Ground Truths

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

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 shows they can reduce p-tau217 and other neuroinflammation markers
—Link of sleep regularity with less all-cause, cardiovascular, and cancer related mortality
Figure 3.9 from SUPER AGERS (SRI-sleep regularity index)
More things we discussed:
—A sleep foundation model that predicts 130 diseases
—Impact of menopause on sleep
—Getting to sleep vs staying asleep
—Role of naps
—Impact of interruptions of sleep
—Sleep apnea and new interventions
—Vagal nerve stimulation and sleep
—Cerebrospinal fluid wave that occurs during attention lapse after poor sleep
—cognitive behavioral therapy for improved sleep
—Wearables, sleep scores, and effect on sleep
—Any supplements that help sleep?
—The rare genetically endowed short sleepers

Thank you Jeoffry Gordon, MD, MPH, Dr. Sara Wolfson, Lynn L, Vau Geha, Bernie Newman, and more than 600 others for tuning into my live video with Yo-El Ju! Join me for my next live video in the app.
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Thanks to Ground Truths subscribers (> 200,000) from every US state and 210 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.
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I also want to thank the National Academies of Science, Medicine and Engineering for their recent recognition.



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

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