STEM-Talk

Today we have Dr. Marina Walther-Antonio, a Mayo Clinic researcher who investigates the role of the microbiome in cancer and reproductive health, particularly endometrial and ovarian cancers. According to the World Cancer Research Fund International, endometrial and ovarian cancers are among the top 10 most prevalent cancers in women worldwide, and there are still no standard screenings for early detection. Marina is an assistant professor in the Department of Surgery and the Mayo Clinic Center for Individualized Medicine Microbiome Program. She has a joint appointment in the department of Obstetrics and Gynecology. Today we talk to Marina about how she and her colleagues are utilizing the methodologies of environmental microbiology and technologies used in astrobiology to improve our understanding of endometrial and ovarian cancers. Through her investigations into the microbiome, she and her team are developing early detection tests that will enable clinical interventions before certain cancers develop. Show notes: [00:03:13] Dawn opens our interview asking Marina about the history of her interest in extraterrestrial life. [00:05:49] Dawn mentions that Marina did her undergraduate studies in Portugal at the University of Aveiro, where she majored in biology. Dawn asks why Marina chose biology as her major. [00:06:39] Ken explains that the undergraduate programs at Aveiro University require students to do a year of research outside the university and asks Marina about her experience with this requirement. [00:08:34] Ken explains that while Marina was conducting her internship at NASA Ames Research Center, there were several projects under way at the astrobiology institute, with the one that Marina was assigned to looking at a Mars analogue site in Oregon’s Warner Valley. Ken asks what kind of work Marina did on this project. [00:10:06] Ken asks Marina why after earning a master’s degree in microbiology from Indiana University, she went to Washington State University to earn a Ph.D. in environmental sciences. [00:13:29] Dawn asks about Marina’s Ph.D. research on microbialites, which are microbial structures that can thrive at the bottom of certain freshwater lakes and other extreme environments. [00:16:02] Dawn explains that just as Marina began researching microbial populations, the Mayo Clinic Center for Individualized Medicine created a microbiome program. Dawn asks Marina about the circumstances that led to her joining Mayo. [00:19:05] Dawn mentions that Dr. Claire Fraser, the director of Maryland’s Institute for Genome Sciences pointed out in Episode 32 of STEM-Talk that there are more microbes on a single person’s hands than there are people on Earth, as well as the fact that our gut is home to more than 100 trillion bacteria. Dawn asks Marina to talk about this microbial side of humanity. [00:21:51] Ken mentions that if listeners are interested in learning more about the microbiome and how it affects human health, they should listen to Episodes 20 and 168 with Dr. Alessio Fasano. Ken asks Marina to give a short overview of the microbiome. [00:25:37] Dawn asks Marina how the focus of her research shifted to the role of the microbiome in cancer and reproductive health. [00:29:00] Dawn explains that endometrial and ovarian cancers are among the top 10 most prevalent cancers in women worldwide; with ovarian cancer being the most common gynecological malignancy and the fifth leading cause of death due to cancer in women in the nation. Dawn goes on to explain that in a 2023 paper Marina investigated the area of microbiome that is associated with ovarian cancer to better understand the microbiome’s potential in early detection. Dawn asks Marina to talk about this study and its findings. [00:35:55] Given the small scale and sample size of her initial study, Ken asks Marina what her ideal follow-up study would look like. [00:38:37] Ken mentions that in 2019 Marina published the results of a study that found that post-menopause is a key factor in the composition of endometrial cancer microbiome. This study also investigated the impact of patient factors on the microbiome, including menopausal status, BMI, and vaginal pH balance. Ken asks Marina to elaborate on the findings. [00:44:13] Dawn notes that there is no standard screening for early detection of ovarian and endometrial cancers despite their prevalence worldwide. Dawn asks Marina about the work she and her colleagues are engaged in in this space. [00:47:17] Dawn explains that prior to Marina’s aforementioned study, vaginal pH had not been associated as a risk factor in endometrial cancer. Dawn goes on to explain that variations in microbial compositions are implicated in a number of gynecologic and obstetric diseases. Marina’s core question was that since the vaginal microbiome is so crucial to women’s health, why then do vaginal microbial profiles vary strikingly from person to person. This question, as Dawn explains, led to a study and 2020 paper titled “Daily Vaginal Microbiota Fluctuations Associated with Natural Hormonal Cycle, Contraceptives, Diet, and Exercise.” Dawn asks Marina to talk about this study. [00:54:23] Ken asks Marina about her finding that exogenous hormones in contraceptives may affect vaginal microbiota. [00:56:42] Dawn asks Marina about future research that will stem from her study. [01:00:29] Dawn asks Marina about her job as director of Mayo’s mentorship and Ph.D. program, and her passion for mentorship. [01:05:24] Given her accomplished and varied career, Ken asks Marina what advice she has for young people beginning their careers in science. [01:10:06] Circling back to Marina’s original interest in the search for extraterrestrial life, Ken explains that among the NASA scientists we’ve had on STEM-Talk there is disagreement on our chances of discovering intelligent life. While our guest Ed Wiler is confident that we will be able to prove the existence of life off earth within the next 20-30 years, Pascal Lee says he doesn’t think it is likely that we will discover intelligent or complex life anytime soon. Ken asks Marina to weigh in on the matter. Links: Marina Walther-Antonio Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio

Today Ken interviews his co-host Dr. Dawn Kernagis about her new position as the Director of Scientific Research for DEEP, a UK startup that is pioneering a new era of ocean exploration. For listeners unfamiliar with Dawn’s background, she is a NASA-trained NEEMO Aquanaut, a Fellow of the Explorer's Club Fellow and has been inducted into the Women Divers Hall of Fame. In addition to co-hosting STEM-Talk for the past nine years, Dawn is also a Visiting Research Scientist at IHMC. Dawn’s research over the years has been focused on protecting the brain and nervous system of people working in extreme environments. Prior to joining IHMC, Dawn completed her Ph.D. and Postdoctoral training at Duke University, where she studied the genetics of decompression sickness and mechanisms of oxygen toxicity in divers. In today’s interview, Dawn talks about DEEP’s mission to create subsea stations that will allow humans to live and work permanently underwater. Show notes: [00:03:20] Ken reminds listeners of Dawn’s first STEM-Talk appearance as a guest on Episode 19 where she conducted the interview from the bottom of the ocean floor while she was a member of NASA’s NEEMO Mission 21. [00:04:13] Ken asks Dawn what she was like as a child. [00:05:48] When Ken asks Dawn what she was like as a child, she talks about how she was an annoying kid because she was always asking people questions like, “Why is the sky blue?” [00:06:49] Dawn talks about the different places she lived during her childhood. [00:07:34] Ken mentions that Dawn was inducted into the Women’s Divers Hall of Fame. He asks her how old she was when she first became interested in diving. [00:10:35] Dawn talks about how she wanted to attend the University of North Carolina after high school but ended up at North Carolina State University and then Duke University. [00:12:18] Ken asks Dawn to elaborate on her decision to change her field of study multiple times throughout her collegiate career. What follows is an interesting conversation about the importance of a person following their passion. [00:14:53] Dawn talks about cave diving and how she and her friends used to do deep dives of six and seven hours at a time. Dawn explains how this led to her obsession with ways to protect people who dive into extreme underwater environments. [00:18:28] Ken asks Dawn how she learned that some people have a genetic predisposition to decompression sickness. [00:21:32] The conversation shifts to Dawn’s Ph.D. journey and how Richard Moon, who was a STEM-Talk guest on episode 26, played a significant role in her development. [00:26:14] Ken and Dawn reminisce on the practice of performing academic research in libraries. [00:28:20] Ken points out that despite Dawn’s extensive experience in human physiology with respect to diving, her doctoral work focused on cancer-related research. He asks her to talk about that seemingly odd combination. [00:34:10] Dawn talks about two papers that emerged from this research. One paper addressed how genes with bimodal expression patterns not only define clinically relevant molecular subtypes of ovarian carcinoma, but also provide ideal targets for translation into the clinical laboratory. The other paper looked at precise microarray-based predictions of tumor behavior in breast cancer patients. [00:39:00] Ken asks Dawn to recount the story of how the two of them met. [00:41:52] Ken asks Dawn to discuss the paper she co-wrote with Dom D’Agostino on mitochondrial health and its relationship to potentially preventing oxygen toxicity during exposure to hyperbaric environments. Dawn goes on to talk about some of her other IHMC-related research. [00:43:22] Ken asks Dawn to discuss her acceptance into the Aquanaut Program and her participation during one of NASA’s NEEMO missions. [00:46:04] Ken asks Dawn to reflect on her time on NEEMO Mission 21, and if there are any key takeaways she can discuss. [00:49:04] Ken asks Dawn to describe saturation diving, the research involved, and the health implications on saturation divers that are not present in other forms of underwater exploration. [00:52:04] The conversation shifts to how Dawn became the Director of Scientific Research for DEEP, a UK startup that aims to “Make Humans Aquatic.” [00:55:02] Ken explains that DEEP is a company that is pioneering a new era of ocean exploration and asks Dawn to give a primer on the importance of better understanding the Earth’s oceans. [00:56:12] Ken mentions DEEP’s mission to expand human subsea habitation through research and innovation. Dawn explains some of the challenges associated with constructing underwater habitats. [00:57:36] Ken asks about DEEP’s goal to create a relatively permanent deep-sea human habitat, analogous to the International Space Station. Called the Sentinel System, the underwater habitat will serve as a place for researchers to live and work. [01:01:23] Ken explains that the Sentinel System will operate at a depth of up to 200 meters, which represents the epipelagic zone, or sunlight zone, which is the deepest point where light penetrates the ocean. To put this in perspective, the average depth of the ocean is 3,688 meters. Ken asks Dawn to talk about how little we actually know about what exists below the 200-meter depth of the epipelagic zone. [01:02:58] Ken mentions that NASA has a long history of using the sea as a loose analogue for space. With renewed interest in human space exploration of the Moon and Mars, Ken asks if the Sentinel System will help in the preparation for deep space missions. [01:05:10] Ken asks Dawn to discuss what other areas of research she is excited to explore once the Sentinel System is fully operational and in the water, including a project that involves IHMC. [01:06:50] Dawn gives an overview of  DEEP’s current testing and training facility, which  is located in the UK. [01:07:55] Ken asks Dawn to talk about DEEP’s increased presence in the United States and Florida, including a project with the Florida Institute of Oceanography. [01:08:47] Ken asks Dawn about an anonymous billionaire who is funding DEEP. [01:10:06] Ken asks Dawn about her responsibility of establishing DEEP’s first U.S. office in Raleigh, N.C. [01.11.03] Dawn ends the interview talking about how much she loves the work that she does. Links: Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio

Today we have Dr. Mari Dezawa, one of the world’s leaders in stem-cell research and regenerative medicine. Mari is a pioneer in this emerging field and is known worldwide for her discovery of MUSE cells, a unique type of stem cell with exciting clinical potential. MUSE is short for Multilineage-Differentiating Stress-Enduring Cells. The discovery of the MUSE cell in humans has many biological and medical implications, and the human body may have a greater regenerative potential than we might have ever imagined. In collaboration with major national and international institutions, Mari and her colleagues are promoting research on MUSE cell-based regenerative medicine for diseases without definitive treatments. She and her team are also exploring the differences in regenerative capacity between less and more complex animals from the viewpoint of the stem-cell system. Mari is a professor and chair of the Division of Stem Cell Biology and Histology at Tohoku University School of Medicine. She has published more than 200 papers and is particularly known for her 2010 paper on the mechanisms of MUSE cells. In 2018, she was appointed a fellow of the U.S. National Academy of Inventors and has been the recipient of numerous awards, including the Japanese Government’s Prize for the Commendation for Science and Technology. Show notes: [00:04:10] Ken opens the interview by mentioning that although Mari was born in Japan, her family moved to the U.S. when she was only eight months old. Ken asks if it is true that Mari finds it difficult to answer the question of where her hometown is. [00:05:23] Ken asks Mari how she handled moving so much as a child. [00:05:52] Ken mentions that Mari’s father was a researcher and asks when she became passionate about research and science. [00:06:58] Ken mentions that Mari attended the Chiba University School of Medicine and asks what inspired her to go to medical school. [00:07:19] Ken explains that after Mari earned her medical degree, she attended Chiba University Graduate School of Medicine for her Ph.D. Ken mentions that while Mari was initially a cardiology resident, she later decided to focus on clinical research and became a stem-cell researcher. Ken asks what led her to shift from cardiology to stem-cell research. [00:08:25] Ken explains that Mari is well-known for her research into the role of stem cells in regeneration and functional recovery of nerve and muscle cells. Ken asks how and when she first became interested in stem cells. [00:09:56] Ken asks Mari to give a brief overview of stem cells and their significance. [00:11:18] Ken mentions that Mari remained at Chiba University as a research associate after earning her Ph.D in 1995. She then took a position as an associate professor at Yokohama City University Graduate School of Medicine before accepting a position at Kyoto University Graduate School of Medicine as an associate professor in 2003. Ken explains that while at Kyoto, Mari developed methods to induce bone marrow stromal cells to generate neuro and skeletal muscle cells, which play a crucial role in tissue repair and regeneration and are widely studied for their potential to serve as therapeutic agents. Ken asks Mari to give a quick primer on the crucial role these cells play in tissue repair. [00:13:25] Ken explains that in 2003, a member of Mari’s technical staff at Kyoto asked her whether they should discard some cultured adult rat and human bone marrow mesenchymal stem cells (MSCs) after she had noticed several strange cell clusters. Ken asks Mari to share what happened next and how this set her on the path to the discovery of Multilineage-Differentiating Stress-Enduring Cells. [00:16:03] Ken asks Mari to elaborate on this story and explain how a mistake led to this incredible discovery. [00:20:48] Ken explains that in 2008 Mari became professor and chair of the Department of Stem Cell Biology and Histology at Tohoku University Graduate School of Medicine. Then in 2010 she published a paper on the results of her investigations into MUSE cells. Ken asks about this paper and why it was so significant. [00:25:11] Ken mentions that one of the key characteristics of MUSE cells is their ability to repair organ tissues, and their ability to repair themselves quickly. Ken asks Mari to explain the significance of MUSE cell resilience and self-repair. [00:26:30] Ken asks Mari how MUSE cells are collected. [00:28:26] Ken asks Mari about her 2018 paper that looked at the use of MUSE cells in the treatment of acute myocardial infarction. [00:31:03] Ken explains that stem cells go through cytokine differentiation, a process that can often take several weeks or more to complete. However, Mari uncovered that a simple mechanism could substantially shorten this timeframe, which she reported on in a 2022 paper, titled “Phagocytosing Differentiated Cell-Fragments is a Novel Mechanism for Controlling Somatic Stem Cell Differentiation Within a Short Timeframe.” Ken asks Mari to discuss this paper and its findings [00:33:51] Ken asks Mari if she sees any potential military applications for MUSE cells. [00:35:16] Mari explains what exosomes are and how they might be applied in the context of MUSE cells. [00:36:14] Ken mentions Mari’s report on nasal administration of stem cells titled “Nose-to-Brain Delivery of Human Cells Enhances Structural and Functional Recovery in the Murine Ischemic Stroke Model.” Ken asks Mari to talk about the findings in this paper. [00:37:34] Ken asks Mari about her paper in development on the use of MUSE cells in the treatment of traumatic brain injury and dementia. [00:38:54] Ken brings up the issues with models of Alzheimer’s not tending to reflect the reality of the disease in humans and asks Mari what her plans are for applying her research to human trials in Alzheimer’s. [00:40:21] Ken asks Mari for her thoughts on the use of MSCs and MUSE cells for health span optimization. [00:42:11] Ken explains that in addition to her university work, Mari also works with a company called MUSE Cell Innovations, which is looking to revolutionize regenerative medicine and longevity through advancements in cellular science. For full disclosure, Ken explains that both he and Mari serve on the scientific advisory board of MUSE Cell Innovations. Ken asks Mari to talk about her work there. [00:44:13] Ken mentions that in another interview, Mari talked about how her hobbies were a way of balancing her life and career. However, Mari never explained what those hobbies were, so Ken asks her to elaborate. Links:   Mari Dezawa bio MUSE Cell Innovations Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page

