Ground Truths

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 those who are not fully grounded in AI getting into the history of AI and right up to date with generative AI’s progress.
To get a sense for why AI thought she was the next Tina Fey, check out the back cover! No surprise she got me laughing hard throughout the conversation, no less while reading the book.

Here is a short YouTube video she posted on her All In AI year of 2025, referred to during the podcast.
Much of her testing of >100 AI products related to medicine and health care, which is what we especially got into during our conversation. She has 3 major rules in her assessment of AI: (1) Ruthless testing; (2) Benchmark vs human; and (3) Costs, which include “compute cost” that we discussed.
Here are some of the things we covered:
* AI of her blood work
* AI of mammogram and breast ultrasound, and overall experience as a person with increased risk of breast cancer
* AI at the dentist (and ”Dentist Deep Clean”)
* Assessment of Dr. GPT
* Bill Gates on health AI
* Her AI Trainer (Chris)
* Waymo vs Uber
* Her AI Therapist (Ash)
* Nothing Bot Sex (her 2 digital lovers)
* Impact on her children (including 6 F*****g Hamsters, the robodog Sirius)

A big thanks to Ground Truths subscribers from every US state and 212 countries. 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!
Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Please don’t hesitate to post comments and give me feedback. Let me know topics that you would like to see covered.
Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. It enabled us to accept and support a record number of 51 summer interns coming 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 Tara Parker-Pope, MPH, Tracy Paeschke, MD, FACC, Chip Hughes, Bob Fleischman, Gretchen Faucett, and >400 others for tuning into my live video with Joanna Stern! Join me for my next live video in the app.



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

“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 genome, carbon copy, master blueprint, but instead a dynamic, shifting mosaic in constant internal evolution.

And here’s the back cover. I was delighted to endorse this book, and reread it to prepare for our podcast. It’s extraordinary and mind-bending.
Here are the topics we covered:
—The Math. 330 billion cells of our ~37 trillion turnover each day, which yields trillions of mutations per day.
—Cellular competition. Winners and losers of an “endoevolution,” Darwinian selection inside us whereby healthy or super-fit mutated cells can crowd out the unfit ones.
This was theorized in 1881 in a book THE STRUGGLE OF PARTS, by Wilhelm Roux
which led to Friedrich Nietzsche’s famous quote “Uniformity is pure delirium.”

—Single-cell sequencing. How this field catapulted forward owing to the ability to zoom in on genomic mutations at the cellular level.
—Cancer chemotherapy overkill. The routine scorched earth, carpet bombing approach can promote resistance and deleterious mutations, leading to an adaptive strategy of leaving some cancer cells behind, as has been shown to be effective in prostate cancer for improving survival.
—The immune system somatic hypermutation. B cells have the theoretical capacity to produce 1 quintillion unique antibodies (a million trillion). If this weren’t possible, we could die from a common cold. In the Covid pandemic, even before the Omicron variant appeared, Covid booster shots induced hundreds of unique antibodies with neutralization capacity against Omicron. The anticipatory “Red Queen” effect.
—Autocorrection of mutations. They can revert, cure a rare genetic disease from within. It can be considered “Natural Gene Therapy.” Example below of a skin condition Epidermolysis Bullosa with revertant mutations (→ normal skin appearance)
—Different role of acquired mutations through the lifespan. Examples: At embryonic stage, Lines of Blaschko (Image below). In mid-life endometriosis, and in older adults Loss of the Y chromosome (LOY) and Clonal Hematopoiesis of Indeterminate Potential (CHIP). Note these 2 somatic mutation clone conditions are associated with risk of diseases; CHIP-cardiovascular and cancer; LOY-heart failure and Alzheimer’s. I’ve written about CHIP extensively here and here.

—Phenocopy. How a somatic mutation can look the same as a germ-line, inherited mutation, with respect to a disease, and how that is determined.
—Environmental effects inducing somatic mutations: UV light, air pollution, plastics

—and 3 new papers in the past week!
* Somatic mutations in the microglia cells of the brain, same as cancer mutations, drive inflammation and are enriched in the Alzheimer’s brain
2.. The potential of “promolytic drugs” to be used to prevent cancer in people who exhibit precancerous somatic mutations
3. How somatic mutations can be the basis of autoimmune diseases

We also spoke about the role of somatic mutations in aging and super aging
A related excerpt at The Atlantic
A Quick Poll

Thank you YOUR DOCTOR KLOVER, Stephen Pribut, Elizabeth J., Maureen Susannah, Gretchen Faucett, and more than 500 others for tuning into my live video with Roxanne Khamsi! Join me for my next live video in the app.
And a big thanks to Ground Truths subscribers (> 205,000) from every US state and 212 countries. Your subscription to these free essays and podcasts makes my work in putting them together worthwhile. Please join!
If you found this interesting PLEASE share it!
Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Please don’t hesitate to post comments and give me feedback. Let me know topics that you would like to see covered.
Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. We just accepted 51 interns for the 2026 summer, a new record, from thousands of high school, college, and med school student applicants. Our fully loaded cost to do this program is ~$300,000 per year. We’re deeply appreciative for your support of Ground Truths that has enabled this program to prosper and expand.
One more thing:
SUPER AGERS was featured on the CBS Morning Show this week in a segment with Dr. Jonathan LaPook, Chief Medical Correspondent, on the meaning and measurement of biological aging.



