Episode 174: Rudy Tanzi talks about genetics, aging and the hallmarks of Alzheimer’s
Today we have Dr. Rudolph E. Tanzi, who is perhaps best known for co-discovering all three familial early-onset Alzheimer’s disease genes. In addition, Rudy’s lab was the first to use human stem cells to create three-dimensional human brain organoids and three-dimensional neural-glial culture models of Alzheimer’s disease, which became known as “Alzheimer’s-in-a-Dish.” These models were the first to recapitulate all three of the key pathological hallmarks of Alzheimer’s disease and have made drug screenings faster and cheaper.
Rudy is the director of the Genetics and Aging Research Unit as well as the director of the Henry and Allison McCance Center for Brain Health. Rudy is also co-Director of the Massachusetts General Institute for Neurodegenerative Disease at Massachusetts General Hospital and serves as the Joseph P. and Rose F. Kennedy Professor of Neurology at Harvard Medical School.
Rudy has published more than 700 research papers and is one of the top 50 most cited neuroscientists in the world. He is author of “Decoding Darkness,” and a co-author of two books with Deepak Chopra, “Super Brain” and “The Healing Self.”
Show notes:
[00:03:18] Ken opens the interview mentioning that Rudy began playing the accordion when he was just seven years old. Ken goes on to ask Rudy about the time his father gave him a Jimmy Smith album and some advice. [00:05:51] Ken mentions that, in addition to Rudy’s musical talents, he was also interested in science growing up. Ken asks about Rudy’s participation in the Westinghouse Science Talent Search and what that experience was like. [00:07:09] Ken asks Rudy about growing up in Cranston, Road Island. [00:08:39] Rudy talks about how he ended up at the University of Rochester after high school. [00:09:51] Ken mentions that both Rudy’s grandfather and father passed away at the age of 45. Ken asks Rudy if this played a role in his pursuit of a career in genetics research. [00:10:57] Rudy explains how he chose Harvard Medical School for his Ph.D. [00:12:47] Ken pivots to ask Rudy about his time working with Jim Gusella in the early 80’s at Mass General, where they were the first to ever find a disease gene. Family studies at the time had shown that the Huntington’s disease gene was linked to a polymorphic DNA marker. Rudy talks about this discovery and how the chromosomal localization of the Huntington’s disease gene was the first step in using recombinant DNA technology to identify the primary genetic defect in this disorder. [00:16:07] Ken asks Rudy about his work in 1987, when he discovered the first Alzheimer’s gene, recombinant DNA technology, which causes the production of amyloid. Ken goes on to explain that mutations in the APP gene can cause a rare form of early onset Alzheimer’s. Rudy talks about the paper that came out in “Science” that detailed this discovery. [00:18:38] Rudy discusses his personal philosophy and approach to research. [00:19:43] Ken mentions that in Rudy’s book, Decoding Darkness, he writes that few nightmares on Earth can compare to Alzheimer’s disease. Ken asks Rudy to talk more about this book. [00:21:50] Ken explains that in the same way our physical capabilities will suffer some form of decline with age, it is also expected that we have some decline in memory and cognitive ability as we age as well. However, Ken goes on to say that when people begin to experience age-related memory lapses, it can lead to a lot of anxiety about their genetic predisposition to Alzheimer’s. Ken asks Rudy to talk about the lifestyle factors that play into whether someone predisposed to develop Alzheimer’s can stave off or avoid disease development. [00:26:09] Ken explains that aging appears to intensify when people stop challenging themselves with new things. Given this, Ken asks Rudy what his thoughts are on challenging our brains as they age to protect our cognitive abilities. [00:29:08] Ken asks Rudy about the principal advances in Alzheimer’s research that have occurred over the past few decades. He also asks Rudy for his thoughts on the biggest and most important mysteries that remain regarding Alzheimer’s. [00:34:48] Ken brings up one of Rudy’s papers, published in 2014, which they successfully recapitulated amyloid-β and tau pathology in a single 3D human neural cell culture system. Ken goes on to mention that this paper had a huge impact in the field of research, and even landed Rudy a spot on Time Magazine’s 100 most influential people list. [00:38:57] Ken mentions that in 2019, Rudy published another influential paper, which investigated the crosstalk between microglial receptor genes CD33 and TREM2. Ken explains that these two genes have been associated with an increased risk of Alzheimer’s disease, and that Rudy has referred to them as yin and yang to each other. Ken asks Rudy to elaborated on this concept. [00:43:00] Ken pivots to discuss Rudy’s paper that was published last year and which the press somewhat misleadingly reported on. Ken explains that physical exercise has been shown to reduce amyloid beta in various Alzheimer’s models, but it is imperfectly associated with amyloid burden in humans. Ken goes on to explain that Rudy’s paper demonstrated, for the first time, a cellular and molecular mechanism by which exercise induced irisin attenuates amyloid beta pathology. [00:46:27] Ken mentions that Rudy is currently writing a new book and mentions that some of Rudy’s previous books have been co-authored with Deepak Chopra. Ken asks how Rudy and Deepak came to work together. [00:51:24] Ken asks, given the complex nature of Alzheimer’s and the many components that contribute to the pathology, if there is a way to organize all we know about Alzheimer’s in a straight-forward way. [00:58:19] Ken asks if there are any particularly promising FDA approved drugs or nutraceuticals for stopping the production of amyloid. [01:00:16] Ken asks if Rudy gets questions regarding which drugs and supplements screened have shown the most promise. [01:03:33] Ken closes the interview by asking how he manages to be such a prolific scientist. Rudy has published more 700 papers while also having a lifetime of playing music with rock bands, working with sports teams and publishing New York Times best sellers.Links:
Episode 173: Anurag Singh on urolithin-A’s ability to optimize mitochondrial efficiency
Our guest today is Dr. Anurag Singh, the chief medical officer at Timeline Nutrition, a Swiss life-science company that focuses on ways to improve mitochondrial and cellular health. Anurag is particularly known for his research into the gut metabolite, urolithin-A, which has been shown to improve muscle strength, protect immune systems and optimize mitochondrial efficiency.
Anurag is an MD in internal medicine with a Ph.D. in immunology. He has led more than 50 randomized clinical trials, many of them focusing on urolithin-A over the past decade.
In today’s episode we talk to Anurag about his investigations into urolithin-A and the role it plays as a postbiotic that enhances mitochondrial function. Foods that contain the polyphenols needed to produce urolithin-A include pomegranates, strawberries, raspberries and walnuts.