Today we have our good friend and colleague Dr. Andrew Koutnik on the show. Andrew is a research scientist who studies the influence of nutrition and metabolism on health, disease and performance. He specializes in Type 1 diabetes and works with a wide range of people to improve their metabolic health and athletic performance. Andrew is a visiting research scientist at IHMC and has worked with Harvard, Johns Hopkins, NASA, and the Department of Defense to develop evidence-based strategies for overcoming complex health challenges. He is a graduate of Florida State University and earned his Ph.D. in medical sciences at the University of South Florida, where he worked with another good friend of ours, Dr. Dominic D’Agostino, who has been a previous STEM-Talk guest. Show notes: [00:02:50] Dawn welcomes Andrew to the show and asks him about his website, andrewkoutnik.com, the quote on the site’s homepage “Demystifying complex science to help you thrive in your health journey,” and the tagline “Challenging the status quo of metabolic health, human performance, and the management of type1 diabetes.” [00:05:31] Ken asks Andrew how old he was when he first learned he had Type 1 diabetes. [00:08:32] Dawn asks why Andrew believes his Type 1 diabetes is one of his life’s ultimate assets? [00:12:51] Ken mentions that Andrew grew up in Tallahassee and that despite suffering from childhood obesity, he was relatively athletic as a child. Ken asks Andrew to talk about his childhood. [00:14:20] Dawn asks Andrew to talk about the weight-loss journey he underwent as a teenager. [00:17:25] Dawn shifts gears to ask Andrew about how he got into science, mentioning that when he was younger, he never saw himself becoming a scientist. [00:20:19] Dawn asks if it is true that Andrew was the sort of kid who would constantly asked questions. [00:22:11] Dawn asks Andrew if it is true that after enrolling at Tallahassee Community College, it took him a while to decide on his major. [00:22:58] Ken asks Andrew to talk about the impact that his undergraduate anatomy and physiology class and professor had on his journey. [00:24:44] Ken mentions that after graduating from FSU, Andrew went to the University of South Florida where he worked with Dominic D’Agostino, who is both a previous STEM-Talk guest and a current colleague of Andrew’s. Ken asks Andrew how he met Dom. [00:27:46] Dawn asks Andrew how he came to work in Dom’s lab. [00:29:00] Dawn asks Andrew if his wife is still in touch with her former roommate, who connected Andrew and Dom. [00:29:21] Ken asks Andrew to touch on some of the research he did with Dom while he was pursuing his Ph.D. [00:31:49] Dawn shifts gears to talk about Andrew’s work in metabolic health and Type 1 diabetes. Dawn explains that a study published by the University of North Carolina found only 12 percent of Americans were metabolically healthy. Additionally, researchers from the Friedman School of Nutrition Science and Policy at Tufts University found in 2022 that only 6.8 percent of Americans had good cardiometabolic health. Dawn asks Andrew how he works with people who want to improve their metabolic health. [00:34:19] Ken asks Andrew for his thoughts on the sentiment that a ketogenic diet is hard to sustain. [00:36:55] Ken mentions that  Andrew was part of a review that looked at carbohydrate restriction for diabetes, which is a practice that had been in use since the 1700s. It fell out of favor once insulin was discovered in the 1920s. Ken goes on to explain that carbohydrate restrictive diets, like the ketogenic diet, have regained popularity for the treatment and management of diabetes, weight-loss and a range of other health issues such as migraines, cancer and depression. Ken asks Andrew to first explain the history of carb-restrictive diets as a treatment of diabetes. [00:39:43] Ken asks Andrew to talk more about the aforementioned 2021 review and its argument in favor of a medical nutrition therapy for diabetes management. [00:47:21] Dawn quotes a passage from the American Diabetes Association website that reads, “Before insulin was discovered in 1921, people with diabetes didn’t live for long. There wasn’t much doctors could do for them. The most effective treatment was to put patients with diabetes on very strict diets with minimal carbohydrate intake. This could buy patients a few extra years but couldn’t save them. Harsh diets, some prescribed as little as 450 calories a day, sometimes caused patients to die of starvation.” Dawn asks Andrew if he feels that this quote discourages the use of carb-restriction and medical nutrition therapy for diabetes management. [00:49:22] Dawn asks Andrew how the treatment of diabetes went from the use of insulin being prescribed along with carbohydrate restriction, to purely pharmacological interventions. [00:50:59] Dawn asks Andrew to talk about the significance of the fact that carbohydrates are the only macronutrient directly digested into glucose, making carbs the main determinant of postprandial glycemia and insulin requirements, which creates a mismatch between insulin kinetics and glucose. [00:55:29] Ken pivots to talk about the work of Jeff Volek at Ohio State University, one of the founders of Virta health, and our guest on STEM-Talk episodes 43, and 149. Ken goes on to explain that Virta offers nutrition-based approaches to losing weight and reversing diabetes. Virta has an impressive track record of success with Type 2 diabetes. The average weight loss for those using Virta’s system is 31 pounds, and enrollees reduced their medications by 63 percent. Ken asks Andrew why these are such impressive achievements. [00:57:07] Dawn asks Andrew about the concerns people have about low carbohydrate diets for diabetes. [01:00:24] Dawn asks, given that total medical costs for diabetes in the US is approaching a billion dollars a day, if Andrew could discuss how research into medical nutrition therapy for diabetes should become a priority. [01:02:44] Dawn pivots to talk about Andrew’s work in optimizing human performance, mentioning that he recently put out an article on Substack titled “Revolutionizing Sports Nutrition: New Insights on Low-Carb vs High-Carb Diets in Strenuous Exercise Performance.” Dawn explains that this article was based on a study Andrew and his colleagues published challenging the conventional thinking that carbohydrates were essential to athletic performance. Dawn asks Andrew to talk about the origins of the conventional wisdom that carb-loading is essential for athletic performance. [01:06:21] Ken asks Andrew to talk about the physiology behind the potential of low-carb diets to improve athletic performance in certain contexts. [01:08:47] Dawn asks Andrew to give an overview of his 2023 paper titled: “Low and High Carbohydrate Isocaloric Diets on Performance Fat Oxidation, Glucose and Cardiometabolic Health in Middle-Aged Males.” [01:13:41] Ken comments on how active, athletic and outwardly healthy-looking people being prediabetic is likely more common than people think. [01:15:35] Ken comments that this incidence of prediabetes in athletes appears to be most common in endurance athletes. [01:17:04] Ken explains that Andrew released a study earlier this year looking at the performance of triathletes who are adapted to very low-carb diets, as well as very high-carb diets. Ken goes on to explain that this study examined the belief that very low-carb diets would impair prolonged performance during strenuous exercise. Ken asks Andrew to explain the design of this study. [01:20:27] Ken explains that the aforementioned study produced three key findings, which he asks Andrew to walk listeners through. [01:23:48] Dawn notes that the ketogenic diet has become more popular in recent years, and that in response one can see numerous “keto-friendly” versions of typically high-carb foods, like breads and ice creams. Dawn asks Andrew what his take is on such products. [01:27:50] Ken asks Andrew if it is true that he has some interesting research findings coming down the pipeline soon. [01:28:36] Dawn wraps up our interview by asking Andrew if it’s true that he taken up jujitsu. Links: Andrew Koutnik bio Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio

It’s time for another episode of Ask Me Anything. Dawn and Ken answer listener questions that range from generative AI to whether grip strength is a biomarker for longevity and the potential of ketamine as a treatment for depression. Dawn also gives a brief overview of work she is doing with the deep-sea technology company Deep. As a special treat at the end of today’s episode, Dawn plays a recording of the commencement speech that Ken recently gave at the University of West Florida. As the saying goes, you don’t want to miss it. Show notes: [00:02:18] Ken starts off the episode with a listener question about whether Dawn and Ken read print books or digital, the reason being that a listener recently came across an article that claimed digital screens are rewiring our brains. [00:05:32] A listener asks about a paper titled “Grip Strength An Indispensable Biomarker for Older Adults” which claims that the ability to hang from a bar for 60 seconds for men, and 30 seconds for women, indicates that a person is likely to live longer. The paper claims that a decline in grip strength is associated with adverse health consequences, and the listener asks Ken what advice he has for developing and maintaining grip strength. [00:10:20] A listener asks a question inspired by our recent interview with Dr. Frank Butler. The listener asks if Ken has heard about the FDA approved depression therapy, esketamine, which is a derivative of ketamine and is a long-standing therapy for depression. [00:12:37] A listener asks Ken about a 2023 paper in the journal Age and Aging titled “Higher Dietary Protein Intake is Associated with Sarcopenia in Older British Twins” [00:16:13] A listener asks Ken about “Whisper,” which is a transcription product from OpenAI. The listener explains that OpenAI disclaims that Whisper should not be used in high-risk domains. However, according to a story by the Associated Press titled “Researchers Say an AI Powered Transcription Tool Used in Hospitals Invents Things No One Ever Said,” medical centers have already begun to use the tool to transcribe physician consultations. The listener explains that, according to the article, the use of Whisper in these contexts has led to numerous ‘hallucinations’ from the AI tool and the listener asks Ken what his thoughts are on how tools like Whisper should be integrated into various industries. [00:20:21] A listener asks for Ken’s thoughts on a series of articles by Kevin Roose in The New York Times claiming that there is no reason to learn how to code and program because very soon AI will take over all coding. Mr. Roose also asserts that the time is soon approaching when we need to have discussions on what rights to grant sentient AI. [00:21:57] A listener asks Ken if he concurs with a report from the National Academy of Medicine titled “Generative Artificial Intelligence in Health and Medicine – Opportunities and Responsibilities for Transformative Innovation,” which notes that large language models (LLMs) hold huge promise for patient care and healthcare system workflows, as well as risks. The listener asks if Ken agrees with the report’s claims that two areas in which we could see near term applications of LLMs are patient education and synthesis of information of electronic medical records. [00:23:35] As a follow up question, Ken is asked about the aforementioned report’s discussion of the “digital twin” concept. A digital twin is a computational representation of a patient or disease that could be used to speed up virtual experiments or subgroup analysis of investigational agents that carry risk for real patients. [00:26:26] A listener asks for Ken’s thoughts on a paper published in the journal of Nutrition Health and Aging titled “Effects of Vitamin D3 Omega 3 Fatty Acids and a Simple Home Exercise Program on Change in Physical Activity Among Generally Healthy and Active Older Adults.” The paper claims that among generally healthy, active and vitamin D3 replete individuals 73 and older, that Vitamin D supplementation had a detrimental effect on physical function and activity. [00:28:32] A listener asks Ken and Dawn what their take is on the term “settled science” and if it is ever appropriate to call some science “settled.” [00:30:06] A listener asks both Ken and Dawn whether they have a favorite healthy snack. [00:31:31] A listener asks Ken about his blood flow restriction training and what devices he uses for these workouts. [00:32:29] A listener asks about a new sub-sea technology company called Deep, which Dawn works with. [00:34:21] Dawn wraps up the episode mentioning that a little birdie told her that Ken recently gave a good commencement address to the graduating class of 2025 at the University of West Florida. Dawn then plays the audio from Ken’s speech. Links: Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio

Today we have Dr. Michael A. Schmidt, the founder, CEO, and Chief Scientific Officer of Sovaris Aerospace, a company focused on assessments and solutions applied to humans in space and extreme environments on Earth.  Michael is also a professor of aerospace medicine at the University of Central Florida College of Medicine, one of the few programs in the U.S. that offers a medical residency in aerospace medicine. Michael is known for his work pioneering the field of precision medicine. He uses molecular analytics, coupled with physiologic and behavioral assessments, to facilitate human performance and resilience on Earth as well as in the extreme environment of space. His work covers a spectrum from NASA, the NFL, the NBA, U.S. Olympic teams, Nike, SpaceX, Axiom Space, NASCAR, Special Operations, the Naval Submarine Medical Research Lab, the Mayo Clinic, and others. We had a long and fascinating conversation with Michael and decided to break the interview into two parts. This episode focuses on Michael’s background and the cognitive and physical challenges astronauts experience in spaceflight. We also dive into the many ways that precision medicine is facilitating human performance and resilience here on Earth. In part two of our conversation, Michael talks about his work with NASA and SpaceX on the challenges of civilian spaceflight and the future of Mars exploration, including the construction of permanent colonies on the Moon and Mars. You won’t want to miss that conversation. Show notes: [00:03:59] Dawn opens our interview mentioning that Michael grew up in Minnesota in a small farming community, asking if it’s true that he sometimes had to do chores in 20- to 30-degree weather. [00:06:50] Dawn asks if it is true that Michael fell in love with science at a young age, even building telescopes at the age of 11. [00:08:00] Dawn asks Michael what it was that led him to become so fascinated with space specifically. [00:08:58] Dawn asks if Michael ever thought about becoming an astronaut. [00:10:09] Ken asks if it is true that Michael was a big reader as a child. [00:11:21] Dawn asks Michael to talk about his childhood athletic interests. [00:11:55] Dawn asks how it was that a high school quarterback from a small town in Minnesota ended up at university in the United Kingdom. [00:13:38] Ken asks Michael what years he worked at NASA Ames Research Center. [00:14:51] Ken mentions that when Michael was at NASA Ames, he did work collecting molecular and physiologic assessments of humans using NASA’s 20-G centrifuge. Ken asks Michael to talk about the centrifuge and how he used it in his studies of hypergravity. [00:17:49] Ken comments on the fact that pieces of equipment like NASA’s 20-G centrifuge are a precious scientific resource, and when they cease functioning, unfortunately, they are unlikely to be replaced. [00:19:40] Ken and Michael discuss the fact that microgravity, despite being one of the most pressing effects on astronaut health, is the one of the least addressed problems in human spaceflight. [00:21:48] Ken explains that Michael is the founder, CEO and Chief Scientific Officer of a company called Sovaris Aerospace, which is focused on assessments and solutions applied to humans in space and extreme environments on Earth. Ken asks Michael where the idea came from to found this company. [00:24:35] Dawn explains that since the human genome was first sequenced, there has been an acceleration of genome-based technologies that have made it possible to consider a person’s genetic makeup, both in healthcare and optimizing performance. Dawn asks Michael to talk about the work he does applying genomics to human spaceflight. [00:28:52] Dawn asks about Michael’s direction of the molecular profiling and precision medicine efforts for the Golden State Warriors during their record-breaking 73-9 season [00:32:57] Dawn mentions that Michael published a review in the journal Metabolomics in 2013 that looked at the use of omics-based analyses and their potential to enhance astronaut safety and performance. Dawn goes on to say that omics allows us to identify differences in humans responsible for different responses to extreme conditions. Dawn asks Michael to talk about this review and what he learned in terms of the risk profile of individual astronauts and how personalized medicine could mitigate some of the risks. [00:42:01] Ken circles back to the heterogeneity of responses to exercise in space, a phenomenon that is seen on Earth as well. Ken notes that while large populations of astronauts don’t yet exist to be studied, large populations and their response to exercise can be studied on Earth, such as Marcas Bamman’s current NIH-funded multicenter exercise study with aging populations here at IHMC. Here Michael talks about his work creating “digital twins” of astronauts to model exposure to extreme environments on personalized digital models of astronauts. [00:46:04] Ken mentions that the difference between digital twin models in engineering and digital twins used in biomedicine is that engineered systems are nearly fully understood and can therefore be modeled with great accuracy and completeness, while there is much more unknown in biological systems. [00:48:15] Ken asks Michael, given all the confounds and environmental stressors in spaceflight, how confident can we be that omics analyses performed on Earth will provide useful insights about performance in space. [00:54:13] Dawn pivots to discuss Michael’s work as president of the Human Research Program for Civilian Space Flight, the purpose of which is to address the widespread needs that civilians will face as space travelers. [01:01:03] Ken shifts gears to ask Michael to talk about the specific cognitive and physical challenges that humans will face in long duration spaceflight, such as a flight to Mars. [01:10:05] Ken mentions that APOE4/4 positive patients see increased risk of cognitive decline from therapeutic radiation on Earth. Ken notes that while therapeutic radiation is different from the radiation experienced by astronauts, this still poses worrying prospects for APOE4/4 positive astronauts. [01:11:28] Ken and Michael discuss the importance of developing both biological and engineering countermeasures to hazardous exposure to astronauts in space. Links: Michael Schmidt bio Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio

Our guest today is Dr. Ken Forbus, the Walter P. Murphy Professor of Computer Science and a Professor of Education at Northwestern University. Joining Dr. Ken Ford to co-host today’s interview is Dr. James Allen, who was IHMC’s associate director until he retired a few years ago. James is a founding fellow of the American Association for Artificial Intelligence and a perfect fit for today’s discussion with Dr. Forbus, who, like James, is an AI pioneer.  Back in 2022, James was named a fellow by the Association for Computational Linguistics, an organization that studies computational language processing, another field he helped pioneer. Dr. Forbus also is a Fellow of the Association for the Advancement of Artificial Intelligence and was the inaugural winner of the Herbet A. Simon Prize for Advances in Cognitive Systems. He is well-known for his development of the Structure Mapping Engine. In artificial intelligence and cognitive science, the Structure Mapping Engine is a computer simulation of analogy and similarity comparisons that helped pave the way for computers to reason more like humans. Show Notes: [00:03:07] Ken opens the interview with Dr. Forbus by asking if it is true that he had an unusual hobby for a nerdy kid growing up. [00:04:18] James mentions that Dr. Forbus’ family moved often when he was younger and asks how that affected him. [00:05:18] Ken mentions that when Dr. Forbus was in high school, he filled his free time reading about psychology and cognition before eventually coming across some articles on AI. Ken asks Dr. Forbus to talk about this experience and what happened next. [00:07:49] James asks Dr. Forbus if he remembers the first computer he owned. [00:09:17] Ken asks Dr. Forbus if there was anything, other than its reputation, that led him to attend MIT. [00:10:09] James mentions that for the past few decades, Dr. Forbus has been working on developing “human like” AI systems. While much of AI research and development has been focused on meeting the standard of the Turing test, James asks Dr. Forbus why he is not a fan of the Turing test. [00:12:24] Ken mentions that Dr. Forbus received his Ph.D. from MIT in 1984, the same year that Apple released the first Macintosh, which was rolled out with a famous Super Bowl ad. This computer was the first successful mouse driven personal computer with a graphical interface. Ken asks Dr. Forbus what he remembers about that ad, and what his reaction to it was at the time. [00:13:22] James mentions that 1984 was also the year that Dr. Forbus made his first splash in the AI world with his paper on qualitative process theory. James goes on to explain that at the time, qualitative reasoning regarding quantities was a major problem for AI. In his paper, Dr. Forbus proposed qualitative process theory as a representational framework for common sense physical reasoning, arguing that understanding common sense physical reasoning first required understanding of processes and their effects and limits. James asks Dr. Forbus to give an overview of this paper and its significance. [00:18:10] Ken asks Dr. Forbus how it was that he ended up marrying one of his collaborators on the Structure Mapping Engine project, Dedre Gentner. [00:19:14] James explains that Dedre’s Structure Mapping Theory explains how people understand and reason about relationships between different situations, which is central to human cognition. James asks Dr. Forbus how Dedre’s theory was foundational for the Structure Mapping Engine (SME). [00:25:19] Ken mentions how SME has gone through a number of changes and improvements over the years, as documented in Dr. Forbus’ 2016 paper “Extending SME to handle large scale cognitive modeling.” Ken asks, as a cognitive model, what evidence Dr. Forbus has used to argue for the psychological and cognitive plausibility of SME. [00:30:00] Ken explains that many AI systems rely on deep learning, which is a subset of machine learning, using multi-layered artificial neural networks to automatically learn and extrapolate data. Ken goes on to say that Dr. Forbus has pointed out that both people and SME are able to learn successfully with far less data than deep learning requires. Ken asks Dr. Forbus to expand on this. [00:35:21] James mentions that Dr. Forbus has been working a lot over the past decade on companion cognitive architectures, which aim to reach human level AI, by creating software social organisms, which are systems that interact with people using natural modalities. Dr. Forbus elaborated on this in a 2016 paper titled “Software social organisms: Implications for measuring AI progress” where he argued that achieving human level AI is equivalent to learning how to create sufficiently smart software social organisms. James asks Dr. Forbus to briefly describe this concept. [00:44:18] James mentions that Dr. Forbus’ goal with this system is to create systems that can interact with people as apprentices or collaborators rather than just tools. In Dr. Forbus’ paper “Analogy and Qualitative Representations in the Companion Cognitive Architecture ,” he presents two hypotheses on how to create such systems. Starting with the first, James asks Dr. Forbus to elaborate on his hypothesis regarding analogical reasoning and learning, incorporating retrieval and generalization as well as SME capability for analogical matching. [00:48:38] Ken asks Dr. Forbus to elaborate on the second hypothesis, qualitative representations. [00:51:11] James asks if it is correct that Dr. Forbus’ key takeaway in this paper was that the models of structure mapping were particularly robust. [00:52:00] Ken pivots to discuss Dr. Forbus’ book “Qualitative Representations: How People Reason and Learn About the Continuous World” in which Dr. Forbus proposes that qualitative representations, which are symbolic representations that carve continuous phenomena into meaningful units, hold the key to one of the deepest mysteries of cognitive science and are central to human cognition. Ken asks Dr. Forbus to talk about his book and its key points. [00:57:32] James explains that Dr. Forbus followed up his book with a review in Science Direct, exploring how visual reasoning tasks involving comparison provide insights into how people make similarity and difference judgements. James goes on to mention that Dr. Forbus and his colleague Andrew Lovett summarized evidence that the same structure mapping comparison processes that seem to be used elsewhere in cognition can be used to model comparison in human visual reasoning tasks, and this relies on qualitative visual relationships computed using CogSketch, a model of high-level human vision. James asks Dr. Forbus to talk about these findings. [00:59:22] James mentions that Dr. Forbus and his colleagues published a paper about the importance of sketch worksheets in STEM classrooms. They argue that sketching can be a valuable tool for science, but it is currently underutilized. Dr. Forbus and his colleagues recommend sketch worksheets that use AI technology to give students immediate feedback and give instructors assistance in grading. James asks Dr. Forbus to explain what sketch worksheets are and how they can be helpful. [01:01:06] Ken asks Dr. Forbus to give some examples of homework that have been assigned with sketch worksheets. [01:02:34] Ken brings up another one of Dr. Forbus’ papers, which focused on the issues of adversarial attacks on ethical AI systems. The paper investigated moral axioms and the use of deontic logic in a norm learning framework. They found that adding axiomatic moral prohibitions and deontic inference rules to a norm learning model will make it less vulnerable to adversarial attacks. Ken asks Dr. Forbus to talk more about this. [01:07:09] James asks Dr. Forbus what his thoughts are on the idea that AI will soon begin to replace humans. [01:19:52] James explains that the impressive performance of deep learning systems, particularly LLM’s like ChatGPT has simultaneously made it harder for researchers to engage in building cognitively based systems. James asks Dr. Forbus for his thoughts on how we might lay the groundwork for continuing the important work in cognitively based systems. [01:22:54] Ken closes our interview by asking Dr. Forbus if he is thinking about retirement anytime soon. Links: Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio Ken Forbus bio

Today we have planetary scientist Dr. Pascal Lee and STEM-Talk host Dr. Ken Ford in a wide-ranging conversation about NASA’s ambitions to return humans to the Moon as a stepping stone to sending astronauts to Mars. Pascal is making his third appearance on STEM-Talk. Much of his research focuses on asteroids, impact craters, and the future human exploration of Mars. Pascal and Ken have a lively discussion about the growing momentum for space exploration. Pascal is a researcher at the SETI Institute, a not-for-profit NASA program focused on searching for extraterrestrial intelligence in an effort to understand and explain the origin and nature of life in the universe. He also is the co-founder and chairman of the Mars Institute, and director of the Haughton-Mars Project at NASA Ames Research Center. Last year, Pascal received significant news coverage for his discovery of a giant volcano along with a possible sheet of buried glacier ice in the eastern part of Mars' Tharsis volcanic province. This was the first geological find of this magnitude since the other major volcanos on Mars were discovered back in the 1970s. Show notes: [00:03:06] Ken welcomes Pascal back to STEM-Talk and starts our interview by mentioning the developments in space exploration over the past few years, including civilian space missions, NASA’s Artemis program which aims to send humans back to the moon, and commitments to a manned mission to Mars. Given Pascal’s career in advancement of space exploration, Ken asks if Pascal is excited by these recent developments. [00:04:43] Ken explains that for a couple of decades Pascal has spent his summers visiting Devon Island in the Canadian arctic archipelago, which is the largest uninhabited land on Earth. When Pascal was last on STEM-Talk, his annual trip to Devon Island was cancelled due to COVID-19. Devon Island has unique geological characteristics that are in some ways similar to those on Mars. Since 2001, Devon Isalnd has been the home of the Haughton Mars Project (HMP). Ken asks Pascal to talk about the advances in this project since his last appearance on STEM-Talk. [00:07:59] Ken mentions that while much conversation has been centered on a human trip to Mars, a mission to return humans to the Moon and establish a permanent base is a more immediately feasible goal in the short term. Ken asks Pascal to talk about the importance and significance of such a mission. [00:12:06] On the topic of a Moon base, Ken explains that NASA’s Artemis project aims to send humans to the south pole of the Moon. Pascal has written a paper on that topic titled “An Off-Polar Site Option for the NASA Artemis Space Camp.” Ken asks Pascal what he sees as the primary weakness in the south pole location. [00:20:25] Ken agrees with Pascal’s perspective on sending humans to the lunar south pole, and the two discuss the problems with focusing human space exploration on romantic ideas such as “living off the land.” [00:22:24] Ken follows up on the previous questions by mentioning that in Pascal’s aforementioned paper, he suggests setting up a lunar base at the floor of the Clavius crater. Ken asks Pascal to talk about Clavius and why it is a potentially good permanent location for a moon base. [00:27:56] Ken asks Pascal how confident he and the community at large is in the Sophia finding of water. [00:29:00] Ken notes that contemporary interest in human space exploration appears tied to current geopolitical issues, much like the first space race between the US and USSR. Today, interest in space travel is closely linked with relations between the US and China. Ken asks Pascal to discuss this and how he believes the US should view this current situation. [00:35:43] Ken asks Pascal what he knows about the China’s current plans for a lunar mission. [00:34:36] Ken talks about a meeting at IHMC that addressed power-beaming to the lunar surface. [00:39:01] Ken notes that there is a lot of talk these days about not not only traveling to Mars, but also colonizing Mars. Ken asks Pascal where he believes this sentiment is coming from and what are some of the challenges associated with colonizing Mars. [00:46:48] Ken notes that last year Elon Musk made an announcement to his SpaceX employees that he expects 1 million people to be living on Mars in the next 20 years. Ken asks Pascal what his thoughts are on this. [00:53:28] Ken asks Pascal to talk about a paper he published discussing a previously unrecognized volcano on Mars. Given that it was generally accepted for decades that all the volcanos had been accounted for, Ken asks Pascal to talk about the story of his recent discovery. [01:02:44] Ken pivots to a discussion of the Moons of Mars, specifically Phobos, asking Pascal to talk about the nature of this Moon. [01:07:42] Ken mentions that docking on Phobos and then going from Phobos to Mars would likely be a safer strategy for early Mars missions than landing directly on Mars from Earth. [01:12:30] Ken starts a discussion about Perseverance, as well as the new Japanese mission that may bring back Mars rocks from Phobos. Ken asks Pascal about Perseverance’s collection Mars’ of rock samples that NASA plans for a mission to bring those Mars rocks to Earth. Ken asks it is worth the cost of a mission to collect these samples and what we might learn if we are successful in getting these samples to Earth. [01:17:09] Ken wraps up our interview asking Pascal what year it was that he started working at NASA Ames, which turns out to be the same year Ken started working at NASA Ames. Links: Pascal Lee bio Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page

