me introduce first, Dr. Doudna. Jennifer is the Li Ka...

“To navigate proof, we must reach into a thicket of errors and biases. We must confront monsters and embrace uncertainty, balancing — and rebalancing —our beliefs. We must seek out every useful fragment of data, gather every relevant tool, searching wider and climbing further. Finding the good foundations among the bad. Dodging dogma and falsehoods. Questioning. Measuring. Triangulating. Convincing. Then perhaps, just perhaps, we'll reach the truth in time.”—Adam Kucharski

My conversation with Professor Kucharski on what constitutes certainty and proof in science (and other domains), with emphasis on many of the learnings from Covid. Given the...

Thanks to so many of you who joined our live conversation with Devi Sridhar!

Professor Devi Sridhar is the Chair of Global Public Health at the University of Edinburgh. Over the past 2 decades she has become one of the world’s leading authorities and advisors for promoting global health. Her new book —How No to Die Too Soon—provides a unique outlook for extending healthspan with a global perspective admixed with many personal stories.

We talked about lifestyle factors with lessons from Japan (on diet) and the Netherlands (on physical activity), ultra-processed foods, air pollution and wa...

My conversation with Matthew Walker, PhD on faculty at UC Berkeley where he is a professor of neuroscience and psychology, the founder and director of the Center for Human Sleep Science, and has a long history of seminal contributions on sleep science and health.

Audio File (also downloadable at Apple Podcast and Spotify)

“Sleep is a non-negotiable

biological state required for the maintenance of human life . . . our needs

for sleep parallel those for air, food, and water.”—Grandner and Fernandez

Eric Topol (00:07):

Hell...

Thank you Richard DeWald, Michael Mann, Dr Avneesh Khare, Maud Pasturaud, Lower Dementia Risk, and many others for tuning into my live video with Katie Couric! Join me for my next live video in the app.

Audio File

Ground Truths can also be found on Apple Podcasts, Spotify and YouTube.

The UK is the world leader in human genomics, and laid the foundation for advancing medicine with the UK Biobank, Genomes England and now Our Future Health (w/ 5 million participants). Sir John Bell is a major force in driving and advising these and many other initiatives. After 22 years as the Regius Professor of Medicine at the University of Oxford he left in 2024 to be President of the Ellison Institute of Technology.

Professor Bell has been duly recognized in the...

Audio file, also on Apple and Spotify

Tyler Cowen, Ph.D, is the Holbert L. Harris Professor of Economics at George Mason University. He is the author of 17 books, most recently Talent.: How to Identify Energizers, Creatives, and Winners Around the World. Tyler has been recognized as one of the most influential economists of the past decade. He initiated and directs the philanthropic project Emergent Ventures, writes a blog Marginal Revolution, and a podcast Conversations With Tyler, and also writes columns for The Free Press." He is writing a new book (and perhaps his last...