Ground Truths

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

The drainage system anatomy on influx and efflux (blue arrows)

The 3 ways the flow of glymphatics are modulated. I mentioned the recent studies that show atrial fibrillation, via reduced cardiac pulsation, has an effect on reducing glymphatic flow.

We also discussed his recent review on the immune surveillance system in Cell:

A schematic of key channels for the “faucet” and “drain”

and how the system changes from healthy to central nervous system autoimmune diseases (such as multiple sclerosis) and aging with different immune bar codes.

The outsized role of astrocytes in the brain, a subject of recent Nature feature, was also mentioned.

Our understanding of the brain’s immune system has been completely revamped. Kipnis’s recent review in Nature Immunology highlights the critical role of the outer layers —the skull, dura and meninges—as an immune reservoir that is ready to detect and react abnormalities in the brain with a continuous “intelligence report.”

Notably, Kipnis touched on lymphatic-venous anastomosis (LVA) surgery (Figure below) for Alzheimer’s disease which is popular in China, available at 30 centers in multiple cities, and the subject of multiple randomized trials as a treatment for Alzheimer’s. Trials of LVA surgery are also getting started in the United States for treatment of Alzheimer’s and Parkinson’s diseases.

Here is a Figure to show the surgical anastomoses (connections) from the deep cervical lymphatics to external jugular and internal jugular veins

This podcast was packed with insights relevant to health, spanning sleep quality, sleep medications, autoimmune diseases, and Alzheimer’s disease. I hope you find it as informative and engaging as I did.

A Poll

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This is my 4-year anniversary of writing Ground Truths. Post number 250! That’s an average of more than 1 per week, nearly 5 per month. Hard for me to believe.

Thanks to Ground Truths subscribers (approaching 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

Thank you EG, Alan, Lynn L, Stacy Mattison, Jackie, and many others for tuning into my live video with Jonathan Kipnis! Join me for my next live video in the app.

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, clearing up, as best as one can, many questions, and presenting some surprises.

The transcript is available (A.I. generated) by clicking at the top right.

A few things we discussed

—Crick’s reaction to James Watson’s book

Crick contrasted his own approach to science writing with Watson’s memoir: “The difference between my lecture and your book is that my lecture had a lot more intellectual content and nothing like so much gossip. (...) Your book on the other hand, is mainly gossip and I think it a pity in this way that there is so much of it that it obscures some of the important conclusions which can be drawn of what we did at the time”.

—The Peyote Poem, by Michael McClure (part 1) that had a big influence on Crick

—Crick’s 1994 neuroscience book “The Astonishing Hypothesis”

“You, your joys and your sorrows, your memories and your ambitions, your sense of personal identity and free Weill, are in fact no more than the behavior of a vast assembly of nerve cells and their associated molecules.”—Crick

The book has been reviewed at Science, Nature, The Economist and many other journals. Here is a gift link to The Economist It has deservedly been named a best book of 2025 by The Guardian, The Economist, and many other media.

Thank you Bruce Lanphear, Harshi Peiris, Ph.D., Elisabetta Pilotti, Allan Konopka, Stephen B. Thomas, PhD, and over 500 others for tuning into my live video with Matthew Cobb!

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Upcoming, this Wednesday 9AM PT, live podcast

I will be interviewing Dan Buettner founder of the Blue Zones

Join us!

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Thanks to US News for recently being named one of the 25 best leaders in the United States

https://www.usnews.com/news/leaders/articles/best-leaders-2025-eric-topol

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Thanks to >190,000 Ground Truths subscribers from every US state and 210 countries. Your subscription to these free essays and podcasts makes my work in putting them together worthwhile.

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.

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 needlessly scared away from effective treatments.” If you read through these links, you’ll be confused. Does MHT have proven cognitive benefits? What about a study from 1991 that showed ~50% reduction of fatal heart events with MHT? Or the 35% decreased risk of Alzheimer’s disease? Or the breast cancer increased risk attributed to medroxyprogesterone acetate?

I turned to my go-to gynecologist truth teller, Dr. Jen Gunter, to get her review of the evidence. This is a complex topic, with old data from the 2002 Women’s Heath Initiative (WHI), new reports since, population level analysis, changes in preparations of MHT including local delivery, and much more.

Here is our conversation which isn’t just about MHT but includes “Big Wellness” marketing direct to middle aged women, the new FDA approved drug for hot flashes, the $14 million cut of the NIH’s Office of Women’s Health , marked increase in philanthropic support of women’s health research, the Surgeon General nominee, ovarian failure, and a lightning round on proven benefits of MHT.

Here’s a brief clip on her views of the women’s health “wellness” predators

We also discussed the reasons for Dr. Gunter’s planned move next year back to Canada after practicing gynecology for 3 decades in the United States.

I referred to a recent GT I wrote about the WHI and the potential favorable impact of MHT on the immune system, as suggested by new data on organ clocks. That finding, which has been replicated, may be linked to healthy aging, extending healthspan.

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Thanks to the >190,000 Ground Truths subscribers from every US state and 210 countries. Your subscription to these free essays and podcasts makes my work in putting them together worthwhile.