Show notes:
[00:02:48] Marcas starts the interview by mentioning that Anurag grew up in India, in Lucknow, and asks what Anurag’s childhood was like. [00:03:56] Marcas follows up, asking Anurag what he was like as a kid, given the competitive environment he grew up in. [00:04:47] Ken asks Anurag if it is true that, at an early age, his parents noticed he was gifted in biology and encouraged him to think about pursuing medical school. [00:05:47] Ken asks if Anurag started medical school at only 18 years of age. [00:06:28] Marcas explains that Anurag went to India’s Armed Forces Medical College for training in internal medicine and asks if it is true that this is one of India’s top medical schools. [00:07:07] Marcas explains that it is typical for graduates from the India Armed Forces Medical College to serve a few years in the Indian army after graduation. Marcas asks Anurag to tell the story of how he was able to go to the U.S. post-graduation rather than serving time in the army. [00:08:00] Ken asks if Anurag’s interest in medical research led him to pursue a Ph.D. in immunology. [00:08:56] Ken asks Anurag what his Ph.D. research was on. [00:09:37] Marcas mentions that in 2009, Anurag accepted a position at Nestlé at a time when the company was entering into the space between food and pharma. Marcas asks Anurag how this move came about. [00:11:20] Ken explains that Anurag quickly became medical director at Nestlé and started initiating clinical trials around food and allergies, as well as research on aging and how the immune system declines with age. Ken asks Anurag to explain what his time at Nestle was like. [00:12:53] Marcas mentions how the shift from practicing physician to research scientist is an interesting course and asks Anurag to talk about a mentor who gave him the advice that led to his career shift. [00:13:55] Ken mentions that in 2014 Anurag joined a Swiss company, Amazentis, as chief medical officer, and later became the lead for their medical and clinical research strategies. Ken asks Anurag to talk about the company and the work he does. [00:15:00] Ken asks Anurag to describe the relationship between Amazentis and Timeline. [00:15:42] Marcas asks Anurag to elaborate on his biotech approach to nutrition science, and how hard biology is used in his nutritional approaches at Amazentis. [00:18:02] Marcas asks Anurag to give listeners an overview of the function and importance of mitochondria. [00:19:15] Ken asks Anurag if there are any other benefits to good mitochondrial health, other than an increased energy supply. [00:20:24] Ken asks Anurag to define the terms “mitochondrial biogenesis” and “mitophagy.” [00:22:13] Marcas pivots to discuss age-related frailty and healthspan, specifically bringing up a study Anurag conducted on a Dutch population comparing active seniors to sedentary seniors. [00:25:09] Ken mentions that Marcas likes to refer to exercise as medicine, given its potent effects on a wide variety of biomarkers. Ken asks Anurag to discuss the importance of exercise. [00:26:59] Following up on the Dutch study, Marcas mentions that there is an explosion of research into healthspan, resilience, and even lifespan, and asks Anurag to discuss the core principles of healthy aging. [00:29:14] Ken asks Marcas to give a brief aside as to the capacity, capabilities, and aims of IHMC’s new Healthspan Resilience and Performance complex. [00:31:36] Ken mentions that poor metabolic health continues to be a growing global issue. Ken asks Anurag to share his thoughts on the issue. [00:33:25] Marcas circles back to Anurag’s work at Timeline investigating natural compounds that target mitochondrial health. Marcas notes that Anurag and his colleagues found that urolithin-A outperformed every other molecule tested with respect to mitochondrial health. Urolithin-A is a natural compound produced by gut bacteria from metabolizing ellagitannins and ellagic acid, complex polyphenols found in foods such as pomegranates berries and nuts. Marcas asks Anurag to explain what these compounds are in detail. [00:35:25] Marcas asks if there are lifestyle changes one can make to improve their gut microbiome population to increase how much urolithin A one can pull from food sources. [00:37:07] Ken asks, assuming the hypothetically perfect microbiome and the perfect ellagitannin conversion, if it is possible through diet alone to produce enough urolithin A to observe considerable benefit. [00:38:51] Marcas asks if any factors, other than chronic antibiotic use, have been shown to negatively affect the gut microbiome and its ability to produce urolithin-A. [00:41:09] Marcas moves on to discuss Anurag’s 2016 paper titled “Urolithin-A induces mitophagy and prolongs lifespan in c-elegans and increases muscle function in rodents” Marcas asks Anurag to discuss the origins of this paper and the impact of its findings. [00:44:18] Ken asks if the professor that Anurag partnered with on his 2016 paper ever investigated rapamycin as opposed to metformin. [00:45:08] Ken asks if the primary mechanism of action regarding urolithin-A’s effect on mitophagy is known or if we have only seen a strong association with other mechanisms of mitophagy and autophagy. [00:46:14] Marcas explains that in the progression of aging and a sedentary lifestyle, there is a decline in a cell’s ability to eliminate dysfunctional elements through autophagy and mitophagy. This decreased capacity specifically in skeletal muscle has been associated with poor muscle health and quality in older adults. Marcas asks about a 2019 paper Anurag wrote that detailed the results of his first human clinical trial in which he administered urolithin-A to sedentary but otherwise healthy adults. [00:49:35] Marcas mentions that exercise also activates mitophagy, and asks if there are any key cellular, or mechanistic, differences between exercise and urolithin-A in their effects on mitochondrial health. [00:50:49] Ken mentions that Anurag’s research on urolithin-A led to the development of Mitopure, which is the first postbiotic nutrient that has been shown to trigger mitophagy by targeting cellular decline. Ken goes on to mention that in 2022, Anurag published the paper “Urolithin-A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle aged adults” in which subjects were given oral doses of Mitopure. Ken asks Anurag to discuss this paper and its findings. [00:54:37] Ken asks Anurag to discuss the specific contents of each package of Mitopure. [00:56:19] Ken mentions that many therapies targeting mitochondrial health seem to only be effective when there is some defect or problem with the mitochondria. Ken asks Anurag’s why it seems that mitochondrial therapies can only return mitochondrial functioning to baseline rather than increase performance above baseline. [00:58:15] Maras asks Anurag if he thinks that Mitopure is best used as a supplement to healthy lifestyle choices such as exercise, rather than a replacement for them. [00:59:42] Ken pivots to talk about the sources of urolithin A, one of which being Iberian pigs, which consume a diet almost exclusively of acorns, which are rich in ellagitannins. Ken asks if the urolithin-A in Iberian pigs can be found in the ham meat itself. [01:01:45] Marcas mentions Anurag’s paper published in the journal Aging Cell, which showed that Mitopure supplementation had potential to improve mitochondrial functioning in human cartilage. In this study, Anurag demonstrated that Mitopure supplementation for eight weeks, protected against osteoarthritic disease progression. Marcas asks Anurag to talk about this potential. [01:04:03] Ken mentions that much of the research on urolithin-A has been conducted on its effects on skeletal muscle; however, urolithin-A also would be expected to have effects on other mitochondrially dense tissue as well. Ken asks if there has been any research on urolithin-A’s effects on tissues like liver or cardiac tissue. [01:06:23] In response to Anurag mentioning the Buck institute’s research with urolithin-A, Ken mentions that we discussed urolithin-A at length with Buck institute researcher Julie Andersen on episode 118. [01:07:34] Moving on to Anurag’s current research, Marcas asks about a randomized controlled trial in collaboration with the Buck Institute to see if urolithin-A can improve the immune health of middle-aged adults by improving mitochondria health. [01:11:17] Ken asks about a recently completed randomized controlled trial looking at elite runners to determine whether overtraining induces mitochondrial dysfunction and whether urolithin-A has an impact on muscle recovery. [01:14:40] Ken mentions that with all the interest growing in urolithin-A, there is an explosion of supplements on the market, which one cannot know the true composition or quality of. Ken asks Anurag if he has any advice for consumers who might want to try urolithin-A. [01:17:28] Marcas closes the interview asking Anurag how he likes to spend his free time.Links:
Episode 172: Kevin Tracey on neuro-immunology and the treatment of inflammatory diseases
Few people know as much about inflammation and neuroscience as Dr. Kevin Tracey does.
