Ground Truths

Jonathan Kipnis is a neuroscientist, the Alan A. and Edith L. Wolff Distinguished 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 NeuronA 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 veinsThis 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************************************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 2026Thank 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. Get full access to Ground Truths at erictopol.substack.com/subscribe

Matthew Cobb, Emeritus Professor at the University of Manchester and author, dives deep into the complex life of Francis Crick, a towering figure in biology. He contrasts Crick's scientific rigor with the gossip-laden memoir by Watson. The conversation explores the inspiration behind Crick's shift from physics to biology and his groundbreaking work on DNA's double helix. Cobb also discusses Crick's intriguing foray into consciousness research, his cannabis use, and the lasting impact of his ideas beyond genetics.

In this discussion, Dr. Jennifer Gunter, a leading gynecologist and women's health advocate, teams up with Eric Topol to dive into the recent FDA changes regarding menopausal hormone therapy (MHT). They tackle complex issues like the misconceptions around MHT’s cognitive benefits and the impact of various hormone delivery methods on risks. Gunter critiques the wellness industry's marketing tactics and emphasizes the need for proper research funding in women's health. Their conversation highlights the intricate balance between symptom relief and informed care.

In her first live interview since her tenure as CDC Director, Dr. Susan Monarez, a seasoned microbiologist and immunologist, shares her journey from rural Wisconsin to federal leadership. She discusses the challenges she faced during her brief term, including managing multiple outbreaks and a tragic shooting. Dr. Monarez advocates for a vision of a prevention-focused CDC and introduces her ambitious 90/90/2035 initiative to enhance home-based preventive care. Her commitment to scientific integrity shines through as she reflects on the loss of CDC staff and the importance of resilience.

Seth Berkley, a prominent physician-epidemiologist and global vaccine leader, shares insights from his book, Fair Doses. He recounts the formation of COVAX and its early challenges, including regulatory delays and vaccine nationalism. Discussion highlights include the unprecedented speed of mRNA vaccine development, the impact of vaccine hesitancy, and the importance of continuous vaccine research. Seth emphasizes the need for sustained investment in global health to ensure equitable vaccine access and prepare for future pandemics.

Tom Frieden, former CDC director and public health leader, shares insights from his book on improving health. He discusses the 'Cassandra's curse' and the 'see, believe, create' formula for addressing public health inaction. Frieden highlights strategies to combat hyperbolic discounting, making future health benefits feel immediate. He critiques wellness industry hype and emphasizes proven interventions. The conversation also explores the need for funding and data in public health, and personal changes he made to reduce toxin exposure.

In this enlightening conversation, Prof. Shana Kelley, a leader in biomolecular sensors and the President of CZI Chicago Biohub, unveils her groundbreaking work on real-time blood monitoring. She discusses a revolutionary hair-thin sensor that tracks protein levels like continuous glucose monitors. The implications for managing inflammation markers in conditions such as diabetes and autoimmune diseases are immense. Kelley also highlights the importance of AI for analyzing sensor data and multidisciplinary collaboration in advancing health technologies.

In a thought-provoking discussion, health researcher Charlotte Blease, a professor at Uppsala University and Harvard author, explores whether AI can address the unmet needs in healthcare. She tackles the potential for AI to enhance patient interaction and diagnostics while acknowledging concerns about bias and empathy. They dive into the role of AI in mental health, weighing its benefits against traditional therapy's shortcomings. Blease advocates for a balanced view on AI's advancements, addressing ethical challenges like privacy and equity.

Peter Hotez, a renowned vaccine scientist and pediatrician, explores the dire implications of anti-science sentiments alongside Eric Topol. They discuss their co-authored book which unveils a troubling nexus of the climate crisis, COVID-19, and organized misinformation. Historical parallels, such as Stalinist-era science, highlight current challenges. Hotez emphasizes the need for proactive political engagement and the crucial role of research universities in restoring public trust while advocating for effective communication in combating misinformation.

Sanjay Gupta, a renowned neurosurgeon and CNN's chief medical correspondent, shares personal insights from his life while discussing chronic pain management. He reveals his family's struggles with pain and introduces a transformative approach moving from RICE to MEAT, advocating for mobilization. Gupta highlights innovative treatments like the new drug Suzetrigine and non-opioid methods, emphasizing lifestyle changes such as diet and sleep. His compelling stories and evolving perspectives illuminate the urgent need for effective pain management solutions.