Ground Truths

Ethan Mollick is an Associate Professor at Wharton, University of Pennsylvania, head of their Generative AI Lab, and author of the new book CO-EXISTENCE, just released, and on the NY Times bestseller list right away. His prior book CO-INTELLIGENCE was also huge hit, NYT bestseller. He writes ONE USEFUL THING on Substack, which is one of the most insightful and popular series of essays on AI on the platform.

Let me highlight that Ethan evaluates all of the new models independently and is not funded by any of the AI companies, which puts him in a singular or rarified group of experts.
Here are some of the topics we discussed:
* The Jagged Frontier (the term Ethan came up with that has been adopted by all)
* The end of Prompting
* The Next-Token Train
* The Bitter Lesson
* Deskilling and Never Skilling
* Hyperscaling and Recursive Self-Improvement (RSI)
* Data Centers
* Claude Table 5.2 (his new essay with a mind blowing video not to miss)
* Safety of AI and Existential Threats
* Personal AI Agents (Muse and Dot)
* Education
* Science, Authorship, Peer Review
* Medical AI—Doctors out of the loop, AI potentially better than doctors with AI
* Ethan’s use of Agents (from his new essay)

About Ground Truths

This substack has more than 217,000 subscribers from every US state and 215 countries. There are over 320,000 followers of Ground Truths so more than 100,000 folks who can easily convert to be free subscribers. If you’re one of them, please consider doing so.

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The proceeds from all voluntary paid subscriptions go to support our summer internship program. It enabled us to accept and support a record number of 62 summer interns that joined us in 2026! These are high school, college and medical students selected from thousands of applicants. We couldn’t do this expanded program without the funds coming in through Ground Truths. Thank you!

Thank you Malcolm MacPherson, Tobin Trevarthen, Rick (equity muse) Botelho, John Wills Lloyd, Arzu Najjar, and >700 others for tuning into my live video with Ethan Mollick! Join me for my next live video in the app.


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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 a different group)

—Transplant of heart from old to young and young to old (preprint) and Rejuvenation
Nature News and Views on that study by Chris Simms
And how this could markedly expand transplant donor organs
Parabiosis studies in mice

—Effect of drugs on biological aging
—slowing of biological aging with anti-fibrotic drug by proteomic clocks
—studies of semaglutide in 5 randomized trials vs placebo, organ proteomic clocks

—AI and aging biology
—Future of aging

Ground Truths has 217,000 subscribers from every US state and 214 countries. There are over 320,000 followers of Ground Truths so more than 100,000 folks who can easily convert to be free subscribers. If you’re one of them, please consider doing so.
Your subscription to these free essays and podcasts makes my work in putting them together worthwhile. If you’re not a subscriber, please join!
If you found this interesting PLEASE share it!
The proceeds from all voluntary paid subscriptions go to support our summer internship program. It enabled us to accept and support a record number of 62 summer interns that joined us in 2026! These are high school, college and medical students selected from thousands of applicants. We couldn’t do this expanded program without the funds coming in through Ground Truths. Thank you!
And big thanks to jojofinance, VivoSage, Burak Yedek, Vau Geha, José Pedro Castro, and 800 others for tuning into my live video with Vadim Gladyshev! Join me for my next live video in the app. Impressive since we had technical audio issues for the first 10 minutes and the attendees rose from 500-800!
I edited out the video/audio the first 10 minutes when we couldn’t get started so you wouldn’t have to go through the horrible echo or silence while we waited for Vadim’s return.


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

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).
His ability to talk with the silent civil servant heroes of multiple government agencies (the Blockers), members of the DOGE destruction team, and much more from the current US government administration.

Here’s a gift link to the exclusive excerpt at WSJ
I won’t review all the things we discussed here, but the chapter on the NIH reads like an Agatha Christie murder mystery. We learned a whole different version of what happened that differed from what was previously reported.