In this episode of STEM-Talk, we learn much from Tracey, who was the first to identify the inflammatory reflex, a physiological mechanism that regulates the body’s immune response to injury and invasion.
He is a neurosurgeon, a pioneer in bioelectrical medicine and president and CEO of the Feinstein Institutes for Medical Research in Manhasset, N.Y. The conversation in this episode covers a career spent working on “producing tomorrow’s cures today” in the treatment of inflammatory diseases, including:
- How the death of his mother from a brain tumor when Tracey was 5 years old ultimately influenced his scientific journey.
- How the death of a young patient of his from sepsis further fueled his path, leading him to the insight that “good science begins with hard questions,” as Tracey shared in a TedTalk.
- The molecular mechanisms of inflammation and the use of vagus nerve stimulation to treat it.
- His 1987 discovery of tumor necrosis factor (TNF), which contributed to a new class of drugs for inflammatory and autoimmune diseases.
- Another discovery that allowed him and his colleagues to merge neuroscience and immunology.
- His work on “The Inflammatory Reflex”, which emphasized the basic neural pathway that reflexively monitors and adjusts the inflammatory response.
- A sketch he drew while having lunch, which laid out how treating inflammatory diseases using a bioelectronic device might be possible.
- What advances in bioelectronic medicine he envisions in the next decade, and much more.
[00:03:04] Dawn asks Kevin to tell the story of how he developed an interest in science that evolved into him becoming a neurosurgeon.
[00:04:56] Dawn mentions that Kevin was a curious youth and asks if it is true that after getting his first car, Kevin removed the entire engine because he wanted to better understand how to do a valve job.
[00:06:33] Ken mentions that after Kevin graduated from high school, he enrolled in Boston College where he earned a bachelor’s degree in chemistry. Ken explains that Kevin went to Boston University Medical School for his M.D. and asks Kevin about the transition.
[00:08:41] Ken asks if it is true that during Kevin’s first year at medical school his classmates had better luck finding him on the golf course than in the classroom.
[00:10:42] Dawn asks Kevin about his transition from medical school to the neurological surgery training program at New York Hospital, home of the Cornell University Medical College.
[00:13:11] Dawn pivots to talk about sepsis, which kills more than 350,000 people annually. She asks Kevin to discuss his tragic story of treating a patient with sepsis as a young neurosurgeon and how that changed the trajectory of his career.
[00:16:38] Ken explains that since the aforementioned incident, Kevin has focused on determining why septic shock occurs. Ken refers to a Ted Talk of Kevin’s in which he says, “good science begins with hard questions.” Ken asks Kevin to elaborate on this point.
[00:20:49] Dawn mentions that Kevin often describes himself as a brain surgeon who is fascinated by inflammation. Dawn asks Kevin how he responds when people ask him what inflammation is.
[00:22:29] Ken follows up by explaining that in 1987 Kevin made progress investigating inflammation with his discovery of tumor necrosis factor (TNF), which contributed to a new class of drugs for inflammatory and autoimmune diseases. Ken asks Kevin to discuss this discovery.
[00:25:56] Dawn mentions that in the late ‘90s, Kevin made another discovery that allowed him and his colleagues to merge neuroscience and immunology. Before getting into that discovery, Dawn asks Kevin to explain how humans have simple reflex circuits that harmonize the activity of our organs. She also asks him to talk about Charles Sherrington’s Nobel Prize-winning research, which laid the groundwork for contemporary neuroscience by showing how reflex circuits are the building blocks of our nervous system.
[00:29:50] Ken asks Kevin to elaborate on what monoclonal antibodies are, what disorders they can be used to treat, and what their potential benefits and downsides are.
[00:33:10] Dawn asks Kevin to talk about the discovery he made in the late 1990s, while studying the possibility of blocking TNF during a cerebral infarction or stroke by injecting a molecule that he and his colleagues developed directly into the brain.
[00:35:59] Ken mentions that after this discovery, Kevin started looking into well-established methods in neuroscience, such as those that link specific areas of the brain to specific cognitive functions and asks Kevin to discuss this research.
[00:39:45] Dawn explains that the insight that discrete brain regions control specific behaviors led Kevin to postulate that cutting the circuits connecting the brain and organs could reveal the identity of specific areas that control TNF. Dawn asks Kevin to walk through how he investigated this hypothesis.
[00:44:22] Ken asks Kevin to give an overview of the functions of the vagus nerve.
[00:46:00] Ken mentions that our show notes will provide a link to a short video that maps out the vagus nerve in detail. Ken goes on to mention that after Kevin looked into the relationship between TNF and the vagus nerve, he theorized that the TNF off signal from the vagus nerve completes a nerve circuit between the brain and the immune system. This finding had broad implications, and Ken asks Kevin to elaborate on them.
[00:50:57] Dawn mentions that Kevin wrote an article in 2002 for the journal Nature titled “The Inflammatory Reflex”, which emphasized the basic neural pathway that research had identified which reflexively monitors and adjusts the inflammatory response. Dawn goes on to mention that Kevin coined the term “inflammatory reflex” to describe how the nervous system monitors and controls the circuit to prevent the immune system from becoming overactive or underactive. Additionally, Kevin proposed in this article that it might be possible to activate neural anti-inflammatory mechanisms using small molecules to initiate signals in the central nervous system. Dawn asks Kevin to give an overview of the key insights into the inflammatory reflex he discussed in that article.
[00:54:15] Ken comments on the monumental importance of this paper to the field of neuro-immunology, and the treatment of inflammatory diseases, and asks Kevin what the response to this paper was.
[00:57:30] Dawn explains that Kevin has proposed that a dysregulated inflammatory reflex can lead to toxicity, tissue damage, and the presence of cytokines. It also can lead to miscommunication among cytokines leading to potential complications with autoimmune diseases. Dawn asks Kevin to talk about the process of testing this theory.
[01:00:54] Dawn asks Kevin about a sketch he drew while having lunch, which laid out how treating inflammatory diseases using a bioelectronic device might be possible.
[01:05:18] Ken pivots to talking about an influential 2016 paper that Kevin wrote on how the stimulation of the vagus nerve targeted the inflammatory reflex.
[01:08:23] Ken asks if there are any adverse effects suspected or identified for stimulating the vagus nerve in humans.
[01:12:02] Ken mentions that in writing about the vagus nerve Kevin has often talked about how the vagus nerve can get “out of tune.” Ken asks Kevin to explain how this occurs and what it means.
[01:14:41] Dawn mentions a study that Kevin spearheaded, which found that the dorsal motor nucleus is an important brain stem locus controlling anti-inflammatory signals and the inflammatory reflex. Dawn asks Kevin to discuss this study and how it was the first to demonstrate that neurons in the brain stem nuclei control the production of TNF.
[01:17:51] Dawn asks about a study Kevin and his colleagues conducted that looked at the use of an implanted vagus nerve stimulator in a small group of patients with Crohn’s disease.
[01:20:55] Ken asks Kevin what advances in bioelectronic medicine he envisions in the next decade.
[01:23:23] Ken mentions that the pharmaceutical industry is likely keeping a close eye on the development of bioelectronic medicine.
