Ground Truths

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. It’s a major and fascinating discovery.

Deb Cohen is an award winning investigative journalist and correspondent who trained as a physician and has worked with the BBC and BMJ. She just published BAD INFLUENCE, a book which takes us deep into the wellness-industrial complex—the confluence of the supplement, testing, tech, and pharma industries, and how they sell health anxiety to healthy people. Here are some of the points we discussed: —The big market in healthy, well people.

There has been a big shake-up in the understanding for how our brain ages. Until now, the prevailing belief was that our brain tissue shrinks with age, exemplified by the hippocampus, the region tied to memory and learning, as seen via MRI and other imaging modalities. That the microglia immune cells we were born with (embryonic) were the only types to be found in our brain. And the brain aging process was accepted to be a linear, steady deterioration.

Sarah Urbutis a physician-scientist at Harvard Medical School and the Massachusetts General Research Institute. She and her colleagues published a landmark paper in Nature on patient health journeys for 3 different cohorts—the Mass General Brigham patients, the UK Biobank, and the All of Us research program—with a cumulative 683,000 individuals, 348 diseases, and up to 52 years of follow-up. Integrating electronic medical records and polygenic risk scores (N=36).

“The future of biology is programmable.” To give you a sense of how important this topic is, Patrick Hsu is the first guest we’ve had back to Ground Truths since the podcast began a few years ago. Nearly 2 years ago we spoke about digital biology but so much has happened since to help unravel the complexities in the language of life. Patrick is a co-founder and core investigator at the Arc Institute. His work is at the intersection of biology, engineering, and AI.

This week Tony Wyss-Coray and I published an invited review paper in Nature Medicine entitled “Biological Aging Clocks in Health and Disease.” The concepts and content of the paper may be difficult to understand for people not working in life science, but they are groundbreaking and have exciting implications for the future of medicine. So this edition of Ground Truths is intended to make all of the progress comprehensible for you and to hopefully see the coming inflection point in medicine.

The tumor microenvironment (TME), composed of immune cells, fibroblasts, and endothelial cells, has emerged as critical to pathogenesis, prognosis and treatment for cancer (schematic Figure below). There’s no such thing as TMI (too much information) for TME! Yet there’s still no way of assessing it in the clinic by a blood test, and even by invasive biopsy the sampling bias for TME without broader geographic context can lead to important mistakes. That isn’t used for clinical decision making.

“I may be the expert in cancer, but you are the expert in you.”—Elisa Port, MD Ground Truths is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber.

It was just a matter of time. Agentic autonomous AI has already been applied to life science and many other domains, and today there were 2 notable publications in Nature that move this concept forward for healthcare. One is called MIRA from Jacob Kather and colleagues from Germany, and the other is called AIME, from Mike Schaekermann and colleagues at Google (acronyms defined below).

In the journal Cell, a team of >80 researchers from 4 continents reported on the discovery of a 14-protein blood test which paved the way for predicting and preventing lung cancer more than 5 years before it would be diagnosed. Current efforts in cancer are largely directed to therapy and early detection, with only a very limited foray to prevention.