Today we have JP Errico, a scientist and inventor whose work focuses on neuroimmunology and the many ways it impacts cellular metabolism, inflammation, mental health and how we age. He recently joined IHMC as a Senior Research Scientist. JP is particularly known for his research on vagus-nerve stimulation and is the author of the book, The Vagus-Immune Connection: Harness Your Vagus Nerve to Manage Stress, Prevent Immune Dysregulation, and Avoid Chronic Disease. He also is the co-host of the podcast, The Health Upgrade. JP has more than 250 patents and is the founder of ElectroCore, a company that specializes in neuromodulation and noninvasive vagus-nerve stimulation. He has an undergraduate degree in aeronautical engineering from the Massachusetts Institute of Technology and worked at Lincoln Laboratories. JP also holds graduate degrees in both law and mechanical/materials engineering from Duke University. Show notes: [00:03:08] Tim opens our interview mentioning that as a child JP was focused on both sports and academics. [00:04:50] Tim talks about how hard it is to find quality math and science education today similar to what JP experienced at his high school. [00:05:16] Tim asks JP what it was that led him to pursue an undergraduate degree at MIT. [00:05:53] Tim asks if it was always JP’s plan to go into aeronautical engineering. [00:07:22] Tim mentions that as a kid, JP would scour bookstores and libraries for textbooks on physics and quantum mechanics and asks JP if there were any books that particularly inspired him. [00:10:12] Ken mentions that after MIT, JP went to Duke University where he pursued mechanical engineering and also went to law school. Given this workload, Ken asks if JP ever had any free time while studying at Duke. [00:13:26] Tim mentions that while JP was in law school, he got a job at a patent firm. After obtaining his law degree, JP’s uncle called and offered JP an opportunity. [00:17:42] Tim explains that JP’s career has focused on neuroimmunology, or the study of how the nervous system and immune system interact. Neuroimmunology affects a wide range of health factors including inflammation, mental health and aging. Tim also explains that JP has recently authored a book on neuroimmunology titled “The Vagus Immune Connection: Harness Your Vagus Nerve to Manage Stress, Prevent Immune Dysregulation and Avoid Chronic Disease.” Tim asks JP to touch on the key features of neuroimmunology that people should be aware of. [00:21:59] Tim asks JP to touch on the epigenetic factors regarding neuroimmunology. [00:25:01] Since JP brought up Dr. Kevin Tracey’s work, Ken mentions that Kevin was recently interviewed on STEM-Talk episode 172 and encourages listeners to listen to that episode for more context on the vagus nerve and neuroimmunology. [00:25:48] JP talks about how he stumbled upon the idea of how stimulating a nerve may have the same clinical benefit that sometimes occurs as a result of cutting a nerve. [00:28:16] Tim talks about the unintended consequences he observed as surgeon when he cut a patient’s vagus nerve. [00:30:50] Ken mentions that another area where JP has had impact with respect to stimulating the vagus nerve is the treatment of asthma and asks JP to talk about his findings in this area. [00:40:10] Tim notes that after JP knew that non-invasive approaches to vagus-nerve stimulation were possible, he went on to optimize a delivery device. These efforts resulted in a device called gamaCore. Tim asks JP to talk about this device and how it works. [00:43:27] Tim asks JP to talk about what it feels like for patients to have their vagus nerve stimulated. [00:44:50] Ken asks if JP thinks that his and others’ work in vagus-nerve stimulation inspired the development of similar devices for orthopedic pain, where the device is implanted near the nerve on the knee or other area experiencing pain. [00:50:41] Tim starts a conversation about a program at DARPA called Targeted Neuroplasticity Training, or TNT, which investigated ways to stimulate the nervous system to treat various conditions like pain and phantom pain. Before jumping into that topic, however, JP discusses depression and how inflammation and the vagus nerve play a part in serotonin and melatonin production. [00:55:39] Ken asks JP why stimulating the vagus nerve has such a breadth of applications and benefits. [01:01:57] Given the success of vagus-nerve stimulation in affecting a wide variety of health outcomes as well as improving learning, there are many individuals interested in trying vagus-nerve stimulation for themselves. Tim asks JP what advice he has for people looking to try vagus-nerve stimulation. [01:09:39] Tim notes that in his use of various vagus-nerve stimulation devices in studies he has conducted, there are varying outcomes. Given this, Tim asks JP what devices he recommends. [01:11:50] Ken asks JP to talk about the development of the Truvaga device. [01:13:47] Ken closes our interview mentioning again JP’s book, “The Vagus Immune Connection: Harness Your Vagus Nerve to Manage Stress, Prevent Immune Dysregulation and Avoid Chronic Disease,” and encourages listeners to check it out. Links: Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Tim Broderick bio JP Errico bio

Today we have Dr. Karl Herrup, a neurobiologist known for his investigations into the roles that DNA damage and noncoding genetic variants have in Alzheimer’s disease. Joining Ken today to interview Karl is Dr. Tommy Wood, a visiting scientist here at IHMC.  Tommy also is an associate professor of pediatrics and neuroscience at the University of Washington, where he focuses on brain health across lifespan. He has been our guest several times on STEM-Talk and we will have links to those interviews in our show notes for today’s episode. After more than a century of research, the underlying cause of Alzheimer’s remains a mystery. For the past few decades, the leading theory has been the amyloid cascade hypothesis, which proposes that abnormal amyloid plaques in the brain are the central cause of the disease. Today we talk to Karl about his lab and research as well as his view that the amyloid cascade hypothesis is not only flawed,  but also could be holding back research for a cure of Alzheimer’s. A professor of neurobiology and an investigator in the Alzheimer’s Disease Research Center at the University of Pittsburgh School of Medicine, Herrup is the author of How Not to Study a Disease: The Story of Alzheimer’s. Show notes: [00:03:50] Tommy asks Karl what he was like as a kid to open the interview. [00:04:36] Tommy asks Karl about his educational environment growing up. [00:05:10] Ken mentions that Karl went to Brandies University originally with the intent of becoming a physician and asks Karl what happened to change his mind. [00:06:14] Ken asks Karl if it is true that his father was disappointed with Karl’s decision to abandon medical school in favor of genetics. [00:07:02] Tommy mentions that Karl began researching genetics in the late 1960s when researchers were just beginning to unravel the secrets of DNA. Tommy asks Karl to discuss why this was such an exciting time to study genetics. [00:08:38] Tommy asks Karl what prompted him to pursue a PhD in neuroscience. [00:11:34] Continuing on the theme of happy accidents, Ken asks if it was also an accident that led to Karl moving to Switzerland for a second post-doc. [00:12:36] Ken asks Karl to expound on his experience taking an overseas post-doc, which was not a common practice in the 1970s. [00:14:11] Ken mentions that Karl has seemed to benefit in his life from the combination of preparation and the willingness to explore opportunities that present themselves. [00:15:00] Tommy mentions that when Karl arrived back in the US from Switzerland, he accepted a faculty position at Yale and asks him to discuss this experience. [00:17:06] Tommy mentions that after Yale, Karl had several faculty appointments, including a seven-year stint in Hong Kong, and asks Karl to talk about that experience. [00:21:36] Tommy asks Karl why, in 2019, he moved back to his hometown to become a professor of neurobiology at the University of Pittsburgh and co-investigator at the university’s Alzheimer’s research center. [00:24:45] Ken asks Karl to talk about his lab at the University of Pittsburgh, which focuses on the biology of neurodegeneration. [00:26:32] Ken asks Karl if there was anything specific that caused him to shift his focus at this stage in his career so heavily towards Alzheimer’s research. [00:28:21] Tommy comments on Karl’s hypothesis of the aging brain, noting that it would make sense for the same processes involved in the developing brain to relate to what we see in the aging brain, as these processes are continuous throughout the lifespan. [00:29:54] Tommy pivots to talk about Karl’s book, entitled “How Not to Study a Disease: The Story of Alzheimer’s” for which Karl interviewed a number of experts and colleagues, asking each one to define Alzheimer’s disease in their own words. [00:30:51] Tommy reiterates the point that we still do not have a universally accepted definition of Alzheimer’s disease and asks Karl why this is such a critical problem for the field. [00:32:27] Ken asks if Karl has a working definition of Alzheimer’s disease. [00:33:47] Ken explains that Karl begins his book with the story of a woman named Dorothy, who after living a vibrant life and taking good care of herself as she aged, fell victim to Alzheimer’s disease. Ken asks Karl to talk about Dorothy, and why he chose to begin his book with her story. [00:36:58] Tommy asks Karl to define the difference between Alzheimer’s and dementia more broadly. [00:38:00] Tommy explains that while Alzheimer’s is typically characterized as a disease of late life, early onset Alzheimer’s, while rare, is possible, typically very aggressive, and generally runs in families. Tommy asks Karl to explain how we differentiate late and early onset Alzheimer’s. [00:38:58] Ken asks Karl to explain how one differentiates Alzheimer’s from other forms of dementia in a clinical context. [00:41:53] Ken points out that the title of Karl’s book “How Not to Study a Disease” highlights that assumptions about Alzheimer’s disease potentially have misdirected research in some ways. Ken asks Karl to talk about this misdirection and its consequences. [00:43:37] Tommy gives some background on the amyloid cascade hypothesis, explaining that Dr. Alzheimer himself was not entirely convinced that the cases he had been studying were necessarily representative of a single condition.  Dr. Alzheimer’s mentor, Dr. Kraepelin, coined the disease in a book that he was writing. Tommy also mentions that Karl has said that this is one of three key events that cemented the amyloid cascade hypothesis as the leading hypothesis of Alzheimer’s disease and asks Karl to discuss more of this history. [00:49:20] Tommy asks Karl to give an overview of the amyloid cascade hypothesis. [00:53:36] Ken explains that Karl sees the amyloid cascade hypothesis as failing three basic tests. Ken goes on to ask Karl to discuss, in depth, the first test, which is the fact that in both humans and mice the addition of amyloid to healthy brains does not trigger an amyloid cascade. [00:56:55] Tommy moves to Karl’s second test of the amyloid cascade hypothesis, the fact that removal of amyloid from the brains of mice and humans does not stop Alzheimer’s disease processes. Given the recent FDA approval of several anti-amyloid drugs, Tommy asks Karl to give his thoughts on the history of anti-amyloid therapies. [01:03:29] Ken explains that the third test of the amyloid cascade hypothesis entails blocking the formation of amyloid from the amyloid precursor protein, which was not only found to not stop Alzheimer’s progression, but in fact makes humans and mice sicker. [01:05:47] Ken takes a moment to clarify that Karl is not arguing that amyloid has no role in Alzheimer’s disease, just that it is not the primary cause of Alzheimer’s. [01:06:21] Ken asks Karl what his response is when people ask what he proposes the cause of Alzheimer’s is if it’s not amyloid. [01:08:45] Tommy asks Karl to elaborate on the idea of the emergent nature of the brain and the potential for this emergence to help explain Alzheimer’s disease. [01:10:54] Ken mentions that the last section of Karl’s book is titled “Where Do We Go From Here” in which he argues that because age is an absolute prerequisite for Alzheimer’s, there is no solution to the problem of dementia that does not rely heavily on an understanding of the process of aging. Ken goes on to explain that much of this was originally posited in Karl’s 2010 paper Reimagining Alzheimer’s disease: An age-based hypothesis. Ken goes on to ask Karl to talk about his view that developing an age-based hypothesis is going to be difficult given that aging is one of the greatest unsolved mysteries in biology. [01:13:19] Ken mentions that aging research gets a very small amount of funding in comparison to the myriad disorders for which aging is the primary risk factor. [01:16:11] Tommy shifts gears to talk about a series of studies that Karl conducted on the benefits of exposure to Japanese gardens on the clinical symptoms of Alzheimer’s disease. In one of these studies, Karl found that the Japanese garden not only relieved physiological stress but also improved qualitative measures such as verbalization and memory retrieval. Tommy asks Karl how he became interested in Japanese gardens, and if the results of his experiments surprised him. [01:20:33] Tommy comments that Karl’s work on the effects of Japanese gardens on the clinical symptoms of Alzheimer’s contributes to a larger body of literature showing the critical importance of the environment in shaping and maintaining cognitive function. Tommy goes on to say that the decline in certain cases of Alzheimer’s can be matched to the increasing levels of institutionalization and the decrease of enriching stimuli in a patient’s environment as their disease progresses. Tommy asks Karl to talk about the importance of social, cognitive, and environmental stimuli for cognitive function. [01:23:34] Ken mentions that Karl has pointed out in the past that non-pharmacological approaches to treating Alzheimer’s have been the most effective tools in our arsenal so far. Given this, Ken asks Karl what he recommends to people for their brain health and cognitive function. [01:25:22] Ken explains that Karl is involved with, or supports, at least two charitable organizations that aim to reshape the face of funding for Alzheimer’s research, namely the Coins for Alzheimer’s Research Trust, and the Clear Thoughts Foundation. Ken asks Karl to talk about his relationship to these organizations and what he hopes will change in the landscape of Alzheimer’s research funding. [01:27:23] Tommy closes our interview asking whether Karl has a Japanese garden of his own in his back yard. Links: About IHMC Karl Herrup bio Ken Ford bio Ken Ford Wikipedia page Tommy Wood bio