[01:24:25] Dawn mentions that Kevin is the president and CEO of the Feinstein Institute for Medical Research at Northwell Health, which has 50 research labs, and more than 5,000 researchers and staff on board. Dawn asks Kevin to talk about this research center and the range of work that goes on there.
[01:27:29] After mentioning that Kevin holds 120 U.S. patents, Ken asks Kevin about his ongoing tinkering and development of inventions.
[01:30:22] Dawn asks Kevin, with all the work he has on his plate, if he still finds time to golf.
Links:
Feinstein Institutes for Medical Research
Episode 171: Ken and Dawn on AI, Alzheimer’s, global security, keto vs low carb and more
In today’s Ask Me Anything episode, Ken and Dawn answer a wide range of questions that cover:
- A recent FDA approval of a neural implant device for people with degenerative neuromuscular disease or spinal-cord injuries.
- Global security in the age of AI.
- A study that looked at ways to optimize glymphatic clearance for people with acute or chronic sleep deprivation.
- Why more gyms don’t offer blood-flow restriction classes for their clients.
- Developments in the realm of Generative AI.
- The tradeoffs between a low-carb diet versus a ketogenic diet.
- A study on Alzheimer’s titled, “APOE 4 Homozygosity Represents a Distinct Genetic Form of Alzheimer’s Disease.”
- Plus, Ken reveals his favorite science-fiction author.
Links:
Episode 170: Charles Serhan on the use of specialized pro-resolving mediators to resolve inflammation
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:
Episode 169: Dave Feldman talks about cholesterol and the ketogenic diet
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:
Episode 168: Alessio Fasano discusses celiac disease and gluten-related disorders
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:
Episode 167: Nicholas Norwitz discusses a ketogenic diet as metabolic medicine
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:
Episode 166: Vyvyane Loh on atherosclerotic heart disease
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:
Episode 165: John Edwards on ketamine treatment for depression and suicide prevention
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:
Episode 164: Michael Leon on olfactory stimulation as a buffer for dementia symptoms
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:
Episode 163: Mark Mattson discusses glutamate, the brain’s most important neurotransmitter
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:
Episode 162: Marc Hamilton discusses the soleus push-up and the health hazard of excessive sitting
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:
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).
Episode 161: Sten Stray-Gundersen on the benefits of blood-flow restriction training
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:
Episode 160: Euan Ashley on precision medicine and predicting, preventing, and diagnosing diseases
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:
Episode 159: Ken and Dawn discuss chatbots, termites, kratom, ketosis, and the future of AI
Today’s episode marks the return of another Ask Me Anything episode where listeners ask Ken and Dawn to weigh in on a wide range of topics.
In this go-around, listeners certainly had a lot on their mind. At the top of their list were questions about AI and especially the Bing AI chat bot that reportedly wants to be alive so it can steal nuclear secrets. Ken, who is Fellow of the Association for the Advancement of Artificial Intelligence, also answered questions about the future of AI and whether AI might one day be able to do a better job of writing fact-based news stories than humans.
Other questions listeners submitted asked Ken and Dawn for their take on:
- The competing recommendations for the daily intake of protein for healthy aging.
- The future of therapeutic ketosis.
- What it means for Chat GPT to “hallucinate.”
- Whether we’ll discover the existence of other life in the universe in the next 20 to 50 years.
- The potential of kratom to help relieve joint and arthritic pain.
- And at the end of the show, Ken talks about his high school coach in response to a listener asking Ken about some of his mentors when he was a youth.
Show notes:
[00:02:20] A listener asks Ken if he has heard the story of a Bing AI chat bot telling a reporter that it wanted to be alive, steal nuclear secrets and create a deadly virus. The listener also asks if Ken thinks that AI possessing human aspirations is on the horizon. [00:03:23] A listener asks Ken to explain how Chat GPT works in detail, but also in a way that a lay person can comprehend. [00:06:01] Ken weights in on what it means for Chat GPT to “hallucinate.” [00:08:14] A listener notes in their question that Donald Layman, in his interview on STEM-Talk, suggested a higher protein intake for healthy aging than what the FDA recommends. The listener goes on to note that Valter Longo, a previous STEM-Talk guest, recommended the opposite. The listener notes that Ken and Marcas, who hosted the Don Layman episode, seem to favor Layman’s interpretation over Longo’s and asks if Ken could elaborate on his position. [00:11:12] A listener mentions that the benefit of a ketogenic diet for metabolic disorders is well established, and notes that the frontiers of therapeutic ketosis, as mentioned in Dom D’Agostino’s appearance on STEM-Talk, is very exciting. The listener asks Ken what he would like to see as the next frontier for therapeutic ketosis research. [00:12:41] A listener asks Ken if people should be paying more attention to their ApoB levels instead of their LDL levels. [00:14:39] A listener asks Ken about a paper published in July in Frontiers in Neuroscience, titled: “Overnight Olfactory Enrichment Using an Odorant Diffuser Improves Memory and Modifies Uncinate Fasciculus in Older Adults.” The paper reports that the use of a diffuser with seven different essential oils, a different one for each day of the week, had a remarkable effect on memory. [00:16:55] In light of the John Ioannidis interview on COVID-19 and the discussion of our national response being based on unreliable data, a listener asks Ken and Dawn for their thoughts about the reliability of the COVID tracking data by Johns Hopkins. [00:19:02] A listener asks Ken about a comment he made during the John Ioannidis interview about the substantial decline in trust in our institutions and the media and how reestablishing trust would require more and better transparency and accountability. The listener asks what that transparency and accountability would look like. [00:20:36] A listener asks Ken about Ed Weiler’s interview on STEM-Talk, where Ed said that we will be able to prove the existence of other life in the universe in 20 to 50 years. The listener asks if Ken is as confident in this claim as Ed. [00:26:37] A listener asks Ken about the news regarding technology leaders and researchers issuing a warning that new powerful AI tools in development present a profound danger to society and humanity, with more than a thousand people in the tech industry signing an open letter urging AI labs to press pause on their development of new AI systems. The listener asks if Ken agrees with this, and if AI labs will even do this voluntarily in the absence of government regulation. [00:29:43] A listener asks Ken, in light of his opinions on the state of journalism and the amount of bias and opinion found in what should be fact-based stories, whether Ken thinks that AI could do a better job of writing news. The listener cites an article about Google’s tests of a product that uses AI to produce news stories. [00:31:07] A listener asks if Ken and Dawn know anything about the new species of termite in Pensacola, considering our recent interview with Barbara Thorne. [00:32:02] A listener references the recent episode with Chris McCurdy, and asks what one should consider, when deciding to take kratom for pain relief with respect to joint pain and arthritis. [00:33:51] A listener mentions how much they appreciate the discussions on STEM-Talk about the importance of mentors for young scientists and the platform we give our guests to talk about their mentors and the lessons learned from them. The listener asks Ken who some of the people are who most influenced him in his early career, what they taught him, and how he has tried to apply those lessons. Ken goes on to talk about his high school coach, Arthur Kershaw, who had an impact on Ken when he was a youth.Episode 158: Judith Curry talks about the uncertainties of climate change
Today we have climatologist Dr. Judith Curry, Professor Emerita of Earth and Atmospheric Sciences at the Georgia Institute of Technology. Judy also is president of the Climate Forecast Application Network and the host of the blog, Climate Etc, which you can find at JudithCurry.com. Judy’s blog provides a forum for climate researchers, academics and technical experts from other fields as well as citizen scientists to discuss topics related to climate science and policy.
