Today Dr. David LeMay steps in to co-host with Dr. Ken Ford for our interview with Dr. Charles Serhan. Charles is a Harvard professor best known for his discovery of specialized pro-resolving mediators. SPMs are molecules that can activate the natural resolution of inflammation and help people avoid anti-inflammatory drugs. The discovery of SPMs spurred a paradigm shift in our understanding of inflammation and human disease.

Charles is the Simon Gelman Professor of Anesthesia at Harvard Medical School and the director of the Center for Experimental Therapeutics and Reperfusion Injury at Brigham and Women’s Hospital. He also is a co-director of the Brigham Research Institute.

David, who was our guest on Episode 69 of STEM-Talk, is a sports medicine and rehabilitation physician with a Pensacola, Florida practice that focuses on lifestyle and performance medicine. He also is a visiting research scientist here at IHMC.

Show notes

[00:03:33] David opens the interview mentioning that Charles grew up in New York City with a passion for music. David explains that Charles learned to play the vibraphone in junior high and played professionally for a year before going to college. David asks Charles why he decided to pursue science instead of music.

[00:04:22] Ken asks Charles what kind of vibraphone he plays.

[00:06:02] Ken asks, aside from the desire to help people, if there was something particular about studying science that Charles really enjoyed.

[00:06:45] David asks about Charles’ experience at the State University of New York at Stonybrook studying biochemistry and immunohistochemistry.

[00:07:16] David asks if there was any carry over of skills for Charles from his career in music to his career in science.

[00:08:16] Ken mentions that after Charles earned his bachelor’s degree, one of his professors persuaded him to go to New York University for a master’s and Ph.D. Ken also mentions that at the time Charles worked in the lab of Gerald Wiseman at Woods Hole Marine Biological Laboratory and asks about that experience.

[00:12:37] David asks if this experience led Charles to a focus on neutrophil membrane remodeling for his Ph.D.

[00:13:59] David asks Charles if it was at the Karolinska Institute where he met his future wife.

[00:14:38] Ken asks Charles about one of his mentors, Michael Heidelberg, who gave Charles advice about how to be a good scientist.

[00:17:13] David explains that in the 1990’s Charles discovered Specialized Pro-Resolution Mediators and has since pioneered a new field on the utility of SPMs for a variety of inflammatory diseases.

[00:25:01] Ken backs up to ask Charles what drew him to study inflammation in the first place and how that led him to do more research on the subject than any other scientist.

[00:26:26] David asks Charles to touch on some different types of inflammation that the body experiences.

[00:35:12] Ken asks Charles about how a trip to Asia during which he developed a hole in his intestines, resulted in first-hand experience on the importance of controlling inflammation.

[00:41:00] David asks if Charles was taking any non-steroidal anti-inflammatory medications when he developed peritonitis.

[00:41:53] David asks Charles to explain what non-steroidal anti-inflammatory medications do to the healing process.

[00:45:35] David brings up a recent discovery in animal models that as animals age, their ability to produce resolution mediators declines, possibly contributing to the loss of muscle mass with age.

[00:48:09] Ken asks Charles to talk about the explosion of research into the potential therapeutic applications of SPMs in the treatment of a variety of chronic diseases known to be driven in part by chronic inflammation.

[00:51:06] David asks Charles to explain the differences between resolvins, protectins, and maresins, as well as what role each plays in the healing process.

[00:56:04] Ken mentions a review article that Charles published in 2017 in the Journal of Molecular Aspects of Medicine, which looked at SPMs and their capacity to change pharmacology through resolution physiology.

[01:00:22] David asks Charles to explain the difference between inflammation and resolution.

[01:03:13] Ken asks Charles to give an overview of the research he is currently conducting at the Serhan Laboratory.

[01:05:50] David asks Charles about a paper he published last year in the Proceedings of National Academy of Sciences titled: “Resolvin D1 Prevents Injurious Neutrophil Swarming in Transplanted Lungs.” This provided insights for therapeutically enhancing pro-resolution pathways to minimize early leukocyte mediated tissue injury and promote healing following transplantation.

[01:08:43] David asks Charles if the aforementioned use of Resolvin D1 works for ailments such as ischemic stroke or ischemic myocardium after a cardiac event. Charles brings up a paper by Gabrielle Fredman that explored the use of resolvins to reduce inflammation in atherosclerosis.