Today we have Dr. Frank Butler, a retired Navy Undersea Medical Officer and an ophthalmologist who served as a Navy SEAL platoon commander prior to attending medical school. Just a few weeks after our interview, President Joe Biden awarded Frank a Presidential Citizens Medal during a White House ceremony. The medal is one of the highest honors a civilian can receive and recognized Frank’s many contributions to civilian and military trauma care. Frank is credited with founding Tactical Combat Causality Care, also known as TC Three, which has transformed battlefield medical care and saved thousands of lives.  TCCC is now used throughout the U.S. military and much of the world. In today’s interview, we talk to Frank about his recent book, “Tell Them Yourself: It’s Not Your Day to Die,” which describes the challenges and improvements TCCC has experienced over the past three decades. Frank spent most of his 26-year career in Navy Medicine supporting the Special Operations community. He served a five-year stint as a Diving Medical Research officer at the Navy Experimental Diving Unit in Panama City, Fla., where he helped develop many of the diving techniques and procedures used by Navy SEALs today. Show notes: [00:03:31] Dawn opens the interview asking Frank what it was like growing up in Savannah, Ga., in the 50s and 60s. [00:04:40] Dawn asks Frank about his father, who was an industrial engineer, and who became director of urban housing in Savannah during a time when the city was developing public housing. [00:05:47] Ken asks Frank if it’s true that most of his family went into the medical field. [00:06:33] Ken asks Frank about his experience attending a Navy SEALs demonstration during his sophomore year of college. [00:08:09] Dawn asks Frank about his experience going through Navy SEAL training, particularly the Basic Underwater Demolition SEALs School. [00:09:29] Dawn asks if it’s true that five people in Frank’s family have become Navy SEALs. [00:10:08] Ken explains that after Frank left the SEALs in 1975, he had to figure out what to do next with his life. Frank talks about what led to his decision to go to medical school. [00:11:14] Ken asks Frank how he ended up at Jacksonville Naval Hospital to do an internship in family medicine. [00:11:46] Dawn explains that after Frank’s internship, he was assigned to the Navy Experimental Dive Unit. She asks him to talk about this experience. [00:12:25] Frank talks about some of the projects he worked on during this period. [00:14:43] Ken asks Frank how he decided on ophthalmology as his surgical specialization. [00:15:47] Dawn asks Frank what his experience as a resident at Bethesda Naval Hospital was like. [00:16:52] Dawn explains that after Frank completed his residency, he was assigned to Pensacola Naval Hospital. Dawn asks Frank how he ended up becoming the biomedical research director for the Navy SEALs. [00:18:48] Ken mentions that Frank worked on several important projects as research director for the SEALs, including battlefield trauma care, a tactical athlete program, improved treatment of decompression sickness, and the Navy SEAL nutrition guide. Ken begins by asking Frank to talk about his work on the tactical athlete program. [00:20:33] Dawn explains that another one of Frank’s projects as research director for the SEALs was the design of the Navy special warfare decompression computer. Dawn asks Frank to explain what a decompression computer does for a diver. [00:21:35] Dawn asks Frank to elaborate on the process of designing this decompression computer and the algorithm as well as the process of getting it approved for the Navy. [00:23:31] Ken asks Frank to talk about a program he worked on to promote refractive surgery. While this program was initially designed to improve combat vision for SEALs, the program has expanded to all active-duty service members, including aviators. [00:26:26] Dawn explains that Tactical Combat Casualty Care (TCCC) has been an incredible transformation in battlefield trauma care, with literature indicating that the protocols have saved thousands of lives. TCCC is now used throughout the US military and much of the rest of the world. Dawn goes on to ask about Frank’s book “Tell Them Yourself: It’s Not Your Day to Die,” which documents how TCCC has evolved over the three decades since it was first introduced, as well as the trials and tribulations the program endured. [00:28:04] Ken asks Frank to elaborate on the assertion in his book that, save for the use of helicopters in place of horse drawn carriages, pre-hospital battle trauma care was essentially the same as it was during the Civil War prior to TCCC. [00:30:05] Following up on the discussion of tourniquets, Ken mentions his memory of the outright ban of tourniquets in the Navy during his time in the service. [00:31:07] Ken asks Frank how he was able to take his realization that something needed to be done about battlefield trauma care and turn that into a Navy project. [00:32:58] Dawn asks Frank how, as program manager, he approached the conduct of the TCCC research project. [00:35:03] Dawn asks Frank why, even though the TCCC paper came out in 1996, TCCC was still not widely used in the U.S. military at the beginning of the war in Afghanistan. [00:36:14] Frank recalls the first unit to implement TCCC. [00:37:10] Dawn asks what other units followed as early adopters. [00:39:26] Dawn asks Frank how he helped implement TCCC throughout the special operations community. [00:43:11] Ken mentions that some units did particularly well in adopting TCCC and others struggled. Given this, Ken asks if the operational leader’s priority regarding TCCC impacts the implementation of it in the unit. [00:44:31] Ken asks Frank to speak on the adoption and implementation of TCCC in the rest of the military outside of the special operations communities. [00:47:32] Dawn asks Frank how he updated his recommendations for TCCC as new evidence from the war came in. [00:50:31] Ken asks Frank, other than tourniquets, what medical advancements to battlefield trauma care did TCCC usher in. [00:54:31] Ken mentions that while the TCCC innovation of carrying whole blood and performing pre-hospital blood transfusions has saved countless lives, the innovation still is not ubiquitous in the military or for civilian first responders. Ken asks Frank to talk about the complexities of a ubiquitous adoption of this practice, and what can be done to push it forward. [01:00:06] Dawn asks, in addition to tourniquets and whole blood, what are some of the TCCC innovations that are now being widely used in the civilian world. [01:03:19] Ken pivots to a discussion about ketamine. Ken notes that the U.S. military, as well as the militaries in other countries, have used ketamine as an anesthetic, especially since the war in Afghanistan.  Ken notes that the civilian world has been slow to adopt ketamine as a drug for pain relief. Frank gives his thoughts broadly on the use of ketamine as an anesthetic and his belief that it will become more common in civilian EMS units over the next five to 10 years. [01:07:34] For listeners who are interested in learning more about the medical uses of ketamine, Ken recommends Episode 165 with Dr. Jonathan Edwards. [01:09:03] Ken and Frank have a tangential discussion about ketamine as a treatment for suicidal ideation and depression. [01:11:11] Ken asks Frank, given that the TCCC protocols have been widely adopted in every area of the military, what is the basic level of competence in TCCC that every service member should have. [01:14:26] Ken asks Frank to speak to the situation in Ukraine with respect to combat casualty care. [01:17:23] Looping back to Frank’s book “Tell Them Yourself: It’s Not Your Day to Die,” Dawn asks why Frank took up the task of writing it. [01:21:20] Dawn asks Frank about the significance of the book’s title. [01:22:04] Dawn mentions that many people speak about how compelling the first chapter of Frank’s book is. Dawn asks Frank to talk about the writing process for this chapter. [01:25:05] Dawn mentions that one of Frank’s co-authors for his book is Dr. Kevin O’Connor, who is currently the physician to the president. Given that Frank was in the Navy and Dr. O’Connor was in the Army, Dawn asks Frank how the two of them met. [01:26:42] As we near the end of our interview, Ken asks Frank if he has any final insights to share about battlefield trauma care. [01:28:11] Ken comments on the importance of Frank’s book as a marker, so we don’t forget hard won lessons during times of peace. [01:29:47] Dawn closes our interview with Frank by mentioning that he is an avid diver and asks him what his favorite spot to dive is. Links: Frank Butler Presidential Citizens Medal Frank Butler IHMC lecture and bio Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio

Dr. Alessio Fasano, who is considered the world’s leading expert in celiac disease and gluten-related disorders, returns for his second appearance on STEM-Talk. Although just 2 million Americans have celiac disease, an estimated 20 million Americans suffer from gluten sensitivity. Alessio is a professor and director of the Mucosal Immunology and Biology Research Center at Massachusetts General Hospital. In addition to celiac disease and gluten-related disorders, Alessio’s research is also focused on the microbiome, intestinal permeability and autoimmune disorders, which he discussed in his first interview on STEM-Talk, episode 20. Since Alessio’s first appearance on STEM-Talk in 2016, he has published two books, “Gluten Freedom” and “Gut Feelings: The Microbiome and Our Health,” which we discuss in today’s interview. We also talk to Alessio about an exciting new project that’s bringing together an international consortium of researchers and scientists for a long-term study that will follow infants who are genetically at risk of developing celiac. Alessio is a researcher and physician who wears many hats. He is the director of the Center for Celiac Research and Treatment and chief of the Division of Pediatric Gastroenterology and Nutrition at Mass General Hospital. He also is a professor of pediatrics at Harvard Medical School and a professor of nutrition at Harvard’s T.H. Chan School of Public Health. Show notes: [00:03:58] Marcas opens the interview welcoming Alessio back to STEM-Talk, mentioning that since his last appearance he has written two books: Gluten Freedom and Gut Feelings: The Microbiome and Our Health. Marcas asks Alessio how he became interested in pediatrics and gastroenterology. [00:05:42] Ken mentions that Alessio moved to the U.S. in the 1990s and spent 20 years in Maryland at the Center for Vaccine Development in Baltimore. Ken goes on to mention that while Alessio was there, he founded The Center for Celiac Research in 1996, and in 2003, Alessio accepted an offer to join Massachusetts General Hospital. Ken asks how that move came about. [00:08:53] Marcas asks about Alessio’s early career working on cholera, where he discovered the zonula occuldens toxin, the bacteria that causes cholera. Marcas asks Alessio to talk about this finding and the insights he gleaned from it. [00:16:03] Ken asks about Alessio’s discovery of zonulin, which is the molecule that modulates gut permeability in humans. Ken asks Alessio to share how this discovery led him to investigate celiac disease, which is triggered by gluten. [00:20:25] Ken asks Alessio what his thoughts are on why the medical community, historically, has not taken celiac disease seriously. [00:24:08] Marcas mentions that as we age, there is evidence that the gut becomes leakier, which is highly related to chronic inflammation. Marcas asks Alessio whether this happens to the gut over time due to diet and lifestyle rather than the typical aging process. [00:28:45] Ken mentions that there has been an increase in the diagnosis of celiac disease. Ken asks Alessio if that is due to an actual increase in the prevalence of the disease, or is it tied to a growing appreciation that clinicians have now for the disease? [00:29:32] Marcas mentions that Alessio’s book, Gluten Freedom, which he co-authored with his colleague Susie Flaherty, was referred to by the Celiac Disease Foundation as “a must have,” and “an excellent reference for those with gluten related disorders.” Marcas asks Alessio about this reception to his book. [00:31:24] Marcas mentions that the only viable treatment for individuals with celiac disease has been a gluten-free diet, with pharmaceutical companies having had little interest until recently in investigating the disease. Now there are more than 20 drug therapies in development for celiac. Marcas asks Alessio about the progress being made to develop pharmacological interventions for celiac. [00:34:17] Ken mentions that gluten sensitivity affects more than 20 million Americans. This sensitivity is when a person reacts negatively to the gluten protein but does not test positive for celiac. Ken mentions that this condition is often underappreciated by physicians and asks Alessio to discuss gluten sensitivity and its impact. [00:40:41] Marcas points out that celiac disease is a disorder with genetic components. A group of genes called HLADQ and DQI genes are involved in the development of the disease. About a third of the population inherits these genes, but not everyone who possesses them will develop celiac. Marcas asks Alessio to elaborate on this phenomenon. [00:42:51] Marcas asks Alessio to talk briefly about his book Gluten Freedom. [00:43:40] Ken asks about the experience Alessio had working with Bob Prior at MIT Press, the publisher of Gluten Freedom. [00:47:07] Ken mentions that Alessio has expressed in the past that he does not like the term “leaky gut,” which can be offered as a diagnosis, and asks Alessio why that is. [00:49:38] Ken mentions Alessio gave a talk in 2018 at the Institute for Functional Medicine’s annual conference titled: “Autoimmunity and the Interplay of Genes and the Environment.” Ken explains that this talk began by pointing out that medicine is still largely ignorant of certain aspects of human biology, and how and why people get sick. Ken asks Alessio to discuss the main points of this talk. [00:52:21] Ken mentions that in researching “Gluten Freedon” that Alessio consulted with Claire Fraser who was our guest on episode 32. Ken asks Alessio how he met Claire. [00:55:28] Marcas pivots to talk about Alessio’s current work, namely his recent project “The Celiac Disease Genomic Environmental Microbiome and Metabolomics Study.” Marcas goes on to explain that this project will follow infants from birth through childhood in an effort to better understand the many factors that contribute to the development of celiac. [01:06:12] Ken mentions that for this study, Alessio recruited not only American families but also participants from Spain and Italy, asking what the rationale was for those populations. [01:07:14] Marcas asks if the overarching goal of this study is to pave the way for personalized prevention of celiac disease. [01:08:37] Marcas asks about a paper Alessio published in the American Journal of Gastroenterology titled: “Early Antibody Dynamics in a Prospective Cohort of Children At-Risk for Celiac Disease,” which aimed to identify possible serum biomarkers that could help predict celiac disease in at-risk children. Marcas asks Alessio to talk about the design of this study and its findings. [01:10:14] Ken pivots to talk about a study Alessio published earlier this year in the Journal Pediatrics on zonulin. Ken explains that this study evolved from the observation that increased intestinal permeability appears to be a key factor in several autoimmune diseases including celiac. However, the question remains whether increased permeability of the intestines precedes disease onset or if it is a consequence of disease onset. Ken asks Alessio to touch on this study and its findings. [01:11:41] Marcas mentions that as a pediatric gastroenterologist, Alessio also works with children on the autism spectrum, who in addition to social challenges and repetitive behaviors deal with a variety of symptoms. Marcas asks Alessio to talk about his experience working with these children. [01:16:27] Ken mentions that when we last had Alessio on STEM-Talk, he was in the middle of renovating a 13th century monastery into the European Biomedical Research Institute of Salerno. Ken asks Alessio to give an update on this project. [01:19:54] Marcas mentions that Alessio’s son, Stefan, has joined IHMC as a research associate. Marcas asks Alessio how Stefan is liking it here at IHMC. [01:22:56] Marcas ends the interview asking Alessio if he will write another book. Links: Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Marcas Bamman Alessio Fasano