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

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 Information Theory and Douglas Hofstadter’s Pulitzer Prize winning book Gödel, Escher, Bach
—Origin of DeepMind in 2010. Prescient. Charter, business plan, included use of agents. How Demis Hassabis was made for the mission!
—Contrasts with Sam Altman and the other AI leaders, the Oligopoly (cover of The Economist this week). For example, Nature papers vs white papers on company websites.
—In March 2016, the same day when DeepMind’s AlphaGo beat Lee Sedol, Hassabis says it’s time to do protein folding (later known as AlphaFold).
—Symbolic AI (historic, deductive, rule-based) vs Deep Learning (Toronto tribe) and Reinforcement Learning (Alberta tribe).
—The Big Miss: DeepMind’s lack of early recognition of the importance of transformer models (leading to ChatGPT), creating a big opening for OpenAI. And why was this missed? The Comeback Story. Is this happening again with coding (not in the book)?
—The AI Arms Race and Hyperscaling
—How the complex relationship between Google and DeepMind evolved
—The Double Cross
—With the dangers anticipated (parallels to Oppenheimer, Manhattan Project, and the atomic bomb), how to promote AI safety?
—Is the major build up of data centers justified?

Thank you Bob Fleischman, Jeanie, Ruben Max, FelonBroke America, Seitzinator ❌👑, and more than 600 others for tuning into our live video with Sebastian Mallaby! Join me for my next live video in the app.

And a big thanks to Ground Truths subscribers (> 200,000) from every US state and 212 countries. Your subscription to these free essays and podcasts makes my work in putting them together worthwhile. Please join!
If you found this interesting PLEASE share it!
Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Please don’t hesitate to post comments and give me feedback. Let me know topics that you would like to see covered.
Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. It enabled us to accept and support 47 summer interns in 2025! We aim to accept even more of the several thousand who will apply for summer 2026.
And, if you’re interested on extending healthspan, two recent podcasts/TV segments on SUPER AGERS
On With Kara Swisher
On PBS


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

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 Vanderbilt professor:
“An effortless, socially appropriately timed bowel movement is the second greatest bodily pleasure known to man.”

The proportion of people with bowel issues is remarkable, a brief summary:
Some of the topics covered in our lively, fun and highly informative conversation:
—The 3 P’s Propulsion, Pliability, Pelvic Floor
—Ten Myths
—99% of farts have no odor; the 1% that do are from hydrogen sulfide, Pepto-Bismol substantially reduces the latter (and an incredible experiment of people with rectal tubes and judges smelling their gas)
—What is the normal frequency of pooping?
—the Bristol Scale of poop appearance and what it means
—Transit time
—The uselessness and danger of bowel cleanses
—Fibermaxxing
—5 minutes max on the toilet and positions to help propulsion
—Psyllium and laxatives
—The art of wiping and bidets
—Fecal incontinence
—Not to miss urges and the TRPV1 and PIEZO2 receptors
—Impact of coffee, alcohol, NSAIDs (Ibuprofen, aspirin, naproxen, etc), and hydration
—What are the different definitions of constipation?
—What gives poop its color?
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Thank you YOUR DOCTOR KLOVER, Nickhil Jakatdar, Ph.D., Bob Fleischman, karemm, Jessica Nguyen, and >600 others for tuning into our live video with Trisha Pasricha! Join me for my next live video and newsletters in the app.
And a big thanks to Ground Truths subscribers (> 200,000) from every US state and 212 countries. Your subscription to these free essays and podcasts makes my work in putting them together worthwhile. Please join!
If you found this interesting PLEASE share it!
Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Please don’t hesitate to post comments and give me feedback. Let me know topics that you would like to see covered.
Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. It enabled us to accept and support 47 summer interns in 2025! We aim to accept even more of the several thousand who will apply for summer 2026.



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

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 sequences beyond “Fred’s library” (referring to Fred Sanger, father of genome sequencing, little green box)

We talked about the jump from DNA reading to editing and now writing genomes, with the potential of the latter for both good and harm. I disagreed with Adrian about the bright prospects for curing diseases, but there are many possibilities for positive impact, such as intervening vs the climate crisis and sustainability.
We also discussed the large language of life models (LLLMs) and by coincidence my colleagues and I just published a review of these in this Nature Biotechnology (←free access is hyperlinked).

“It should be possible to meet most of humanity’s needs through biologically inspired designs—to solve many global problems, revolutionize health care, extend human lifespan, and create other organisms to order.”—Adrian Woolfson
If you are into life science, I think you’ll find Adrian’s book thoughtful and provocative, even if you don’t agree with some of his optimism like a disease-free organism.
The topic connects with digital biology, a theme that is approached in many editions of Ground Truths, such as this one with Patrick Hsu
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Thank you Ric Bayly, Kevin Johnson, MD, YOUR DOCTOR KLOVER, Patricia Scott, Anne, and more than 600 others for tuning into my live video with Adrian Woolfson! Join me for my next live video in the app.
And a big thanks to Ground Truths subscribers (> 200,000) from every US state and 212 countries. Your subscription to these free essays and podcasts makes my work in putting them together worthwhile. Please join!
If you found this interesting PLEASE share it!
Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Please don’t hesitate to post comments and give me feedback. Let me know topics that you would like to see covered.
Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. It enabled us to accept and support 47 summer interns in 2025! We aim to accept even more of the several thousand who will apply for summer 2026.


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