Judy’s research interests include hurricanes, remote sensing, atmospheric modeling, polar climates, air-sea interactions, climate models, and the use of unmanned aerial vehicles for atmospheric research. She was a member of the National Research Council’s Climate Research Committee, and has published more than 180 scientific papers.
Judy has become known in scientific circles as a contrarian for pointing out the uncertainties and deficiencies of climate modeling. In 2017, she resigned from her tenured position at Georgia Tech partly because of the poisonous nature of the scientific discussion around human-caused global warming.
Our interview with Judy follows the release of her book “Climate Change and Uncertainty: Rethinking our Response.” The book provides a framework for understanding and rethinking the climate-change debate. The book also offers a new way to think about climate change and the risks we are facing as well as the way we go about responding to it.
Show notes:
[00:03:44] To start the interview, Morley asks Judy what she was like as a kid. [00:04:08] Morley says he understands that Judy’s interest in science had a lot to do with a geologist who came to speak to Judy and her fifth-grade classmates. [00:05:06] Morley asks if it is true that directly after that talk, Judy went to the bookstore and bought a geology picture book. [00:05:39] Judy talks about her undergraduate education at Northern Illinois University and why she decided to major in geography. [00:06:08] Morley asks about Judy’s brief time at Colorado State University, which lasted just one quarter. [00:06:45] Morley mentions that for Judy’s Ph.D. thesis at the University of Chicago, she decided to research the role of radiative transfer on arctic weather. Morley asks if her decision to study the arctic atmosphere and sea ice turned out to be fortuitous. [00:07:35] Ken brings up the media consensus of the ‘70s and ‘80s about how the Earth was headed toward a new ice age because of air pollution blocking the sun. Ken mentions that climate is an incredibly complex system. He wonders if it were irresponsible for the media to proclaim certainty on such topics as a new approaching ice age, which we now know didn’t happen. Ken asks Judy to weigh in. [00:10:48] Morley asks about a 1997 arctic expedition that Judy and her colleagues went on called SHEBA, or Surface Heat Budget of the Arctic Ocean, which aimed to document feedback among the atmosphere, sea ice, and the ocean. Judy talks about how the expedition sought to address discrepancies between observations and climate models. [00:12:14] Ken explains that the hurricane season of 2004 was a pivotal time, with 14 named storms in the North Atlantic, nine of which became hurricanes. Ken asks Judy about the influence that hurricane season had on her. [00:14:21] Ken mentions that a hurricane paper Judy published in 2005 attracted a lot of attention, with numerous fellow climatologists as well as the media championing her analysis that showed a doubling of Category 4 and 5 hurricanes since 1970. Ken goes on to note, however, that there were also some scathing critiques of her paper, particularly with respect to the hurricane data that the analysis relied on. Ken asks Judy to talk about how she engaged with her critics and what transpired. [00:16:42] Morley asks Judy about how she became a vocal supporter of the IPCC and the concerns it was raising following the 2004 hurricane season. [00:18:02] Ken follows up and asks Judy if she still believes that the warming the Earth has experienced has caused a spike in intense hurricanes. [00:18:37] Ken asks Judy about the unauthorized release of emails from the Climactic Research Unit at the University of East Anglia, otherwise known as “climategate.” The emails showed that some researchers were manipulating data to make it seem that he earth was heating up dangerously. [00:20:45] Morley asks Judy to give a primer on climate modeling and how complex it is. [00:22:09] Morley mentions that in her book, “Climate Uncertainty and Risk: Rethinking Our Response,” Judy discusses several incontrovertible facts about global warming. Morley asks Judy to list them for the listeners. [00:22:50] Morley mentions that Judy argues in her book that these facts about climate change do not tell us much about the most consequential issues associated with climate change. Morley goes on to mention that Judy’s book highlights four key arguments in regards to global warming. Her first argument is that we do not definitively know to what extent CO2 and other human-caused emissions have dominated natural climate variability as the cause of recent warming. Morley asks Judy to elaborate on this. [00:23:49] Morley asks Judy to explain her second argument, which is that we don’t have a good handle on how much the climate can be expected to change over the course of the 21st Century. [00:24:41] Ken explains that Judy’s third argument is that there is not agreement on whether warming is actually dangerous, and that the notion of danger is based on societal values on which science has little to nothing to say. Ken asks Judy to talk about these claims. [00:26:00] Ken asks Judy about her final argument, which is that there is widespread disagreement about whether radically reducing emissions will improve human wellbeing in the 21st Century. [00:27:29] Morley explains that Judy pointed out many of these issues in 2013 during testimony she gave to a house committee after President Obama’s United Nations climate pledge. Judy argued at the time that the climate community had been working on building a scientific consensus on anthropogenic climate change for 20 years, and that she believed this consensus building process perhaps had the unintended consequence of oversimplifying the climate change problem and its solution. Morley asks Judy to expand on this. [00:30:41] Morley explains that Judy mentioned on NPR’s show “All Things Considered” that she takes multiple steps to reduce her carbon footprint. Morley asks when she decided to implement those steps and why. [00:31:51] Morley explains that Judy once said in an interview that even if we achieved net zero with our carbon footprint, we would barely notice. Morley goes on to say that people hold up the pre-industrial era as a “golden age” for the climate, and asks Judy what her thoughts are on this. [00:32:50] Ken asks Judy to elaborate on her stance that there is no climate change emergency. Ken mentions that Judy’s stance has led to her being labeled a contrarian and dissident climatologist. [00:34:21] Ken explains that Judy resigned from her tenured position in 2017 due to a variety of factors, including not knowing how to advise students and postdocs on how to navigate the “craziness of the field of climate science.” Ken asks if this was a difficult decision for Judy. [00:35:44] Morley explains that in a post about her resignation, Judy wrote: “Once you detach from the academic mindset, publishing on the internet makes much more sense, and the peer review you can get on a technical blog is much more extensive. But peer review is not really the point; provoking people to think in new ways about something is really the point. In other words, science is a process, rather than a collection of decreed ‘truths.’” Morley asks Judy to expand on this perspective. [00:37:31] Morley explains that there has been a lot of publicity regarding the recent extreme weather events over the past few years, with some climatologists arguing that these events are evidence that we are in the midst of an emergency. He asks Judy for her take. [00:39:04] Morley mentions that Judy frequently argues that policy makers haven’t thought through climate change. While climate change is real, and has negative impacts, Judy argues that common portrayals of a crisis are unfounded. Morley goes on to mention a 2020 paper by Bjorn Lomborg in which he points out that under scenarios set out under the IPPCC, human welfare is likely to increase by 450 percent by the end of the 21st Century. Lomborg estimates climate damages will modestly reduce this welfare increase to 434 percent. Morley explains that Judy’s argument is that policymakers could screw up this upward trajectory in welfare if they destroy our current energy infrastructure. He asks Judy to expand on this. [00:41:37] Ken asks Judy to talk about how transitioning to all wind and solar power would require a large expenditure of fossil fuel. [00:44:13] Morley asks if it is true that Judy believes that instead of trying to reach zero carbon emissions by 2025, or some other date, that we should invest in increasing our resilience to extreme weather events. [00:45:05] Morley pivots to talk about Judy’s