Thank you jojofinance, Andrew Bowdle, Tracy Paeschke, MD, FACC, Bob Fleischman, Sean Stevenson, and many nearly 500 others for tuning into my live video with Michael Lewis! Join me for my next live video in the app.
Ground Truths has 217,000 subscribers from every US state and 214 countries. There are over 300,000 followers of Ground Truths so more than 100,000 folks who can easily convert to be free subscribers.
Your subscription to these free essays and podcasts makes my work in putting them together worthwhile. If you’re not a subscriber, please join!
If you found this interesting PLEASE share it!
The proceeds from all voluntary paid subscriptions go to support our summer internship program. It enabled us to accept and support a record number of 62 summer interns that joined us in 2026! These are high school, college and medical students selected from thousands of applicants. We couldn’t do this expanded program without the funds coming in through Ground Truths. Thank you!



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

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.”

Or is it more complicated? Are the trial results and reasons for failure different?
I wrote a recent Ground Truths —The Coronary Artery Inflammation Controversy— on the data (what has been released to date) and my take. But I wanted to vet this with another physician-scientist who is studying atherosclerosis and turned to Prof Marios Georgakis, from the University of Munich, who as I mentioned in the previous piece, wrote a brilliant analysis of ZEUS and is also doing writing about HORIZON.
Many years ago we went through a “CV winter” when the biopharma companies largely shunned doing clinical trials for heart disease. They thought the field had been maxxed out. After a lapse of several years, there have many trials undertaken with positive results and substantial progress for better treatments vs heart disease. Both Marios and I remain optimistic that we are a long way from maxing out, as you’ll learn from the podcast. Heart disease is the number one global killer, for both men and women. That’s despite all the progress that has been made to date.

Thanks for your support of Ground Truths and to Dr. Julie Kellogg, Vau Geha, Ralph Horwitz, Jessica Coffman, Michael G. Levin, MD, and mopre than 400 others for tuning into my live video with Marios Georgakis!
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Ground Truths has 215,000 subscribers from every US state and 214 countries. There are over 310,000 followers of Ground Truths so nearly 100,000 folks who can easily convert to be free subscribers. Please consider doing that…it’s free.
Your subscription to these free essays and podcasts makes my work in putting them together worthwhile. If you’re not a subscriber, please join!
If you found this interesting PLEASE share it!
The proceeds from all voluntary paid subscriptions go to support our summer internship program. It enabled us to accept and support a record number of 62 summer interns that joined us in 2026! These are high school, college and medical students selected from thousands of applicants. We couldn’t do this expanded program without the funds coming in through Ground Truths. Thank you!



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

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/articles/s41586-026-10939-0

It’s a major and fascinating discovery. We’re talking about a “hostile takeover” of blood monocyte cells that invade the brain and ultimately completely replace the brain microglia. The problem is these new microglia are pro-inflammatory.
A surprising finding is about CHIP (blood stem cells with mutations known as clonal hematopoiesis of indeterminate potential) that was shown to be protective. It’s surprising because CHIP is common with age and until now it has been linked to bad things such as cardiovascular disease, clotting, and cancer. If this pans out, it introduces the concept of immunotherapy of the blood (“brain immunotherapy”).
We discussed recent studies of microglia replacement and ways to keep our brain microglia intact, such as prevention any breakdown of the blood brain barrier.
The role of latent viruses and the mechanism of benefit of the Shingles vaccine were touched on.
Our conversation provides far more color and perspective about why their independent, complementary, and convergent findings are so important, debunking our longstanding belief that the microglia, the immune cells in the brain, are exclusively derived from the brain. Technology driven discovery. And what are the next steps in this line of research.

I hope you found this podcast illuminating and fun. If you did, plus share it with your network. Thanks for supporting Ground Truths and your help in spreading the word.

And thank to jojofinance, Elisabetta Pilotti, Daniel Rench, Dr. Sara Wolfson, Bob Fleischman, and hundreds of others for tuning into the live video with Julia Belk and Nathan Zemke! Join me for my next live video in the app.


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