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.Thank you Debbie Weil, Cynthia Brumfield, Sara Garcia, Harshi Peiris, Ph.D., Liane Moccia, and over 1,000 others for tuning into my live video with Dr. Jen Gunter! Join me for my next live video in the app.

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 went on to 18 years of government service with an extensive portfolio of jobs and management at BARDA, the White House, ARPA-H, and others, before becoming Acting Director of the CDC in early 2025.

We discussed the horrific CDC shooting on August 8th, days after she started. Then we reviewed a conversation that we had on August 19th in which she laid out her exciting vision for the future of CDC, emphasizing the goal of prevention (BTW, CDC stands for Centers for Disease Control and Prevention) and asked me to help as an advisor. At the time, she was well aware, with growing tension, that her tenure at CDC might be limited.

I asked about her perspective for the jobs of 4,300 people at CDC who have been terminated, which account for more than 1/3rd of the workforce, no less the gutting of the budget.

Then we got into what she learned from this ordeal and her plans for the future, which includes a very ambitious initiative: 90/90/2035. As you’ll see from our conversation, Dr. Monarez is exceptionally resilient and an optimist. She’s got lots to do in the years ahead to carry out her mission of promoting human health!

Dr. Monarez just started a Substack The Road Best Traveled so you can follow her there. It was a real privilege for me to do this interview with her. In deep admiration of her willingness to not only take on the job of CDC Director in tough circumstances, her professionalism during testimony at the Senate committee hearing, her impressive yet unrealized vision for transforming the CDC, and refusing to cave to immense pressure from the HHS Secretary to move ahead with his agenda.

Thank you Julie, Stephen B. Thomas, PhD, David Dansereau, MSPT, Dr. Sara Wolfson, Vau Geha, and >500 others for tuning into my live video with The Road Best Traveled!

Thanks for being a Ground Truths subscriber! Please spread the word.

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 Prof Kelley’s work is the ingenious way of continuously tracking any proteins in our blood via a sensor that could function just like CGM in the future (hair thin sensor applied just below the skin and data relayed to your smartphone). A proof-of-concept paper in Science showed how exquisitely sensitive such a sensor worked to track inflammation markers [interleukin-6 (IL-6) and tumor necrosis factor (TNF)] in the diabetic rat model. As seen. below, just the injection of insulin evoked inflammation, and introduction of lipopolysaccharide (LPS) did so markedly.

This capability opens up the potential for monitoring body-wide inflammation in real time, but also extends to many other conditions such as autoimmune diseases, heart failure (e.g. continuous brain natriuetic peptide monitoring), and neurodegenerative diseases (with specific markers of neuroinflammation). This innovation represents a new dimension in individualized (precision) medicine.

In our conversation, Shana takes us through the discovery of these unique bimolecular sensors that have no reagents, and use electricity to shake off the protein from DNA strands. And she maps out the path to clinical trials and commercialization in the next couple of years.

Thank you Stephen B. Thomas, PhD, Linda Kemp, Lynn L, Pat Mumby PhD, David Hobson, and many others for tuning into my live video with Shana Kelley! Join me for my next live video in the app, along with posts on biomedical news and analysis.

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Thanks you for your listening, reading and subscribing to Ground Truths.

If you found this interesting PLEASE share it!

That makes the work involved in putting these together especially worthwhile.

All content on Ground Truths—its newsletters, analyses, and podcasts, are free, open-access.

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!

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 our conversation probes whether that is justified. She has a substack, too, here

Thanks for listening to Ground Truths. Through analytic essays and podcasts, I try to cover the important issues and discoveries in life science and medicine. If you have suggestions for topics I should get into, please pass them along.

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 Stalinism in the last century. And acknowledge the future role of A.I. for promoting infinite disinformation.

Beyond human suffering and direct health outcome consequences (such as Red Covid), the toll this is taking on the career of young scientists, universities, public health agencies, and loss of public trust are reviewed. The interdependent role of the media and the wellness industry is touched on.

The book and our conversation puts forth a call to arms, potential solutions, including the need to move away from invisible scientists and political activism.

Thanks for listening to Ground Truths podcasts and reading the analytic posts.

In case you missed any, these are a few recent and related ones:

Podcasts with Michael Osterholm and Sanjay Gupta on their new books—The Big One and It Doesn’t Have to Hurt, respectively.

Next up is Charlotte Blease and her new book Dr. Bot on where we are headed with medical A.I.

If you found this interesting PLEASE share it!

That makes the work involved in putting these together especially worthwhile.

All content on Ground Truths—its newsletters, analyses, and podcasts, are free, open-access.

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.

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 mother who had a back injury and didn’t want to live because of the pain. How his family members got relief is illuminating.

Our whole understanding and approach to pain has changed, with the acronym change from RICE to MEAT.

A newly approved drug Suzetrigine (Journavx) exploits the sodium channel gene mutation initially discovered via a family of fire walkers. It’s the first new pain medicine approved for more than 2 decades. Many other new non-opioid treatments are reviewed, no less lifestyle changes (anti-inflammatory diet and sleep), and acupuncture.

Sanjay’s research over the past few years has led to a video special on CNN with the same title as the book, set to air 9 PM EST Sunday.

If you know someone suffering chronic pain, please share the post.