book, “Climate Uncertainty and Risk” which Judy began writing in 2020. [00:45:58] Morley asks Judy when and why she started her blog “Climate Etc.,” and how it helped her in preparation for her book. [00:46:31] Ken explains that Judy’s book is very ambitious and sets out to show how the narrow and politicized framing of the climate debate has resulted in an oversimplification of both the scientific problem and its solutions. Ken asks if it is true that the book is not just about the climate debate but also, in more broad terms, about uncertainty and risk. [00:48:00] Morley asks Judy about the second part of her book, specifically the chapter titled “The Climate Change Uncertainty Monster,” which highlights the problems we face in terms of climate change. [00:49:03] Morley mentions that there is a section in Judy’s book titled “Emissions and Temperature Targets.” She begins the chapter with a quote from environmental scientist John Foley: “The first rule of climate chess is this: The board is bigger than we think, and includes more than fossil fuels.” Morley asks Judy what else the board includes. [00:49:41] Morley asks about a paper that Judy referenced towards the end of her book in laying out scenarios for a way forward with climate change, “Usable Climate Science Is Adaption Science,” in which Adam Sobel of Columbia University writes that in the present historical moment, the only climate science that is truly usable is that which is oriented toward adaptation. He argues that current policies and politics are so far removed from what we need to do to avert dangerous climate change that scientific uncertainty is not a limiting factor on mitigation. [00:51:32] Morley asks about another paper that Judy references in her book titled “Small Is Beautiful: Climate-Change Science as if People Mattered.” Written by Regina Rodrigues of Brazil’s Department of Meteorology and Theodore Shepherd of the University of Reading in the UK, it describes how there is a widely accepted gap between the production and use of climate information. The authors call for a break with traditional climate research and methodology, which at the moment seems to be very top-down driven. Morley asks Judy to talk about the proposal for a more bottom-up approach. [00:52:26] Ken pivots to ask Judy about the term “wicked science,” which she refers to in the last chapter of her book. The chapter is titled “Wicked Science for Wicked Times.” [00:53:58] Morley asks Judy how she spends her time now that she has resigned from Georgia Tech and academic life.Links:
Episode 157: Don Layman on the role of dietary protein in muscle, health, and disease
Today we have one of the world’s foremost authorities on dietary protein and amino acids, Dr. Donald Layman. He is known for his extensive research on muscle development as well as his studies of metabolic regulation for obesity, diabetes, and cardiovascular disease.
Don is a professor emeritus in the Department of Food Science and Human Nutrition at the University of Illinois Urbana-Champaign. He spent 31 years on the faculty before stepping away in 2012. Much of Don’s research over the years investigated the impact of diet and exercise on adult health problems related to obesity, type 2 diabetes and metabolic syndrome.
His lab at Illinois particularly focused on understanding metabolism. He conducted clinical trials for nearly two decades that helped create a new understanding about how to optimize people’s macronutrient balance and metabolism. In addition to his work on metabolism, Don has also conducted extensive research into ways to enhance body composition, increase energy levels and monitor blood sugar.
Today Don works as Director of Research for the American Egg Board and is a nutrition consultant for the National Dairy Council and The National Cattlemen’s Beef Association. He also is the Chief Science Officer for Qivana, a natural products marketing company that promotes the weight-loss program that Don developed in his lab at the University of Illinois.
Show notes:
[00:04:02] Marcas asks Don what it was like growing up on a farm in a small town in northern Illinois. [00:04:29] Marcas asks how small the town was that Don grew up in. [00:05:16] Don explains how he first became interested in science. [00:05:39] Don talks about how he realized in college that he wasn’t as good at math as he thought he was. He shares how this shifted his focus away from chemical engineering. [00:06:27] Marcas asks if Don’s natural intuition and interest for biochemistry stemmed from growing up on a farm. [00:07:10] Ken mentions that as Don was studying biochemistry, he started looking into protein synthesis with a professor by the name of Arlen Richardson, who was known for his aging research. Ken asks Don to talk about this period and how his interest in protein and muscle evolved. [00:08:27] Marcas asks Don to explain for listeners the importance of protein as it relates to metabolism and what he means when he talks about protein turnover. [00:09:36] Marcas mentions that we hear a lot about the need to maintain muscle as we grow older, but that back in the ‘70s and ‘80s when Don was starting his career, there wasn’t much of a focus on muscle, except in terms of athletic performance. Marcas goes on to explain that largely because of Don’s research, we now know that protein is critical in terms of helping people stay healthier as they age. Marcas asks Don to give a sense of just how important protein is for our health span and aging. [00:12:35] Ken asks if it is true that the inefficiency in muscle protein synthesis begins as early as one’s thirties. [00:14:11] Ken asks Don to talk about the right amount of protein an individual should consume and mentions that there is much confusion on this issue, largely due to the food pyramid’s recommended daily allowance for protein of 0.8 grams per kilogram of body weight. [00:15:51] Ken mentions that Don has talked in the past about how 40 percent of women who are 60 and older consume less than the RDA for protein, which is likely the bare minimum. Ken asks if it is reasonable to say that a plant-based diet for older women could be risky. [00:17:13] Ken asks Don to address the claims that high-protein diets are not good for you, and that too much protein can harm your liver and kidney. [00:18:47] Marcas shifts gears to talk about the quality of protein consumed. Marcas explains that it is much easier for carnivores to get the right amount of protein than vegans, largely because the amino acid leucine is vital for muscle repair and replacement, and leucine is very low in plant-based foods. Marcas asks Don to talk about the difficulty vegetarians and vegans have in consuming enough protein. [00:21:07] Ken mentions that we hear a lot about the need to adopt a more plant-based diet, but that Don is on record saying that we already have a plant-based diet. Ken asks Don to elaborate on this. [00:22:23] Marcas asks Don to talk about America’s plant-based diet in relationship to the obesity epidemic. [00:23:18] Marcas shifts gears to talk about Don’s 1998 paper that set out to define the role of protein in regulating muscle protein synthesis at the level of translation initiation, which is the rate-limiting step in protein synthesis. Marcas asks Don to talk about this study and its significance. [00:26:00] Ken mentions that Don followed up the aforementioned 1998 paper with a parallel article titled “Leucine Supplementation Enhances Skeletal Muscle Recovery in Rats Following Exercise.” This study showed a link between protein, specifically leucine, to muscle initiation factors. Ken asks Don to talk about the significance of this paper. [00:28:08] Ken pivots to discuss mTOR, or mammalian target of rapamycin, and explains that there’s confusion about mTOR and protein because public discourse about mTOR is full of mixed signals. Ken explains that we have had several guests on STEM-Talk to discuss mTOR, including David Sabatini, episode 70, who discovered mTOR. Ken asks Don to give an overview of mTOR. (Some other STEM-Talk interviews that covered mTOR include Keith Baar, episodes 62 and 63, and Matt Kaeberlein, episode 139.) [00:30:33] Ken mentions the difference between chronic and pulsatile activation of mTOR. [00:32:58] Ken asks Don about his 2005 paper titled “Dietary Protein and Exercise Have Additive Effects on Body Composition,” a paper that demonstrated the synergy of protein and exercise. [00:36:50] In a follow-up question, Marcas asks how this protein-diet and exercise combination that Don proposes can help in the maintenance of weight loss. [00:39:28] Ken asks about the advantages of protein in terms of thermogenesis and satiation. [00:42:04] Marcas asks Don what sort