Today we have Dr. Nicholas Norwitz, 28, a third-year Harvard Medical School student whose research into the applications of a ketogenic diet as metabolic medicine has attracted a significant following. For a number of years during his youth, Nick suffered from a number of debilitating diseases, including osteoporosis, ulcerative colitis, and inflammatory bowel disease.  In today’s interview, we talk to Nick about research that led him to adopt a ketogenic diet that put him back on the road to metabolic health. After graduating from Dartmouth College in 2018 with a degree in cellular and molecular biology, Nick attended Oxford University where he earned a Ph.D. in metabolism and nutrition. He is the author of peer-reviewed scientific papers and textbook chapters on topics including Alzheimer’s disease, cardiovascular disease, diabetes, gastrointestinal health, genetics osteology and Parkinson’s disease. Show notes:  [00:02:53] Marcas opens the interview mentioning that Neck grew up in Boston, and asks if it’s true that he was a very curious kid growing up. [00:04:09] Marcas asks Nick if as a young child he always knew he wanted to be a physician and a scientist. [00:05:40] Ken mentions that Nick was a runner in high school, and as is the case with many runners, this led to fractures. However, Ken goes on to say that these fractures did not resolve for Nick, and asks what he learned as a result. [00:11:08] Ken asks about Nick’s eating habits in college as he loved to cook and bake. [00:15:40] Marcas follows up, asking Nick at what point during his Ph.D. training was he admitted to palliative care. [00:21:01] Marcas pivots to talk about the need for incorporating metabolic health into our health-care system. He mentions that Nick once said that “we live in a society where our social norms and ecosystem, with respect to health and food, are extremely dysfunctional,” and asks Nick to elaborate on this. [00:26:16] Ken mentions a paper that Nick recently published titled, “Oreo Cookie Treatment Lowers LDL Cholesterol More Than High Intensity Statin Therapy in a Lean Mass Hyper-Responder on the Ketogenic Diet: A Curious Crossover Study.” To provide some background, Ken mentions that some people on a ketogenic or low carb diet experience a dramatic increase in LDL cholesterol. The rationale behind Nick’s paper being that if it is the removal of carbohydrates that causes this increase in LDL, adding carbohydrates back into one’s diet should bring LDL levels back down. Ken asks Nick to talk about this experiment and how he designed it. [00:35:44] Ken mentions that the paper seems to be designed to be provocative, as simply testing carbohydrates against statins would likely have not gotten as much attention as using Oreo cookies. [00:37:00] Marcas mentions that in the Oreo cookie vs statin experiment, Nick’s original fasted-morning LDL was 384, before dropping it with Oreos, then doing a washout before dropping it again with statins. Marcas asks Nick what his fasted-morning LDL was post washout, prior to the statin intervention. [00:39:07] Marcas brings up Nick’s paper titled: “The Lipid Energy Model: Reimagining Lipoprotein Function in the Context of Carbohydrate Restricted Diets.” Marcas goes on to mention that the aim of the paper was to propose a mechanistic explanation for the “lean mass hyper-responder phenotype.” Marcas asks Nick to give listeners an overview of the lipid-energy model. [00:45:18] Ken mentions that according to Nick, BMI is not a requirement for classification as a lean mass hyper-responder. Nick’s paper, however, uses BMI data. Ken mentions that he finds BMI relatively useless and asks why Nick did not use DEXA scans instead. [00:48:52] Ken mentions that adipose tissue contains roughly 25 percent of total body cholesterol, and we know that LDL binding to adipose cell membranes is competitively inhibited by HDL. Ken asks if lean mass hyper-responders were found to have low fat mass as a defining feature, how might this effect the lipid panel in terms of LDL-C. [00:50:50] Ken explains that the thinking regarding HDL is currently being refined, with current ideas regarding HDL all-cause mortality currently conforming to a U-shaped curve. Ken asks, with respect to lean mass hyper-responders, what sort of health risks these high HDL levels might confer. [00:53:50] Marcas asks Nick how the lipid-energy model would apply in the population of lean people with respect to the difference between untrained individuals and highly trained athletic people, and if he can envision a study to tackle that question. Marcas goes on to ask when Nick thinks would be the best time to acquire samples in this hypothetical study, relative to bouts of exercise. [00:57:55] Marcas mentions that the European Society of Cardiology and the European Society of Atherosclerosis came out with a consensus in 2019 on the superiority of apolipoprotein B measurement of serum cholesterol levels as an indicator of risk. Marcas goes on to mention that while apolipoprotein B was not measured in Nick’s Oreo study, his high LDL measurement was correlated with a high LDL particle count, meaning that lean-mass hyper responders might have a high apolipoprotein B and or high-particle count, which could translate to risk for cardiovascular disease. Marcas asks Nick what his thoughts are on how people on low carb diets should navigate high apolipoprotein B levels. [01:01:09] Marcas pivots to ask about a piece that Nick wrote on a website called Stat, which is a journalistic site covering health, medicine, and life science. The piece detailed Nick’s concern going into medical school that being on the ketogenic diet would make him something of a pariah. Marcas asks how his experience in med school is now three years later, and whether or not he is in fact a pariah. Links: Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Marcas Bamman bio Nick Norwitz bio

Dr. Vyvyane Loh returns to STEM-Talk for her second appearance to talk about atherosclerotic heart disease. Also known as ASCVD, the disease has been reported to affect 26 million people in the U.S., and annually leads two million hospitalizations and more than 400,000 deaths. Vyvyane is a board-certified physician in obesity and internal medicine. In episode 142 of STEM-Talk, we talked to Vyvyane about her Boston-based preventative-care practice that specializes in weight management and the treatment of chronic metabolic diseases such as diabetes, hypertension and dyslipidemia. In today’s podcast, Vyvyane and host Dr. Ken Ford talk about ASCVD as well as recent research that has shown substantial individual variability in the response to statin therapy as a way to lower cardiovascular risk. Vyvyane and Ken also discuss how the current knowledge base informing clinical practice in medicine today is far behind advances in the biological sciences, especially in the field of ASCVD. Show notes:  [00:03:15] Ken welcomes Vyvyane back to STEM-Talk and encourages listeners to check out Vyvyane’s first interview, episode 142. Ken goes on to mention that atherosclerotic heart disease has been reported to affect 26 million people in the U.S. and that despite the wide use of statins as a primary prevention of atherosclerotic heart disease, the effects of this treatment have been variable with regards to major adverse cardiac events. Ken asks Vyvyane for her thoughts. [00:05:32] Ken asks Vyvyane about recent developments in atherosclerotic heart disease research, specifically in regard to the anatomical aspects of the disease-model itself. [00:08:43] Ken follows up asking Vyvyane how the knowledge we have of glycocalyces, and the endothelial lining of the blood vessels, could affect clinical practice. [00:12:19] Ken asks if there are any other recent updates to the anatomical model of atherosclerotic disease that people should be aware of. [00:13:09] Ken asks Vyvyane how she would characterize the significance of the tunica intima of the coronary artery. [00:15:25] Ken asks about the third recent anatomical highlight to blood vessels relevant to the discussion. [00:19:19] Ken follows up, asking if this is how the vasa vasorum contributes to our understanding of the development of atherosclerosis. [00:21:05] Ken asks Vyvyane to explain what endothelial dysfunction is and what are its downstream effects. [00:26:09] Ken asks Vyvyane to expound on the link between atherosclerotic disease and auto-immunity. [00:31:01] Ken asks, given the link to inflammation, if there have been any therapeutic developments made in the treatment of atherosclerotic disease. [00:34:54] Ken asks about the vaccine that is being developed for atherosclerosis. [00:37:53] Ken mentions that another recent development in the field is the growing appreciation for clonal hematopoiesis in atherosclerosis. Ken asks Vyvyane to explain what clonal hematopoiesis is. [00:39:55] Ken asks Vyvyane what some actionable takeaways are from our discussion on atherosclerosis that listeners can take home with them. [00:43:17] Ken asks Vyvyane about her passion for dance, and how much time she invests in that area of her life. [00:48:11] Ken follows up asking Vyvyane what drives her to pursue dance so passionately. [00:53:34] In closing the interview, Ken encourages listeners to check out Vyvyane’s podcast as well as her website. Links: Vyvyane Loh website Vlmdrounds.com Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page

Today we have Dr. Johnathan Edwards, an anesthesiologist and medical practitioner who specializes in human health and optimization. He is perhaps best known for treating mental health conditions with ketamine,  a dissociative anesthetic that is used for general anesthesia, pain relief, depression and epilepsy. John also uses ketamine to help adolescents overcome depression and suicidal ideation. In today’s interview, we talk about his new book, “The Revolutionary Ketamine: The Safe Drug That Effectively Treats Depression and Prevents Suicide.” More Americans have died from suicide than all the wars since Vietnam. The suicide rate among 10- to-24-year-olds in this country increased 62 percent from 2007 through 2021. As John points out in today’s discussion, most people are not aware that American children between the ages of 10 and 14 are twice as likely to die from suicide than homicide. Show notes: [00:02:39] Dawn explains that suicide is a pressing problem in America, with more Americans dying of suicide than from all the wars since Vietnam. She also points out that police and firefighters are more likely to die from suicide than in the line of duty. John then gives an overview of ketamine and its ability to help treat depression and suicidal thoughts. [00:06:56] Dawn pivots to mention the dark side of ketamine, including ketamine misuse and overdose.  Recent studies have reported a worldwide increase in ketamine misuse and overdoses. Back in October, Mathew Perry, one of the stars of the popular sit-com “Friends,” died from what the Los Angeles cororner described as the acute effects of ketamine. Because this was such a high-profile case, Dawn asks John to discuss the potential adverse effects of ketamine. [00:13:03] Ken mentions a 2022 study in the American Journal of Drug and Alcohol Abuse that looked at ketamine overdoses and deaths. The study found no cases of overdose or death from ketamine used in a clinical setting as therapy for depression. Ken asks if there is anything John would like to add about ketamine and safety. [00:13:059] Dawn shifts to talk about John’s background, mentioning that he grew up riding dirt bikes and eventually raced bikes professionally. [00:15:18] Ken asks John to share his story of how a junior college professor sparked his interest in science. [00:17:49] Dawn mentions that John jumped around from Eastern Virginia Medical School, to the University of Reno, to the University of Utah, at which point it looked as though he was heading for a career in internal medicine. Dawn asks why John changed his mind and decided not to pursue that career path. [00:19:40] Dawn asks John what led him to the University of South Florida. [00:20:18] Ken asks John about another career shift that came about as the result of a suggestion from one of John’s professors. [00:21:42] Dawn asks about John’s motivation to move to Las Vegas to be close to his father. [00:22:59] Dawn asks John to explain what motivated him and his wife to move to France after their daughter turned five. [00:24:55] Dawn asks John to talk about the transition of ketamine from anesthetic to antidepressant. [00:28:16] In his book on ketamine, John writes about how the benefits of supervised psychedelic therapy can be broken down into four effects. Ken asks John to briefly explain each of these effects. [00:31:39] Dawn asks John to explain how ketamine manipulates the function of brain receptors as an antagonist and agonist. [00:33:40] Dawn mentions that some people do not believe that ketamine functions as a classic psychedelic like psylocibin or LSD. She asks John if he agrees. [00:35:54] Ken mentions a recent STEM-Talk interview with Mark Mattson discussing glutamate. In Mark’s book, “Sculptor and Destroyer: Tales of Glutamate,” he points out that ketamine’s highest interactions are with glutamate, and this affinity has been shown to alleviate depression and schizophrenia. Ken asks John to discuss the significance of ketamine with respect to its ability to increase glutamate. [00:38:45] Dawn asks John to talk about MDMA, which is another non-classical psychedelic that has medicinal properties, particularly in the treatment of PTSD. [00:40:48] Ken brings up STEM-Talk’s interview with Rachel Yehuda in episode 101, whose research has revolutionized our understanding of PTSD. In John’s book he mentions that we have historically not been very good at the complex task of treating PTSD, which Rachel also echoed in her interview. Ken explains that a key problem, historically, has been the stigma associated with psychedelics, and he asks John if he thinks that this stigma is lessening in light of the numerous positive findings on the use of psychedelics to treat PTSD. [00:44:34] Ken explains that inflammation and suicide are closely linked, and while the mechanisms whereby ketamine acts as an anti-suicidal drug are somewhat unclear, there is emerging evidence that ketamine is an anti-inflammatory agent. Ken asks John to talk about this. [00:47:11] Ken asks what John’s take is on the evidence that whales might also engage in suicidal behavior. [00:49:35] Dawn asks John to talk about the important point that ketamine and other medications are far less effective in treating mental health disorders when not coupled with psychotherapy. [00:52:07] Ken explains that following the institution of COVID lockdowns, drug overdoses in America increased substantially from previous years. Ken asks John to give his insight on this increase. [00:55:07] Ken asks John about those individuals who should not be on ketamine, mentioning people suffering from mania and schizophrenia, and asks if there are other groups that should steer clear of ketamine. [00:56:57] Ken asks if ketamine is effective in treating chronic pain. [00:58:38] Dawn closes the interview asking about John’s experience traveling the world for the Dakar Rally, which is an off-road endurance event. Dawn also mentions that the rally will be the topic of John’s next book. Links: Johnathan Edwards bio Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio

What if the path to delaying the onset of dementia symptoms begins at the nose? It is a doorway that the research of Dr. Michael Leon opened with a 2023 study on the power of olfaction enrichment to influence memory function and brain health. The findings drew wide acclaim and interest when his results found that stimulation of our sense of smell with essential oils had a profound impact on memory, cognition, and language recall. Our conversation with Leon on STEM-Talk Episode 164 is available now wherever you enjoy podcasts. Leon’s long research career has focused on the influence of environmental enrichment on neurological function, disease, and disorders. He has studied the benefits of sensory-motor stimulation for children with autism spectrum disorder, for the treatment of anorexia and for those with dementia and neurological conditions. He is a professor emeritus in the Department of Neurobiology and Behavior at the University of California Irvine, where his Leon Lab has focused on studying the benefits of increased sensory-motor activity in children with autism spectrum disorder. The work that the Leon Lab is doing is fascinating, and the applications this olfaction stimulation study are potentially important and wide-reaching. Overview: [00:02:33] Dawn starts the interview by asking Michael how he got interested in science. [00:003:59] Dawn asks how Michael got involved in studying olfaction. [00:04:36] Dawn asks about Michael’s research on Autism Spectrum Disorder (ASD), which resulted in a series of studies from 2013, 2015, and 2016. [00:08:11] Dawn asks how Michael took the principles of environmental enrichment from his work on autism and applied them to his aging research, which began in 2018. [00:09:28] Ken asks Michael about his 2023 study titled “Olfactory enrichment using an odorant diffuser improves memory and modifies the uncinate fasciculus in older adults.” [00:11:25] Ken asks Michael why he chose the specific seven odors that he used in the study. [00:12:24] Ken poses a listener question about whether or not a CPAP machine, which many older Americans use, would complicate Michael’s olfactory enrichment protocol, or if it is possible that the CPAP machine and the protocol can be used together. [00:13:35] Dawn asks Michael what the selection and recruitment process was like for this study. [00:14:48] Ken asks, in light of Michael’s research on the connection between memory and olfaction, what the potential consequences might be for people who reported loss or diminishing sense of smell following a COVID-19 infection. [00:16:51] Ken asks if any of the olfactory remediation kits have shown promise in restoring lost olfaction following COVID-19. [00:17:32] Ken asks what the mechanism is behind the loss of olfaction following menopause. [00:19:43] Dawn asks Michael how his olfactory enrichment as a memory intervention compares to other memory interventions like dancing, music and audio books. [00:20:22] Ken asks Michael what the limitations of the study were, as well as what kind of follow up he is planning. [00:23:14] Ken asks if there is any promise in applying Michael’s olfactory therapy to mild TBI. [00:24:10] Dawn asks Michael to describe how the brain processes information while asleep versus while awake, and if this influenced his study. [00:25:53] Dawn mentions that the participants of Michael’s 2023 study were healthy, with no signs of dementia. She then asks Michael if he can speak to the potential use of olfactory enrichment for adults living with a dementia diagnosis. [00:26:41] Ken asks if this olfactory enrichment approach is efficacious for Alzheimer’s and other forms of dementia. [00:27:10] Ken mentions the difficulty in treating Alzheimer’s pharmacologically due to the varied causes of the disease among individuals. [00:29:10] Ken asks Michael if there are environmental protocols other than olfactory enrichment that seem promising for preventing age-related memory decline. [00:30:22] Ken mentions that while Michael’s olfactory enrichment does not cure dementia, it can slow its progression and even prevent symptoms from being expressed. Ken goes on to say that Michael’s paper had a hugely positive reaction. [00:31:24] Ken asks about Michael’s plans to develop a CPAP and BIPAP version of his Memory Air device. [00:32:21] Ken mentions that the positive response to Michael’s paper is probably because it is an effective approach that does not ask a lot of the person using it. [00:33:24] Dawn asks if Michael thinks that the common notion that olfaction is the least important sense is misguided. [00:34:18] Dawn asks Michael what is next for him and his team. Study links: Environmental Enrichment as an Effective Treatment for Autism, 2013, Behavioral Neuroscience, https://psycnet.apa.org/record/2013-17639-001 Environmental Enrichment as a Therapy for Autism: clinical trial replication and extension, 2015, Behavioral Neuroscience. https://pubmed.ncbi.nlm.nih.gov/26052790/ Environmental Enrichment Therapy for Autism: Outcomes with Increased Access, 2016, Neural Plasticity, https://pubmed.ncbi.nlm.nih.gov/27721995/ Environmental Enrichment and Successful Aging, 2018, Frontiers in Behavioral Neuroscience, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065351/ Olfactory loss is a predisposing factor for depression, while olfactory enrichment is an effective treatment for depression, 2022, Frontiers in Neuroscience. https://pubmed.ncbi.nlm.nih.gov/36248633/ Overnight olfactory enrichment using an odorant diffuser improves memory and modifies the uncinate fasciculus in older adults, 2023, Frontiers in Neuroscience. https://www.frontiersin.org/articles/10.3389/fnins.2023.1200448/full LINKS: Michael Leon bio Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio

Today we have Dr. Mark Mattson, an adjunct professor of neuroscience at Johns Hopkins School of Medicine who is making his third appearance on STEM-Talk. Today’s interview focuses on Mark’s research into glutamate and comes on the heels of the publication of Mark’s new book, “Sculptor and Destroyer: Tales of Glutamate – The Brain’s Most Important Neurotransmitter.” Today Mark explains how more than 90 percent of the neurons in the brain deploy the little-known molecule glutamate as their neurotransmitter. Glutamate controls the structure and function of the brain’s neuronal networks and mediates many of our human capabilities, such as learning, memory, creativity, and imagination. But there’s also a dark side to glutamate. Mark shares how it can play a causal role in the development of disorders such as autism, schizophrenia, and epilepsy as well as diseases such as Alzheimer’s, Parkinson’s, and ALS. Mark is affectionally known as the godfather of intermittent fasting and his first appearance on STEM-Talk focused on the many ways that fasting optimizes healthspan and even lifespan. His second STEM-Talk interview followed the publication of his book, “The Intermittent Fasting Revolution: The Science of Optimizing Health and Enhancing Performance.” Show Notes: [00:04:05] Dawn welcomes Mark back to STEM-Talk for his third appearance. Dawn mentions that our previous two episodes with mark focused on intermittent fasting, and that Mark is considered the godfather of intermittent fasting. Dawn goes on to mention that the National Institutes of Health has described Mark as “one of the world’s top experts on the potential cognitive and physical health benefits of intermittent fasting.” [00:05:05] Ken mentions that in our previous STEM-TALK interview Mark shared that he was working on a new book about glutamate. Ken adds that Mark considers his research on glutamate to be his most important work. Ken asks why Mark feels as though this research is his most important, given his substantial contributions in other areas. [00:05:49] Dawn mentions that Mark’s research hasn’t been limited to just glutamate and intermittent fasting. Mark has contributed to a broad range of topics including brain evolution, cognition, the impact of diet and lifestyle on brain health, as well as the pathogenesis and treatment of various neurological conditions. Dawn asks Mark to talk about his motivation to understand how the pieces of the “brain puzzle” fit together, which is the core motivation for his pursuing a broad scope of research. [00:07:22] Ken asks about Mark’s postdoc work, where he discovered that glutamate sculpts the formation of hippocampal neuronal networks during development. [00:09:33] Ken mentions that while Mark was at the University of Kentucky, he discovered that the amyloid beta peptide which accumulates in the brain during Alzheimer’s disease renders neurons vulnerable to excitotoxicity. Ken goes on to say that since this, and the previously mentioned discovery, neurologists have shown that neuronal network hyperexcitability occurs early in Alzheimer’s and may contribute to neuronal degeneration. Ken asks Mark to talk about the significance of these two discoveries. [00:13:39] Dawn asks Mark to talk about the significance of glutamate as a molecule and how it controls the formation of nerve cell networks as the brain develops in utero. [00:17:50] Ken asks Mark why he thinks that glutamate rarely comes up in discussions of neurotransmitters, despite its importance of its functions. [00:19:58] Ken asks Mark to expound on the “dark side” of glutamate. [00:26:04] Dawn mentions that we may never know where in the universe glutamate originated, and while it might have been here on Earth, it perhaps originated somewhere else in the universe. Dawn asks Mark to expand on that notion. [00:28:33] Ken shifts to the history of glutamate research, explaining that up until the 1940’s, researchers largely ignored the possibility that glutamate was a neurotransmitter. But then a Japanese professor during WWII demonstrated that glutamate could excite neurons. Ken asks Mark to discuss the significance of this finding. [00:31:44] Ken explains that the brain, while only comprising two percent of body weight, utilizes 20 percent of the body’s energy output, roughly 400 calories in a 24-hour period. Ken asks Mark to explain the role that glutamate plays in the utilization of energy in the brain. [00:33:32] Dawn mentions that in the first half of Mark’s book, he explains how glutamate controls the structure of neuronal networks in the brain, and how it plays a role in not only mediating the brain’s ability to learn and memorize, but also contributes to inspiring creativity and imagination. Dawn asks Mark to discuss the essential role that glutamate plays in our lives. [00:41:04] Dawn mentions that the later chapters of Mark’s book delve into the “dark side” of glutamate, and how subtle aberrancies in the activity of neurons that deploy glutamate can result in behavioral disorders like autism, schizophrenia, chronic anxiety and depression. With the primary focus of this section of the book being how glutamate can overly excite neurons to the point of leading to a wide range of disorders like epilepsy, Alzheimer’s, Parkinson’s, ALS and even Huntington’s. Dawn asks Mark to explain how aberrant glutamatergic neurotransmission is a fundamental feature of so many different neurological disorders. [00:47:22] Ken asks what the role of aging is in making neurons more vulnerable to excitotoxicity over time. [00:51:07] Ken asks about the relationship between brain aging and glutamate. [00:52:16] Ken asks Mark about a 2018 paper he wrote which discussed how the incidence of seizures is higher in older adults than in middle-aged adults. Ken asks Mark to explain how some of the features of the aging brain can stimulate the development of seizures. [00:55:39] Ken mentions that at IHMC, we work with military populations that have suffered traumatic brain injury. Ken asks Mark to explain how glutamate leaks out following a TBI and the effects that has. [00:57:26] Dawn mentions the chapter in Mark’s book titled “Eve of Destruction,” which explores the role of glutamate in Alzheimer’s, Parkinson’s and other neurodegenerative conditions. Dawn goes on to mention that on3 in every three people over the age of 65 will die with Alzheimer’s, and asks Mark to describe the symptoms of this disease and how it leads to the inexorable decline in the ability to remember experiences. [01:03:52] Ken mentions that Mark has been quoted as saying that everyone is at risk for Alzheimer’s disease, not just certain populations, and asks why that is. [01:07:15] Ken asks Mark to give a high-level overview of the research that suggests that ketone esters may benefit people at risk of cognitive impairment and Alzheimer’s. [01:12:33] Dawn praises Mark’s new book, as well as his work on glutamate over the years. He asks Mark how he feels now that the book is published. [01:14:21] Ken asks Mark how his recovery from his bicycle accident is going and if he has returned to cycling. Links: Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio Mark Mattson bio

Today we have Dr. Marc Hamilton, an international expert in muscle physiology. He has published pioneering work on the soleus push-up, a potent physiological method which Marc discovered having the ability to elevate metabolism for hours, even while sitting. As a professor of Health and Human Performance at the University of Houston, Marc’s research focuses on solving problems of metabolism and biochemistry. His lab currently has a number of ongoing investigations, including studies on the biochemical mechanisms that may optimize fat metabolism to fuel muscle when fasting between meals.  This research includes a look at maximizing glucose metabolism while also reducing related plasma hyperinsulinemia due to chronic inflammation and carbohydrate ingestion. Another recent area of research focus has been to improve metabolic health for preventing diabetes and pre-diabetes. This includes the goal of improving glucose tolerance. Research has shown that glucose intolerance has been a particularly troubling metabolic problem and has proven to be more difficult to treat than most people realize. Marc is also well known for a string of papers beginning in early 2000’s that found excessive sitting should be viewed as a serious health hazard. This research illuminated how metabolic and biochemical processes are significantly impacted by certain types of prolonged muscular activity and inactivity. In today’s interview, we particularly talk to Marc about his paper in iScience that reported that the soleus push-up’s ability to sustain elevated oxidative metabolism to improve the regulation of blood glucose is more effective than many popular methods currently touted as a solution. Show notes: [00:02:48] Marc begins the interview talking about his childhood and growing up outside of Houston. [00:03:49] Ken asks if Marc’s later affinity for the real-world scientific problems that he works on today was originally inspired, in part, by his childhood history of hunting and studying animal behavior and anatomy. [00:05:20] Marcas asks Marc what other hobbies he had as a child. [00:06:35] Marcas mentions that Marc didn’t go to college with the intention of becoming a scientist and asks Marc what he had in mind when he started his undergraduate studies at the University of Texas. [00:09:08] Marcas asks Marc if there was anything in particular in his zoology undergrad that sparked an interest in pursuing a master’s degree in exercise physiology. [00:10:15] Marcas asks Marc to talk about what he enjoyed the most about graduate school, particularly with his Ph.D. at the University of South Carolina. [00:16:05] Ken asks if Marc had a great deal of independence with his PhD. [00:17:27] Ken mentions that Marc went to the University of Texas School of Medicine in Houston for his postdoc research, which focused on physiology, cell biology, and pharmacology. Ken asks Marc what that time was like. [00:19:45] Ken asks Marc to talk about some fundamentals of muscle metabolism that listeners should keep in mind before diving deeper into his current research. [00:24:58] Marcas shifts to talk about Marc’s 2004 paper “Exercise Physiology vs Inactivity Physiology,” which focused on the enzyme lipoprotein lipase (LPL) and how periods of inactivity impact its regulation. [00:32:05] Ken mentions that Marc published a string of papers after his previously mentioned 2004 paper, elaborating on the same theme. Ken brings up his 2008 paper, titled “Too Little Exercise and Too Much Sitting,” in particular. Ken asks Marc to talk about his conclusion in that paper, that excessive sitting should be viewed as a serious health hazard. Ken also asks Marc if there is any efficacy to standing desks and balance boards that one sees in many workplaces now. [00:36:48] Marcas wonders if over the course of Marc’s research if he has seen any differences in the effects of inactivity across the sexes and asks Marc if the effects are roughly equivalent for men and women. [00:39:15] Marcas asks Marc what his opinion is on the movement to have benchmarks and reminders built into most smartwatches, considering that these goals aren’t very personalized. [00:42:27] Marcas shifts to talk about Marc’s 2014 paper “Sedentary Behavior is a Mediator for Type 2 Diabetes,” which looked at the use of moderate to vigorous physical activity, as typically recommended to mediate type-2 diabetes, but found that this did not fully counter the negative effects of too much sitting. Marcas asks Marc to explain why the metabolism in a slow-twitch oxidative muscle is so key in this respect for understanding the healthy response to load or moderate activity. [00:49:11] Ken shifts to discuss Marc’s 2022 article, titled “A Potent Physiological Method to Magnify and Sustain Soleus Oxidative Metabolism Improves Glucose and Lipid Regulation,” in which Marc introduces the idea of a soleus push-up. Ken asks Marc to give an overview of the soleus muscle and what proper activation of it looks like for achieving the potent benefits described in the paper. [00:55:32] Marcas asks about the design of the study, both with respect to the characteristics of the participants, as well as the research protocol. [00:59:43] Marcas asks how many contractions per minute can be expected when doing the soleus push-up correctly. [01:01:06] Ken asks Marc to briefly describe the primary findings of the paper. [01:05:38] Ken asks if there were any findings from that study that Marc really didn’t expect and hadn’t hypothesized. [01:07:10] Marcas explains that even though, on average, the soleus muscle is about 80 to 90 percent type 1 muscle fiber, there are differences in the ratio of composition across individuals. Given this, Marcas asks whether or not Marc has observed any individual differences between the participants’ responses from the muscle biopsies. [01:08:23] Since higher intensity exercise has lower energy economy and thus a higher metabolic boost both during exercise and during recovery, Marcas asks if Marc considered it to be an alternative to the sitting soleus push-up. [01:10:13] Marcas reiterated the importance of not viewing the soleus push-up as a replacement for other forms of exercise. [01:15:04] Ken asks Marc to explain how one performs a soleus push-up properly. [01:19:36] Ken mentions that the soleus push-up could be useful for people who often embark on long airline flights. [01:25:19] Ken follows up the discussion of Marc’s study on the soleus push-up by asking about his more recent study which also generated a lot of interest. [01:36:12] Marcas closes the interview asking Marc about an upcoming bow- hunting trip. Links: Marc Hamilton bio Hamilton lab’s YouTube channel Hamilton lab’s website about the soleus push-up Free copy of one original scientific article in the journal iScience (Cell Press). Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio

Today our guest is Dr. JoAnn Manson, an endocrinologist, epidemiologist, and Principal Investigator of several research studies, including the landmark Women’s Health Initiative. She is a highly cited researcher and was one of the physicians featured in the National Library of Medicine’s exhibition, History of American Women Physicians. Her primary research interests include clinical prevention trials of nutritional and lifestyle factors related to heart disease, diabetes, and cancer and the role of endogenous and exogenous estrogens as determinants of chronic disease. Show notes: [00:02:53] Dawn kicks off the interview by asking JoAnn what it was that drew her to endocrinology. [00:04:33] Ken asks how the things JoAnn witnessed in her early medical practice influenced her interest in disease prevention. [00:05:51] Dawn asks JoAnn to discuss how her mother, who suffered from ovarian cancer, influenced JoAnn’s focus on women’s health. [00:06:40] Dawn asks JoAnn what prompted her interest in clinical research. [00:08:06] Noting the difference between public health and laboratory medical research, Dawn asks JoAnn what the most valuable thing is that she learned from her master’s and Ph.D. work in public health at Harvard. [00:09:10] Ken mentions that while JoAnn and many others are interested in the prevention of disease, our healthcare system does not seem focused on prevention. Ken goes on to asks if this was part of what led JoAnn to work on the Nurses’ Health Study. [00:10:17] Ken asks JoAnn to give an overview of the Nurses’ Health Study for listeners who may not be familiar. [00:11:41] Dawn explains that the Nurses’ Health Study found that women taking hormone therapy had a lower risk of heart disease and a reduction in all-cause mortality. Dawn asks JoAnn to talk about this finding. [00:15:00] Ken asks JoAnn what the impact of the Nurses’ Study has been on public health and women’s health in general. [00:16:29] Dawn asks JoAnn about her experience being a principal investigator in the Women’s Health Initiative starting in 1993. [00:18:17] Ken asks JoAnn to give context regarding how the Women’s Health Initiative (WHI) was designed, how the women were recruited, and what the specific questions were that the study aimed to answer. [00:21:34] Dawn mentions that the three interventions that were evaluated in the WHI were hormone therapy; calcium and vitamin D supplementation; and a low-fat diet. Dawn starts by asking JoAnn about the hormone therapy interventions, and how it was decided which hormone therapies to test. [00:24:25] Dawn asks JoAnn to give some context to the finding from the WHI that women taking the combination of conjugated estrogen and medroxyprogesterone acetate had higher risks of breast cancer and stroke. [00:27:01] Ken asks if the worse outcomes from hormone therapy for older women was due to their advanced age, or the hormone therapy itself. [00:30:25] Ken asks JoAnn to talk about the risk factors for breast cancer that were uncovered by the WHI. [00:35:38] Dawn explains that because of the WHI’s findings, it is more common to use transdermal estradiol, as opposed to the oral form evaluated in the original trial. Dawn asks JoAnn to explain how the different ways these hormone formulations are processed in the body affects the risk benefit ratio. [00:39:04] Dawn asks if these transdermal estradiol treatments might have benefits regarding cognitive decline. [00:43:26] Ken asks JoAnn for her thoughts on the overuse and potential misuse of the term ‘bioidentical hormones.’ Ken goes on to note that the term has seemingly become more related to marketing and further distanced from clinical science. [00:46:48] Dawn asks JoAnn to talk about the role that perimenopausal birth control decisions can play in the management of hot flashes for women in their 40s and 50s. [00:49:14] Ken shifts the conversation to discuss the second pillar of the WHI, calcium and vitamin D supplementation. Ken explains that this pillar of the trial tested to see if this supplementation decreased risk of hip fractures in post-menopausal women. Ken asks JoAnn to discuss these findings. [00:53:13] Dawn asks about the third pillar of the WHI, which looked at whether a low-fat dietary pattern reduced the risk of breast cancer, colorectal cancer, or coronary heart disease. [00:55:31] Dawn asks JoAnn what questions are left for the WHI to explore. [01:00:17] Ken asks about a recent report in the journal Menopause, which looked at the cognitive effects of clinical menopausal symptoms. [01:01:36] Dawn asks JoAnn to expound on what ‘cognitive decline’ is measured as, with respect to sleep loss resulting from menopausal symptoms such as hot flashes and night sweats. [01:02:38] Dawn asks JoAnn about a study she and her colleagues conducted at Brigham showing that a comprehensive multivitamin can delay age related memory decline by an average of two years. [01:06:41] Ken asks about the findings of JoAnn’s 2018 study in The New England Journal of Medicine, which looked at whether vitamin D supplementation resulted in a lower incidence of invasive cancers and cardiovascular events. [01:10:11] Regarding the aforementioned study, Ken explains that a subgroup analysis raised the possibility of differential effects of cancer incidence connected to BMI. Ken asks JoAnn to elaborate on this subgroup analysis. [01:13:41] Ken asks if the aforementioned results would look more pronounced, or different in some way, if the data was analyzed with respect to body composition as opposed to BMI. [01:15:09] Dawn asks JoAnn what she would like to see change about how women’s health is taught and studied with respect to perimenopause, menopause, and post-menopause. [01:16:13] Dawn asks JoAnn what she and her colleagues plan to investigate next, and what answers she thinks we will have for future generations of women as they age that we don’t have now. [01:18:13] Ken wraps up our interview asking JoAnn what she likes to do in her spare time. Links: JoAnn Manson bio Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio

Today we have Dr. Hans Van Dongen, director of the Sleep and Performance Research Center at Washington State University in Spokane. Dr. Kevin Gluck, a senior research scientist at IHMC, joins Dr. Ken Ford to interview Hans about his studies on inter-individual differences in vulnerability to fatigue as well as the cumulative cognitive deficits that follow chronic sleep restriction. Hans is known for his mathematical modeling of fatigue’s effects on performance. At the Sleep and Performance Research Center, Hans and his colleagues investigate how sleep loss and circadian misalignment impact brain function, cognition and behavior. Show notes: [00:02:50] Kevin opens the interview by asking Hans about his childhood growing up in The Netherlands. [00:03:23] Ken asks Hans what he was like as a kid. [00:03:50] Kevin mentions Hans’s father was a math and science teacher and wonders if that influenced Hans’ interest in science. [00:04:48] Hans talks about attending Leiden University and explains why he majored in astrophysics. [00:06:09] Hans shares how working in a psychophysiology lab put him on a path to specialize in sleep research. [00:08:00] Hans talks about how he was part of a study that proved the morning-evening chronotype was a biological trait, rather than a psychological one. [00:09:55] Ken asks Hans what led him to take a post-doc position at the University of Pennsylvania. [00:11:22] Hans explains what led him to move from the University of Pennsylvania to Washington State University. [00:13:36] Ken mentions that The Sleep and Performance Research Center, where Hans serves as the director, is a coalition of basic and applied research laboratories that aim to understand the neurobiology of sleep and sleep loss. Ken goes on to mention that Hans and his colleagues investigate sleep and biological rhythms, and their impact on health and performance. Kevin asks Hans to give an overview of what sleep loss is and the effect it has on our metabolism, immune system, and cognitive performance. [00:15:57] Kevin mentions Hans’ recent paper which investigated how circadian misalignment due to night shift work has been associated with an elevated risk of chronic disease. The paper demonstrated that just a few days of being on a night shift schedule throws off protein rhythms related to blood glucose regulation, energy metabolism, and inflammation. Kevin asks Hans to talk more about the findings. [00:21:18] Ken asks how long it takes for a person’s circadian rhythm to normalize after ceasing to work night shifts. [00:22:13] Kevin brings up Hans’ paper on the continually operating neurobiological mechanisms of homeostatic and circadian processes and their effects on neurobehavioral performance. Before asking about the paper itself, Kevin asks Hans to give an overview of the homeostatic process and its relationship to the circadian process. [00:24:14] Ken notes that the bio-behavioral function and evolutionary advantage of the circadian process is widely recognized, but that the neurobiology of the homeostatic process and its effects on performance are still poorly understood. In a 2011 paper, Hans attempted to shed light on the underlying mechanisms of the homeostatic process to provide an explanation for why the buildup of homeostatic pressure resulting from sleep loss leads to instability in vigilant attention. To explore this, Hans first explored the time-on-task effect. Ken asks Hans to explain the time-on-task effect and its role in cognitive performance. [00:27:06] Kevin brings up the “local sleep hypothesis,” which attempts to explain the time-on-task effect. According to the local sleep hypothesis, groups of neurons involved in performing a task will “fall asleep” as a homeostatic consequence of sustained use, which leads to an interruption in information processing, leading to impaired performance. Kevin asks Hans what empirical and scientific evidence exists for the hypothesis. [00:32:03] Ken explains that working all hours of the day and suffering chronic sleep restriction, and at times sleep deprivation, has become normalized in our society. In light of this, Ken asks what impacts sleep deprivation and sleep restriction have on the cognitive performance and overall health. [00:34:02] Ken asks Hans to elaborate on the fact that sleep deprivation is particularly problematic and potent with regards to decision-making when circumstances are uncertain or unexpected. [00:38:40] Ken asks Hans what his thoughts are on stimulant use for workers and operators who need to stay awake for extended periods. [00:41:43] Hans discusses how contrary to popular belief, even modest amounts of sleep loss can have negative impacts on cognitive and physical performance. [00:46:40] Kevin asks Hans about the common belief that people can adapt to chronic sleep restriction. [00:49:29] Hans describes his work with the Psychomotor Vigilance Test (PVT), which requires participants to respond as quickly as possible to a stimulus that appears at random intervals. [00:52:46] Kevin mentions that Hans published a review paper in 2019 with Amanda Hudson and Kimberly Han in Neuropsychopharmacology. This paper points out that research on sleep deprivation, vigilant attention, and brain function may help determine the fixed connections and malleable connections between specific neuronal pathways involved in specific cognitive processes. [00:56:22] Ken mentions that to better understand the neurocognitive effects of sleep deprivation, Hans performed a study that evaluated the strategy of ‘catching up on sleep’ a practice many people engage in during periods where sleep restriction is inevitably followed by abundant free time. Ken asks Hans to discuss the design of this study and its findings. [01:06:41] Kevin pivots back to Hans’ study on sleep restriction and deprivation. According to the study, a person who is chronically sleep deprived experiences diminishing performance, and if that person undergoes sleep deprivation by skipping a night of sleep, their performance further diminishes. However, a person would see their performance recover within a few days of restricted sleep following sleep deprivation. Kevin asks Hans to expand on these findings. [01:10:52] Kevin asks Hans to clarify some terminology regarding sleep health, as well as explain how someone at home can assess their own sleep health. [01:15:13] Ken asks Hans what his sleep schedule is like. [01:19:22] Ken mentions that Hans was recently featured in a news article about the dreaded ‘mid-day slump’ of energy. Ken goes on to explain that while it is commonly believed that the mid-day slump can be attributed to eating lunch, Hans argues that it is the result of a gap between the circadian clock and the homeostatic clock as a result of inadequate sleep. Ken asks Hans to elaborate. [01:23:36] Ken asks if Hans thinks that the poor metabolic health of many people in North America also contributes to the mid-day slump. [01:25:19] Ken asks Hans to think of the biggest lessons he has learned about science and life during his career. [01:29:14] Kevin mentions that Hans and his wife enjoy traveling together, but that his wife has a bit of a complaint about these travels. [01:30:59] Following up on the topic of travel, Ken asks Hans how he manages jet lag. [01:34:56] Ken recommends for listeners, an app called Timeshifter for managing jet lag. [01:35:04] Ken, Kevin and Hans wrap up the interview talking about jet lag. Links: Hans Van Dongen Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Kevin Gluck bio