[01:13:10] David mentions that Charles has three children, two of whom are in the military and asks for Charles’ thoughts on the use of SPMs in military populations.

[01:17:04] David asks Charles if there might be any protective effects of taking SPMs prior to or during exposure to extreme environments.

[01:17:48] Ken comments on Charles’ use of the phrase “nutritional armor,” coined by Joe Hibbeln. Charles talks about his experience working with Joe over the years.

[01:19:00] Ken recounts an experience when he was a member of the Defense Science Board and invited Joe Hibbeln to present his nutritional armor concept to the Board.

[01:22:05] David mentions that for the sports science world, recovery is a big focus. David asks if resolution is a more appropriate way to approach this issue than traditional anti-inflammatory interventions.

[01:23:33] David follows up asking Charles what the role of sleep is in resolution.

[01:24:57] David shares some of his experience using SPMs in his practice, and Ken mentions his own personal use of SPMs. Charles discusses how SPMs are derived and the importance of supplementation.

[01:31:04] Ken mentions that there were two books that Charles found very influential in his early career, “The Art of Scientific Investigation,” and “Men Like Gods.” Ken asks how these books impacted Charles, and if he still recommends them to young scientists and graduate students.

Links:

Charles Serhan bio

Learn more about IHMC

STEM-Talk homepage

Ken Ford bio

Ken Ford Wikipedia page

David LeMay bio

Dave Feldman is the founder of the Citizen Science Foundation and is known for his research into the ketogenic diet. Dave is a software engineer by training who embraced a ketogenic diet to avoid his progression toward type 2 diabetes. he joins us on this episode of STEM-Talk to share that journey.

After undertaking the high-fat/low-carbohydrate diet, Dave’ LDL cholesterol spiked. Dave used his training as an engineer to start learning everything he could about cholesterol and lipids. What he learned led him to create the website Cholesterol Code, a research hub for information and emerging data on cholesterol, particularly in the context of a low-carbohydrate lifestyle.

Dave’s Citizen Science Foundation is designed to support projects and research that promote collaborative efforts across multiple disciplines, both in and outside formal scientific institutions.

Show notes:

[00:02:53] Dawn opens the interview asking Dave what he was like as a kid.

[00:03:44] Dawn mentions that Dave divided his time as a child between Denver and Wichita due to his parents’ divorce and asks Dave what the best part of his childhood was.

[00:04:28] Ken mentions that Dave has described both his parents as graphic artists and Bohemian, “hippie spirit” types. Ken asks what he learned from them that fueled his interests and goals.

[00:05:46] Ken asks about Dave’s first computer, which was a Commodore 64, as well as his early experience with computers.

[00:08:50] Dawn mentions that Dave’s interest in computers came in a time before the internet and asks what he learned about computing in those days.

[00:10:51] Dawn explains that since Dave grew up in the 1980s, there was not much in the way of computer science curriculum in schools and asks Dave how he supported his interest in programming.

[00:12:33] Ken asks Dave about how self-directed learning has been a theme throughout his whole life.

[00:14:35] Dawn asks Dave about his childhood hobbies, including running and competitive storytelling.

[00:17:01] Ken asks how Dave’s experiences in forensic debate in high school helped his career later in life.

[00:18:56] Dawn mentions that Dave initially attended film school and asks if it is true that Dave’s side hustle of doing contract software work overtook his original plan to graduate.

[00:20:49] Dawn asks about Dave’s experiences working in the game platform development business in Las Vegas, as well as what these experiences taught him.

[00:22:23] Ken asks Dave about a “the piece of paper” that Dave says changed his life in 2015.

[00:28:58] Ken follows up, asking Dave if he checked his LDL-P or his ApoB at the same time as his cholesterol levels.

[00:30:37] Ken mentions that he knows some people that when consuming a ketogenic diet did not see a substantial increase in LDL-C, but did experience a substantial elevation of LDL-P.

[00:35:03] Ken pivots to discuss a paper that Dave and others published in Current Developments in Nutrition in 2022 titled: “Elevated LDL Cholesterol with a Carbohydrate-Restricted Diet: Evidence for Lean Mass Hyper-Responder Phenotype.” Ken asks Dave to describe what it means to be a lean mass hyper-responder.

[00:40:19] Ken mentions his caution against the term lean mass hyper-responder, as it is unclear what “lean mass” refers to in this case. Ken goes on to say that while the lean mass hyper-responder phenotype can be objectively measured in terms of LDL, HDL and triglyceride levels, the lean mass aspect is often measured in these studies with BMI, which is unable to measure body composition. Ken asks Dave what his thoughts are on this and if he would like the possibility of moving away from BMI and towards DEXA scans.

[00:43:37] Ken mentions that Dave’s original article describing the lean mass hyper-responder phenotype has received a lot of response from individuals claiming to fall into that category. While it is difficult to get a precise estimate of the population that fits this phenotype, Ken asks Dave what he thinks the percentage might be.

[00:47:33] Dawn asks about the case report published in Frontiers in Endocrinology in 2022 titled: “Case Report: Hypercholesterolemia, Lean Mass Hyper-Responder Phenotype Presents in the Context of a Low Saturated Fat Carbohydrate-Restricted Diet.” This paper highlights the case of a hyper-responder who adopted a ketogenic diet to manage ulcerative colitis.  

[00:49:38] Ken asks how long the subject of the case report was on an extremely low-carb diet.

[00:50:48] Ken asks Dave, given that cholesterol levels and lipoproteins are remarkably elevated in lean mass hyper-responders, what he thinks the cumulative cardiovascular implications over an extended period might be.

[00:56:19] Dawn turns to discuss Dave’s 2022 paper on the Lipid Energy Model, titled: “Lipid Energy Model: Reimagining Lipoprotein Function in the Context of Carbohydrate Restricted Diets,” asking him to expound on the concept and its significance.

[00:59:02] Ken remarks on the extraordinarily fast review process for this paper on the Lipid Energy Model, explaining that the paper went through submission, review, revision, acceptance and publishing in 30 days.

[01:00:49] Dawn shifts to ask about a 2023 study by Dr. Isabella Cooper in Frontiers in Endocrinology titled: “Thyroid Markers and Body Composition Predict LDL Cholesterol Change in Lean Healthy Women on a Ketogenic Diet: Experimental evidence for the Lipid Energy Model.”

[01:02:48] Ken asks Dave about his journey to self-fund research through crowdfunding, for which he founded a 501c3 non-for-profit, which in 2019 was named the Citizen Science Foundation. Ken asks Dave what challenges he faced in this endeavor.

[01:05:47] Ken asks Dave to describe how he came to partner with the Lundquist institute at UCLA.

[01:08:33] Ken asks what the state of the Citizen Science Foundation is now, and if it has any projects that it is currently funding.

[01:09:57] Ken asks Dave how he sees the foundation evolving in the future and how he would like it to evolve.

[01:11:50] Dawn asks Dave about a study he and his team have just completed on 100 lean mass hyper-responders who received a CT Angiogram to establish baseline coronary artery status, and then a second scan a year later. Dawn asks Dave to discuss the findings of this study in terms of atherosclerotic plaque in the hyper-responder group as compared to the Miami Heart Study group, as well as the overall findings of the study.

[01:17:36] Ken follows up, asking if the results of the aforementioned study will be published soon.

[01:17:54] Dawn asks Dave about the documentary he is working on.

[01:19:53] Dawn closes the interview asking Dave why The Usual Suspects by Brian Singer is his favorite film.

Links:

Dave Feldman 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’s episode of STEM-Talk features Dr. Sten Stray-Gundersen, a post-doctoral research associate at the University of South Carolina who is also an adjunct instructor at the university’s Arnold School of Public Health.

Cohosts Dr. Ken Ford, IHMC’s founder and CEO, and Dr. Marcas Bamman, a Senior Research Scientist at IHMC, talk to Sten about his work on blood-flow restriction training and cardiovascular exercise physiology.

Prior to his position at South Carolina, Sten was a teaching assistant at the University of Texas where he earned his Ph.D.

Sten’s father, Jim Stray-Gundersen, was our guest on episode 34 of STEM-Talk in 2017. Jim, who passed away last year, helped pioneer blood-flow restriction training in the United States.

In today’s interview, we cover the documented benefits of blood-flow restriction and how it not only increases muscle strength, but also improves endurance and reduces the risk of injury. Sten also talks about his research into hypoxia and endothelial function.

Show notes:

[00:03:02] Sten begins the interview talking about the different places where he grew up.

[00:03:32] Marcas asks if it’s true that Sten’s high school soccer team won three straight state titles.

[00:04:06] Marcas mentions that Sten’s younger brother was also a good soccer player in high school, and was on the same team as Sten when they won their third state championship. Sten goes on to talk to talk about playing sports with his siblings.

[00:04:43] Ken mentions that Sten was a nationally ranked speed skater and cross-country skier. Ken asks Sten about other sports he excelled at.

[00:05:45] Marcas asks how Sten’s parents influenced his success in athletics.

[00:06:41] Ken takes time to offer his condolences for the passing of Sten’s father, Jim Stray-Gundersen, who was interviewed on episode 34 of STEM-Talk. The 2017 interview, which focused on blood-flow-restriction training, remains a popular STEM-Talk episode to this day.

[00:08:21] Marcas asks Sten about trying blood-flow restriction (BFR) for the first time with his father.

[00:09:37] Marcas asks Sten what led him to become interested in pursuing a career in science.

[00:10:27] Ken mentions that Sten went to Dartmouth for his undergrad on a soccer scholarship. After graduating, Sten attempted to play in the USL. and Ken asks how that worked out.

[00:11:57] Marcas mentions that as Sten’s injuries from soccer piled up, he began to consider going back to school and pursuing research. Marcas asks what went into that decision-making process.

[00:13:38] Marcas mentions that during Sten’s time in Austin, he worked for a group called ROI Performance, which is an evidence-based physical therapy center that focuses on athletic rehab and performance. Marcas asks Sten to talk about his time there as a BFR specialist.

[00:15:23] Marcas takes a moment to explain that BFR training involves restricting the blood flow to specific muscle groups, using specialized cuffs or bands. Marcas asks Sten to explain how BFR allows people to train with lighter weights while still reaping many of the benefits associated with heavier resistance training.

[00:16:20] Ken mentions that BFR has largely been associated with resistance training, but it is now being looked at in the context of endurance sports. Ken asks Sten to discuss how different protocols of BFR can be implemented to yield different effects in the contexts of resistance training and aerobic training.

[00:19:10] Ken notes that much of the Western research on BFR has now incorporated the arterial occlusion pressure approach, so much so, that it is often promoted as the only safe and effective approach to BFR. Ken goes on to say that this is not how BFR was originally conceived. Ken explains that there are a variety of different approaches to BFR, each with tradeoffs, and asks Sten to discuss these issues in detail.

[00:21:22] Ken mentions that clarity is lacking in much of the BFR literature, and that while some of it is no doubt good research, it’s hard to interpret because of the lack of standardization of protocols and equipment. Ken asks Sten for his thoughts.

[00:22:16] Ken asks Sten to elaborate more on the mechanisms underpinning the benefits of BFR, particularly in the context of resistance training.

[00:24:53] Marcas starts a discussion between Sten and Ken about the current elevated interest in lactate as a stimulant of exerkines, which are hormones, metabolites, proteins, and nucleic acids that are secreted in response to exercise.

[00:28:34] Marcas asks about the different approaches to BFR between an elite athlete looking to gain a fractional advantage, versus a middle-aged or older person aiming to incorporate BFR to improve their health and functionality.

[00:32:15] Marcas pivots to talk about some of the Sten’s studies,  mentioning a paper Sten worked on while he was at Texas that compared the acute cardiovascular responses to two distinct forms of BFR during light-intensity exercise. Marcas goes on to mention that while BFR has become more popular over the last two decades, there have been some concerns raised about the use of BFR in at-risk populations. Marcas asks Sten about those concerns.

[00:38:15] Ken notes that BFR in the form of Kaatsu has been practiced in Japan for more than 30 years with a very low rate of serious complications. Ken mentions that for those listeners interested in Kaatsu, they should listen to Sten’s father’s interview on STEM-Talk episode 34. Ken follows up by asking Sten to give a brief history of Kaatsu.

[00:43:29] Marcas returns to talking about Sten’s previously mentioned study, where Kaatsu bands and wide-ridged cuffs were compared in their effects on the exercise of walking. Marcas asks Sten to explain how they conducted this study and what he and his colleagues found.

[00:44:41] Marcas asks about a 2021 paper that Sten had in the European Journal of Surgical Oncology, where BFR training paired with nutrition was used to improve the physical function of abdominal cancer patients awaiting surgery.

[00:47:53] Ken asks Sten to talk more in-depth about the structure of the previously mentioned study on abdominal cancer patients.

[00:49:32] Marcas explains that ischemic heart disease is the most common form of cardiovascular disease and is a result of the weakening of the heart due to restricted blood flow. This is caused by plaque buildup in the major arteries. Marcas goes on to explain that treatments designed to restore blood flow to the heart can cause ischemia reperfusion injury. Marcas asks Sten to explain what ischemia reperfusion injury entails.

[00:51:16] Marcas explains that Sten was part of a 2022 paper in the journal of applied physiology, which looked at intermittent hypoxia as a potential systemic strategy to prevent the reduction in flow-mediated dilation following ischemia reperfusion injury. Marcas asks Sten to give an overview of what intermittent hypoxia means in this context.

[00:52:49] Marcas explains that Sten’s hypoxic preconditioning had some protective effects during ischemia reperfusion injury and asks Sten to talk more about the significance of this study.

[00:56:26] Ken asks how Sten came to his current post-doc position at the University of South Carolina, in the sports science lab.

[00:57:54] Marcas asks Sten what kind of projects he will undertake in the sports science lab.

[00:58:56] Marcas asks Sten to explain how one can get into BFR training. Sten talks about where to get the specialized cuffs and bands and how to use them.

[01:01:15] Marcas asks about a series of videos Sten did with Kathy Smith, a renowned video workout instructor from the ‘80s and ‘90s. In the video, Sten and Kathy demonstrate the use of the Be Strong BFR bands.

[01:02:17] Ken asks Sten for his thoughts on the use of BFR training to prevent sarcopenia in older adults, especially considering that many seniors have compromised joints and can avoid pain and injury to their joints using lighter weights, while still stimulating an adaptive muscle response with BFR.

[01:03:37] Sten closes the interview discussing some suggested protocols for BFR training.

Links:

Sten Stray-Gundersen bio

Learn more about IHMC

STEM-Talk homepage

Ken Ford bio

Ken Ford Wikipedia page

Dawn Kernagis bio

Our guest today is Dr. Euan Ashley, a pioneer in the use of genomic sequencing to solve some of our most puzzling medical mysteries. Medical genomics, and the precision medicine it will enable, has the potential to predict, prevent, and diagnose many common (and uncommon) diseases.

In today’s interview, we discuss:

— Euan’s work with a colleague who was just the fifth person in the world to have his genome sequenced.

— Precision medicine and how Euan has helped establish medical genomics.

— Technological advances that made sequencing cost-effective for individuals.

— How pathogenic labels will transform healthcare.

— The Undiagnosed Disease Network, which includes physicians from across the country who work with patients and families to solve medical mysteries.

— Research from his lab that shows how all forms of exercise, particularly endurance exercise, confer benefits across all domains of health and function.

Euan is a Scottish-born professor of medicine and genetics at Stanford University. He’s also the author of The Genome Odyssey: Medical Mysteries and the Incredible Quest to Solve Them.

Show notes:

[00:02:27] Dawn begins the interview asking Euan if it is true that he was a computer nerd growing up and if his interest in science fiction played a part in that.

[00:03:03] Dawn asks Euan how he was first introduced to computers and what it was about them that hooked him.

[00:03:44] Dawn asks about Euan developing tax software when he was a teen-ager for his father.

[00:04:53] Ken asks if Euan ever developed, or thought about developing, any computer games.

[00:06:34] Dawn asks Euan where he grew up.

[00:06:51] Dawn mentions that Euan’s father is a physician, and his mother a midwife, and that even from a young age Euan told people that he wanted to become a physician, even though his parents did not push him in that direction. Dawn asks Euan what the underlying pull towards becoming a physician was for him.

[00:07:52] Ken asks Euan how he became interested in data and statistics.

[00:09:08] Dawn mentions that Euan graduated with first-class honors in physiology and medicine from the University of Glasgow, and then went for a medical residency and Ph.D. at the University of Oxford. Dawn asks when in that journey he met his wife Fiona, who helped him through medical school and has played a major role in his life and career.

[00:10:26] Ken mentions that Euan and his wife took off for California, where he conducted his post-doc research at Stanford University. Ken mentions that Euan would later join the Stanford faculty in 2006, and asks Euan what made him decide to move to Stanford in the first place.

[00:12:54] Dawn asks Euan what it was that fascinated him about the heart and at what point did he decide to specialize in cardiology.

[00:15:03] Ken asks Euan when he realized that he could combine his career in medicine with his interests in computing and data.

[00:17:38] Dawn explains that Euan’s lab at Stanford is focused on the science of precision medicine, and that he is perhaps best known for helping to establish the field of medical genomics. Dawn goes on to mention that Euan and his colleagues developed some of the earliest tools for interpretation of the human genome in the context of human health and asks Euan to give a short primer on the genome and how the first draft of the human genome sequence was completed about 20 years ago.

[00:20:36] Ken asks what genomic medicine and precision medicine entail.

[00:22:33] Dawn asks Euan about a moment in his life in 2009 when he walked into the office of a friend who was the fifth person in the world to have his genome sequenced.

[00:27:19] Dawn mentions that in 2010 Euan wrote a paper about Steve, his aforementioned friend who had his genome sequenced. The paper described how Euan put together a team to undertake an integrated analysis of a complete human genome in a clinical context. Dawn explains that this was a groundbreaking paper because it asked the question of how one brings together the entirety of the genetic literature and everything that is known about associations between genes and disease and variants of diseases. Dawn goes on to say that Euan built all these questions into an algorithm that could be deployed in the context of a single patient in a primary-care practice.

[00:30:07] Ken mentions that thanks to technological advancements, it is becoming cost effective to not only sequence individuals, but now to begin investigating entire populations. Ken asks Euan to explain the impact that this might have.

[00:32:14] Dawn mentions that in an interview Euan did with the New England Journal of Medicine’s podcast, he talked about how someday we will see a pathogenic label, or be able to order a pathogenic label, on a genetic report. Dawn explains that current commercial tests can already tell if people are at risk for certain diseases. She mentions that Euan has said more advanced genetic reports are on the horizon and that they will provide even greater detail. Dawn asks Euan to talk about these future genetic reports and pathogenic labels and how they will differ from what we see today.

[00:36:34] Ken mentions that Euan often compares the work of physicians and geneticists to detectives, and that’s because patients often present medical mysteries. Ken asks Euan to elaborate on this and talk about how he teaches young physicians to think of themselves in this way.

[00:39:18] Dawn mentions that about 25 to 30 million Americans have a rare disease, which are sometimes referred to as mystery conditions. She goes on to say that Euan has been instrumental in establishing the Undiagnosed Disease Network, established in 2014, which includes teams of physicians across the country who work with patients and families to solve these medical mysteries. The network has identified scores of previously unknown syndromes to date. Dawn asks Euan to talk about some of this work and how the network came about.

[00:43:36] Ken shifts the conversation to Euan’s recent research. Ken mentions that Euan had a study last year that looked at the impact of genetic sequencing in critical-care settings. Because a genetic diagnosis can improve the prognosis of critically ill patients and therefore guide the clinical management of their care, a lot of effort has gone into developing methods that result in rapid, reliable results. In critical-care situations, decisions need to be made in hours, but traditional testing requires weeks and even rapid testing requires days. Ken goes on to explain that Euan’s paper reported on a new method he and his colleagues developed for rapid sequencing of the whole human genome in patients in as little as five hours. This new ultra-rapid genome sequencing has the potential to lead to significantly faster diagnostics. Ken mentions that this study used a technology called nanopore sequencing and asks Euan to explain what this is and how it works.

[00:46:54] Dawn asks Euan to talk about how the sequence of one of the study’s participants was completed in just five hours and two minutes, setting the Guinness World Record for the fastest DNA sequencing.

[00:52:31] Ken mentions that Euan and other colleagues at Stanford are currently working to cut sequencing time in half from their previous record and asks how far off in the horizon that is.

[00:54:05] Dawn mentions that Euan recently published a paper in Nature that introduced COSMOS (Computational Sorting and Mapping of Single Cells), a cloud-enabled platform that performs real-time cell imaging and analysis. Dawn goes on to explain that COSMOS uses AI and microfluidics to achieve high-throughput imaging that can sort cells using deep morphological assessment. Cell morphology has been used by pathologists and clinicians for years as the gold standard for disease diagnosis and prognosis. Dawn mentions that although there have been technological advances in making single-cell characterization at the genomic, transcriptomic, and proteomic levels, tools for assessing high-dimension cell morphology have not kept pace. Dawn asks Euan to talk about the challenges he and others have faced in performing real-time deep-learning assessment and sorting of cells and how COSMOS helps address these challenges.

[00:58:00] Ken asks about future enhancements of COSMOS, given that Euan is using AI predictions to link machine intelligence to cell biology. Ken asks Euan to talk about how this could lead to new insights that could have significant translational and clinical impact.

[00:59:53] As an aside, Ken talks about what makes AI tools effective in the hands of physicians as well as the limitations of AI in physicians’ hands.

[01:01:02] Dawn pivots back to the work Euan did with Steve and his genome. Dawn mentions that Steve pointed out to Euan in that encounter a variant in one of his genes associated with heart disease, a variant that could be life-threatening. Dawn goes on to explain that accurate assessment of cardiac function is crucial for diagnosing cardiovascular disease. In one of Euan’s papers, he addressed the limitations of human assessment of cardiac function. In order to overcome this challenge, Euan and his colleagues developed a video-based deep learning algorithm, EchoNet-Dynamic, which surpasses human observation in several critical tasks related to the assessment of cardiac health. Dawn asks what went into the development of EchoNet-Dynamic and what makes it standout as an assessment of cardiac function.

[01:05:13] Ken explains that IHMC has three primary overlapping research focus areas: artificial intelligence; robotics and exoskeletons; and human healthspan, resilience and performance. He also mentions that IHMC is building a new research complex dedicated to healthspan, resilience and performance research. Dr. Marcas Bamman will be the director of the new complex and will help lead clinical and translational research to advance knowledge on optimizing the performance and resilience of elite performers. Because of this research, Ken was particularly interested in Euan’s paper in Nature last year titled “The Genetics of Human Performance.” The article points out that while we have substantial epidemiological evidence supporting the beneficial effects of exercise, we really don’t know a lot about the molecular mechanisms through which these effects operate. But we do know that exercise extends healthspan. Ken explains that the article reviewed the current understanding of the genetics of human performance, and it begins by pointing out that compared to our recent hominid ancestors, humans seem to have evolved for endurance physical activity. Ken asks Euan to talk about this and why it matters in terms of modern humans.

[01:09:05] Dawn mentions that Euan and his co-authors on the aforementioned paper reviewed the large body of research that has shown that all forms of exercise, particularly endurance exercise, confer benefits across all domains of health and function. The paper goes on to review recent research that identifies specific genetic pathways that may underline the beneficial effects of endurance exercise. Dawn asks Euan to talk about these genetic pathways and the key points of the review and its primary conclusions.

[01:11:31] Ken asks Euan about his thoughts on the significance of the role of the microbiome in enhanced endurance activity.

[01:14:23] Ken explains that while some genetic variants identified to date account for small portions of the variance in exercise training adaptations and/or human performance, it seems the major determinants of inter-individual differences may lie in dynamic expression responses which are largely influenced by the dynamic epigenome. Ken asks Euan what he thinks are the critical paths forward in exercise epigenomics.

[01:16:48] Ken explains that Euan is involved in projects via the Wu Tsai Human Performance Alliance to identify new genetic variants that have larger effect sizes on human performance than those previously identified. Ken asks Euan to talk about the importance of the ELITE project in this context.

[01:19:11] Dawn asks Euan about his book “The Genome Odyssey,” which was described by the Wall Street Journal as an impassioned, firsthand account of the effort to bring genomic data into clinical practice. Dawn asks what Euan was hoping to accomplish with the book.

[01:20:36] Dawn explains that in the Wall Street Journal review of the book, it highlights Euan’s account of the remarkable progress of genetic medicine over the past two decades, and also mentions how Euan believes more wondrous advances are on the way. Dawn asks Euan to talk about some of these advances.

[01:22:19] Dawn mentions that in Euan’s Stanford bio, it mentions that he is a father of three and that in his spare time he plays jazz saxophone, pilots small planes, and conducts research on the health benefits of single malt Scotch whisky.

[01:23:23] Ken mentions that Euan’s bio also says that he is on a quest to better understand American football and asks Euan how that’s coming.

Links:

Euan Ashley bio

Learn more about IHMC

STEM-Talk homepage

Ken Ford bio

Ken Ford Wikipedia page

Dawn Kernagis bio