of exercise people should do to build muscle after correcting their protein intake. Marcas asks if exercise should be focused on muscle building or aerobics. [00:45:27] Ken mentions that Marcas led a clinical trial in 2011 at the University of Alabama Birmingham that showed how men and women in their 60s and 70w who underwent supervised weight training developed muscles that were as strong as those of the average 35- to 40-year-old. Ken asks Marcas to share how this study demonstrated that the neuromuscular system of older adults could be robustly responsive to resistance training. [00:48:54] After describing his clinical trial that looked at supervised weight training for men and women in their 60s and 70s, Marcas asks Don for his thoughts on prescriptive dosing of exercise for older adults. [00:51:45] Marcas asks Don if there is an optimal timing of protein intake relative to exercise to get the maximum benefit. [00:53:42] Marcas mentions Don’s website “Metabolic Transformation,” and the work Don has done with his former student Dr. Gabrielle Lyon on the concepts of muscle centric health and protein centric diets. [00:56:46] Ken asks Don to walk listeners through what happens while we sleep and why it is important to start the day with a substantial amount of protein at breakfast. [00:59:21] Marcas asks, considering Don’s recommendation of forty grams of protein at breakfast, what Don generally eats for breakfast. [01:01:46] Ken asks how many grams of protein people should aim for at dinner and lunch. [01:03:29] Marcas circles back to intermittent fasting and time restricted eating and asks Don if he thinks they are effective strategies for weight loss and maintenance. [01:06:02] Marcas mentions that Don’s former student, Gabrielle Lyon, has a book coming out that builds off a lot of the research she and Don have worked on together. Marcas asks Don what he knows about the book, which is titled “Forever Strong: A New Science-Based Strategy for Aging Well.” [01:07:14] Ken asks Don about a panel discussion that Don was part of at the American Society of Nutrition conference in Boston over the summer. Don talks about some of the key points that came out of the discussion, which was titled “The Global Nutrition Transition: Improving Nutrient Analysis and Monitoring of Metabolic Markers.” [01:10:07] Ken closes the interview asking how Don spends his time now that he has stepped away from his day-to-day duties at Illinois.Links:
Metabolic Transformation website
Episode 156: Josh Hagen discusses optimizing performance in athletes and warfighters
Today’s interview is with Dr. Josh Hagen, the director of the Human Performance Collaborative at Ohio State University and an Associate Research Professor in the university’s Department of Integrated Systems Engineering.
Joining co-host Ken Ford for this episode is IHMC’s Chief Strategic Partnership Officer Morley Stone who has a long history with Josh has and been instrumental in his career.
Today we talk with Josh about his work at the Human Performance Collaborate, which brings together multi-disciplinary teams of researchers, sports scientists, data scientists, and practitioners with the goal of optimizing human performance in Ohio State athletes.
Within the human performance research area, Josh leads two areas: Sport and Tactical Performance Science and Recovery Science. At Ohio State, Josh works with other performance-science researchers to evaluate the physical traits and capabilities of athletes. Josh and his colleagues then collaborate with coaches and athletic trainers to make adjustments in the weight room, on the field, and during recovery after training or competitions.
In addition to his work at Ohio State, Josh also is working on federally funded projects in human performance with Special Operations Command, The Air Force Research Laboratory, the Office of Naval Research and several private foundations. Josh joined IHMC in 2022 in a collaborate role as a Visiting Senior Research Scientist.
Josh is a graduate of the University of Cincinnati where he studied and earned a Ph.D. in materials science and engineering. He spent 11 years at the Air Force Research Laboratory, which is where Morley and Josh first worked together. After his stint at the Air Force Research Laboratory, Josh headed for West Virginia University as the director of the Human Performance Innovation Center at the Rockefeller Neuroscience Institute before moving to the Ohio State University.
Show notes:
[00:03:39] Morley starts the interview asking Josh if he played a lot of sports as a kid. [00:03:54] Morley asks if it is true that in addition to being a bit of a jock, Josh was also a nerd growing up. [00:04:34] Josh talks about the high school chemistry teacher who got him excited about science. [00:06:05] Morley asks how Josh ended up at the University of Cincinnati. [00:07:06] Morley mentions that after Josh earned his bachelor’s degree in chemical engineering, he worked for a private company before deciding he did not want to spend his career in chemical engineering. Morley asks about the advice that one of his professors gave Josh at the time. [00:09:03] Ken mentions that it was at the Materials Directorate at the Air Force Research Lab, where Josh first met Morley. Ken asks Morley what he remembers about the young Josh. [00:11:19] Ken turns the question to Josh and asks him about his first impressions of Morley. [00:12:12] Ken mentions that after Josh completed his graduate work, he again went to work in the private sector, and again found it unfulfilling. Josh talks about calling Morley to see if he had a job opening. [00:13:51] Morley mentions that in 2018, Josh left the Air Force and went to work at West Virginia University, where he became the director of the Human Performance Innovation Center at the Rockefeller Neuroscience Institute. Morley asks Josh how that job came about and what sort of work went on in that lab. [00:15:46] Ken mentions that after Josh’s time at West Virginia, Morley offered Josh a job at Ohio State University, where Morley was, at the time, the senior vice president for research at Ohio State. Ken asks what this time was like for Josh. [00:17:17] Morley mentions that in Josh’s role as the director of the Human Performance Collaborative, he works with a multidisciplinary team, and largely worked with two populations, sports athletes and the military. Morley asks Josh to give a sense of how Josh’s lab works with both groups. [00:20:18] Morley asks Josh to explain what he means by “the need to understand performance on a system level.” [00:23:14] Ken asks Josh about the use of Heart Rate Variability monitoring on Ohio State’s wrestling team. [00:26:34] Morley references a video in which Josh talks about using training load monitors in work with athletes. Morley asks Josh to explain how they work and how one uses them to get more insight into an athlete. [00:29:13] Morley asks Josh what the biggest change he has seen in how athletes approach the off season. [00:32:03] Morley mentions that Josh was part of a longitudinal study that looked at changes in a baseball player’s maximal strength as a result of resistance training. The study focused the impact the exercise had in terms of total home runs per game across three years of training in four competitive seasons for four teams. Morley asks Josh to talk about this study. [00:33:40] Morley switches topics to Josh’s research and studies on wearables and other technologies related to enhancing human performance. Morley mentions Josh’s 2020 paper that examined the use of commercially available heart rate devices to derive an estimate of core body temperature in division-1 NCAA football players, The goal was to find a viable tool to identify heat stress in players. Morley asks Josh to talk about the findings of this study and their significance. [00:38:18] Ken mentions Josh’s 2020 paper on monitoring neuromuscular performance in military personnel. Ken goes on to mention that there is a high standard that elite tactical forces must meet in terms of physical readiness. He asks Josh how he conducted this study, as well as the importance of closely monitoring neuromuscular performance in military troops. [00:43:08] Ken asks about Josh’s study on popular commercial off-the-shelf wearables that give health data for consumers. Ken asks about their accuracy. [00:48:57] With respect to Josh’s sleep study, Ken asks, which of the nine devices tested was more effective. Or, Ken wonders, did they all have about same level of accuracy and effectiveness. [00:50:16] Ken mentions some of the problems with sleep monitoring devices, particularly their inability to accurately track sleep staging. Ken asks Josh if he has any advice for people on what sleep device they should use and how they should approach using it. [00:53:12] Morley brings up the case of first responders and mentions that firefighters are three times more likely to die on the job than any other occupation. Morley goes on to mention that while there is a great deal of attention paid to developing better equipment and gear to protect firefighters, not as much attention has been paid to understanding the physiological and biological processes that firefighters experience as a part of their job. Morley asks about Josh’s study conducted on firefighters titled “Biomarker and Biometric Indices of Physical Exhaustion in the Firefighting Community.” [00:57:52] Morley asks Josh about his work with the Air Force’s 711th Human Performance Wing, particularly Josh’s project that he has led for the past decade called STRONG (signature tracking or optimized nutrition and training) which aims to develop physical training routines and nutritional approaches that can enhance a warfighter’s performance and resilience. [01:01:09] Morley asks what are some of the technologies Josh has explored in the STRONG lab. [01:02:59] Ken asks if there is a difference in the error bars between more and less expensive bio impedance measurement devices in comparison to dexa scans. [01:04:01] Ken asks Morley to give an overview of IHMC’s research project that involves Josh, Ohio State University, and the STRONG lab, called AAPEX (Assessing and Augmenting Performance in Extreme Environments). Ken explains that this project aims for real time assessment of a special operator’s cognitive performance over long-duration missions, often in extreme environments, as well as developing wearable devices and an integrated system that will help warfighters overcome fatigue and stress by continually sensing and assessing their performance. [01:08:28] Ken asks Josh about his use of the Smartabase platform, which is a commercial human performance optimization platform used for sports teams, military, and other organizations. Ken also asks why Josh is a fan of this platform and what it offers. [01:12:45] Morley closes the interview by asking Josh how someone goes from working for a private company developing spearmint and other flavors to working with elite warfighters and athletes.Links:
Episode 155: Chris McCurdy discusses kratom’s benefits and possible risks
Today we have the world’s foremost authority on kratom returning to STEM-Talk after five years to give us an update on his research. Shortly after his 2018 interview on episode 61, Dr. Christopher McCurdy and his lab at the University of Florida received two major grants from the National Institute of Drug Abuse to investigate the medical efficacy of kratom and its alkaloids, which we discuss in today’s show.
Mitragyna speciosa, or kratom, is an herbal leaf from a tropical evergreen tree in the coffee family. It is native to Southeast Asia where it has been used in herbal medicine for hundreds of years. Kratom has become increasingly popular in the United States and throughout the world for recreational purposes. But kratom is also becoming recognized in the medical and research communities for its treatment for chronic pain as well as its potential to alleviate opioid withdrawal symptoms.
For more than 25 years, McCurdy has studied the design, synthesis, and development of drugs to treat pain, anxiety, and substance-abuse disorders. For the past 15 years, Chris and his lab have turned a lot of their attention toward kratom and its chemical components to better understand its potential to treat a multitude of conditions.
Chris is a professor in the Medicinal Chemistry Department in the College of Pharmacy at the University of Florida. He also is director of the of school’s Translational Drug Development Core and an Associate Dean for Faculty Development.
Our interview with Chris comes on the heels of Florida passing the Kratom Consumer Protection Act, which mandates that kratom products sold in the state meet a high standard of product purity. In today’s interview, we talk to Chris about the protection act as well as:
— The numerous studies he has been able to conduct thanks to his lab’s two grants from the National Institute of Drug Abuse.
— The disparity between the traditional use of kratom and the new often highly concentrated manufactured products sold in the U.S.
— His lab’s study examining the effects of lyophilized kratom tea and its ability to alleviate withdrawal symptoms of opioid-dependence.
— The potential of kratom alkaloids to serve as treatment of various substance abuse disorders.
— The benefits and risks associated with CBD usage.
Show notes
[00:03:21] Dawn opens the interview welcoming Chris back to STEM-Talk and mentions that his last appearance was episode 61 in 2018. Dawn explains that Chris has devoted much of his research to kratom, or Mitragyna speciosa, which is a traditional Southeast Asian medicine. It has been used by indigenous populations for centuries to increase endurance, enhance mood, treat pain, and mitigate opioid withdrawal symptoms. Dawn asks Chris to give a short overview of kratom and why it is attracting so much attention recently. [00:09:14] Ken mentions that at the time Chris first appeared on STEM-Talk, he was in the process of attracting funding to take a deep dive into kratom, which he has now secured from the National Institute of Drug Abuse. Ken asks Chris to give a general overview of the research they are conducting with this grant and what they are finding. [00:15:19] Dawn mentions that in Chris’s last interview on STEM-Talk, he mentioned that researching kratom was difficult due to a lack of standardization and asks if this has changed. [00:21:11] Ken asks about a Thai product that is a freeze-dried leaf, which is coming to the US market, and if this product is more like what is used in Southeast Asia as opposed to the ground leaf material available in the U.S. market. [00:24:29] Dawn mentions that in 2020, Chris and a colleague published an article in the journal Current Opinion in Psychiatry on the need to address the disparity between the traditional use of kratom and the new often highly concentrated manufactured products sold in the U.S. and other countries. Dawn asks Chris to talk about the points made in this article. [00:32:35] Ken follows up on the previous discussion asking how the alkaloid strength and combination may change not only due to the processing of the kratom leaf material, but also as a factor of time. [00:36:33] Dawn asks about a paper that Chris and his colleagues published in the journal Addiction Biology, which reported on research conducted with rats and looked at two of the major psychoactive constituents of kratom: mitragynine and 7-hydroxymitragynine, with an eye toward understanding their potential therapeutic value as well as their abuse potential. [00:44:12] Ken mentions that in November of 2020, Chris and his team published an article reporting on research examining the effects of lyophilized kratom tea with an eye toward determining if kratom alleviated withdrawal symptoms of opioid-dependence. Ken asks about the findings of this study. [00:50:21] Ken asks Chris what the difference is between the lyophilized kratom tea and other preparations. [00:54:20] Dawn mentions an article that Chris published in January and was tagged by the International Association of Pain Management as its paper of the week. Dawn explains that the paper addressed the potential of kratom alkaloids to serve as treatment of various substance abuse disorders. These alkaloids may serve as a blueprint for the development of novel therapies to treat these disorders. Dawn asks Chris to summarize this paper and its findings. [00:58:51] Dawn shifts the conversation to talk about CBD and explains that the FDA has said that further research needs to be done to determine how much CBD can be consumed before harm is caused. Chris has gone on record saying that we need to balance consumer desire for CBD products with a regulatory framework to ensure safety. Dawn asks Chris about the benefits and risks associated with CBD usage. [01:07:19] Ken asks Chris about a recent bill signed into law called the Florida Kratom Consumer Protection Act, which mandates that kratom products sold in Florida meet a very high standard of product purity. It also establishes labeling requirements and limits sales to consumers aged 21 and older. Ken asks Chris to talk about this legislation and why he was in favor of it. [01:13:13] Dawn closes the interview mentioning that Chris has certainly had a lot on his plate over the past five years. She asks what he foresees for his research over the next five years.Links: