Episode 145: Ken answers questions about hypersonic flight, sentient AI, ketogenic vs Mediterranean diets, and more
It’s time for another Ask Me Anything episode where STEM-Talk cohost Dawn Kernagis asks Ken questions submitted by listeners.
In this episode, Ken and Dawn weigh in on:
— Whether AI is becoming sentient.
— How women in midlife might protect their bodies from the negative effects of a slowing metabolism.
— A Stanford study that compared a low-carbohydrate diet with a Mediterranean diet.
— Whether fasting helps optimize cognitive performance.
— The future of hypersonic technology.
— And a lot more.
If you have a question after listening to today’s episode or any episode of STEM-Talk, email your question to STEM-Talk Producer Randy Hammer at email@example.com.
Show notes[00:02:45] Dawn begins the AMA with a question for Ken that was inspired by the Mark Mattson interview, episode 133. Mark talked about skipping breakfast and in his recent book, “The Intermittent Fasting Revolution,”
Mark points out that bodybuilders often skip breakfast and do their weight training in a fasted state, which has the effect of optimizing both muscle building and cognitive performance. The listener mentions that they feel more cognitively sharp in a fasted state but as soon as they break their fast, they don’t feel as sharp. The listener asks Ken if this is normal.[00:04:35] A listener asks Ken about a recent news story in which a Russian robot broke a boy’s finger during a chess match. The listener goes on to state that several of their friends have jumped to the conclusion that this is proof robots are becoming sentient beings and asks Ken for his take is on this given Ken’s AI background. [00:06:02] A listener asks another AI question, this one regarding the Washington Post’s reporting on a Google engineer who was fired over claims he made while at the company that an AI chatbot he had been testing had become sentient. The engineer claimed in an interview with The Guardian that the chatbot, LaMDA, was afraid of being turned off, had read “Les Miserables” and that it had emotions. Google maintains that LaMDA is merely responding to prompts designed for it. The listener asks Ken what would be an appropriate test for gauging AI sentience and what other thoughts Ken has about this story. [00:08:32] A listener mentions that they have been following the ketogenic diet for 18 months and have lost 40 pounds. Recently they checked their liver enzymes GGT, AST, TSH and found they were elevated above “normal” and their Alpha fetoprotein marker was measured at 10.3. The listener asks Ken what he has learned about the ketogenic diet’s impact on the liver. [00:09:48] A listener asks about a recent paper regarding a Stanford study that compared low-carbohydrate diets with a Mediterranean diet. The listener mentions that in the Stanford study the diets had three similarities – no non-starchy vegetables, no added sugars and no refined grains. The key difference in the diets was that the low-carb diet avoided legumes, fruits, and whole grains while the Mediterranean diet included them. The study measured glucose control and cardiometabolic risk in people with prediabetes and type 2 diabetes. The study found that comparative outcomes did not support a sufficient benefit to justify people avoiding legumes, whole fruits, and whole grains to achieve the metabolic state of ketosis. The listener asks Ken for his thoughts on the study. [00:14:57] A listener mentions in their question that they found the Mike Griffin and Mark Lewis interviews both fascinating and worrying. The listener’s key concern is that China and Russia are ahead of the U.S. in terms of hypersonic capabilities. The listener goes on to mention that they recently saw “Top Gun Maverick” and asks if it is reasonable that someday we will see jets with human pilots that are capable of flying 10-to-20 times the speed of sound, as depicted in the film; or will these sorts of aircrafts need to be operated by AI or humanoids. [00:18:17] A listener sends a question that reads, “They say that 50 is the new 30, but after listening to STEM-Talk, I now know that I can expect my metabolism to fall off the “50-cliff” once I meet the chronological milestone of turning 50 years old.” The listener says it’s her understanding that hormonal changes related to midlife, especially for women, are key drivers of metabolic changes that lead to everything from brain fog to weight gain. The listener would like to know what she and other women can do to ward off the negative effects of aging and a slowing metabolism. [00:19:53] A listener mentions that in the Satchin Panda interview, Dr. Panda says that black coffee in the morning probably won’t break an overnight fast, but that coffee with cream will. The listener goes on to say that they listened to a Dave Asprey podcast in which he said drinking “Bulletproof Coffee” with two tablespoons of butter and two tablespoons of brain octane fuel was okay in the morning because it will elevate a person’s blood ketones to 0.7 millimoles per liter within 30 minutes. The listener asks Ken for his thoughts on this advice. [00:22:33] Dawn closes the AMA with a listener question asking if Dr. Ford has any particular pet peeves that he is willing to share.
Episode 144: Jason Fung on how fasting and a low-carb diet improve insulin resistance and metabolic health
Our guest today is Dr. Jason Fung, a Toronto-based nephrologist, and the best-selling author of “The Obesity Code,” “The Diabetes Code,” and “The Cancer Code.” Jason is best known for his success in combining a low-carb diet with intermittent fasting to help thousands of overweight patients reverse their type 2 diabetes, lose weight, and improve their metabolic health.
Jason is the author of the blog “The Fasting Method” and the co-founder of the Intensive Dietary Management program, an initiative that provides low-carb dietary guidance and counseling on various fasting regimes. Jason is also the co-author with Jimmy Moore of “The Complete Guide to Fasting,” which looks at the history and culture of fasting and how it helps people improve their metabolic health.
In today’s episode, Ken is joined by Visiting IHMC research scientist Dr. Tommy Wood and together, they and Jason discuss:
- How in the beginning of his practice, Jason prescribed insulin for type 2 diabetes patients.
- How a series of landmark studies starting in 2008 changed Jason’s mind about using glucose-lowering medication for type 2 diabetes.
- Jason’s realization that type 2 diabetes is largely a dietary disease and therefore requires a dietary solution rather than a pharmaceutical one.
- The origins of Jason’s Dietary Management program, which counsels overweight and obese patients to follow a low-carbohydrate, high-fat diet to reduce insulin.
- A critique of the “eat less, move more” strategy acclaimed by many obesity experts.
- Mark Mattson’s research into the powerful impact of intermittent fasting on metabolic health and a recent paper that questioned the effectiveness of time-restricted eating when compared to daily calorie restriction.
- Recent research and evidence that fasting during chemotherapy may reduce the side effects of the treatment.
Show notes:[00:02:25] Tommy opens the interview mentioning that Jason was born and raised in Toronto and asks what drew Jason to science as a kid. [00:03:43] Tommy mentions the irony that Jason has written several best-selling books, yet Jason was not fond of English or writing when he was in school. [00:04:53] Ken mentions that after graduating from high school, Jason stayed close to home and attended the University of Toronto, entering into medical school just after turning 19 to study internal medicine, eventually specializing in nephrology. Ken asks Jason what intrigued him about becoming a kidney specialist. [00:06:36] Tommy asks Jason what led him to go to UCLA after medical school for his specialty training in kidney disease at Cedars-Sinai Medical Center. [00:07:37] Tommy mentions that Jason has been practicing clinical nephrology in Toronto since 2001, and that in those early years of his practice, Jason saw patients with type 2 diabetes and prescribed medications to keep their blood glucose low. When that didn’t work, he would prescribe insulin, which is the standard medical practice. Tommy asks what Jason observed during these early years of his practice. [00:09:28] Ken mentions that in 2008, two landmark studies were published, the ACCORD study and the ADVANCE study (a summary of ADVANCE). These studies were followed by two more studies, the ORIGIN and VADT studies, all four of which demonstrated that using blood glucose-lowering medication for type 2 diabetes didn’t necessarily have the expected benefits. Ken asks Jason to talk about how these studies were eye-opening for him and confirmed his own experience in treating patients. [00:16:27] Tommy explains that in 1972 Robert Atkins published the “Dr. Atkins’ Diet Revolution,” which shared his findings on the effectiveness of low-carb, high-fat dieting. Tommy goes on to mention that in the late 1990s, a string of Atkins-styled diet books surged in popularity, with most physicians being opposed due to the conventional wisdom that these high-fat diets would cause heart disease. As a result, several trials were launched in the early 2000s to prove this point. Tommy asks Jason to talk about how these trials revealed that the real story is more nuanced than people might think. [00:20:42] Ken mentions that even though Jason and countless other doctors were appalled at the notion that high-fat diets were being promoted as safe and effective, Jason and other physicians had virtually no nutritional training during their years in medical school. Ken asks if, in hindsight, Jason believes this is something that needs to change. [00:24:49] Tommy explains that Jason’s realization that type 2 diabetes was largely a dietary disease and therefore required a dietary solution rather than a pharmaceutical one led him, along with Megan Ramos, a medical researcher, to establish the intensive Dietary Management program in Scarborough, Ontario, in 2011. The object of this program is to counsel overweight and obese patients to follow a low-carbohydrate, high-fat diet to reduce insulin. Tommy asks about the results of this initiative. [00:28:56] Tommy points out that when when Jason started seeing positive results with his patients losing weight and getting off their medications with a high fat diet, Jason started giving lectures around Toronto. He eventually posted a six-part lecture on the etiology of obesity on YouTube and starting a blog, “Intensive Dietary Management,” which evolved into “The Fasting Method.” This all received good feedback and opened the door for Jason to write a book, “The Obesity Code.” [00:30:43] Ken explains that Jason’s book begins with a critique of the “eat less, move more” strategy acclaimed by many obesity experts. Jason points out in the book that while this sounds like a reasonable approach to weight loss, the approach has generally been ineffecitve. Ken asks Jason to elaborate on this. [00:37:08] Tommy explains that there is substantial experimental evidence that the “eat less, move more” approach is not particularly effective advice for individuals in an environment that promotes being sedentary while surrounded by hyperpalatable, calorie-dense, low-protein food. Tommy goes on to say that this does not imply that an integrated calorie balance model is incorrect, only ineffective. Tommy asks Jason for his thoughts. [00:46:58] Ken mentions that in Mark Mattson’s appearance on STEM-Talk, he talked about his recently published book, “The Intermittent Fasting Revolution: The Science of Optimizing Health and Enhancing Performance.” Ken goes on to say that in this interview Mark talked about a paper he had in the New England Journal of Medicine that highlighted how studies in animals and humans have shown that eating in a six-hour window and fasting for 18 hours has been shown to have positive effects on lifespan and a wide range of chronic disorders including obesity, diabetes, cardiovascular disease, cancers, and neurodegenerative brain diseases. However, a recent paper that appeared in the same journal reported that a year-long study among patients with obesity found that a regimen of time-restricted eating was not anymore beneficial – with regard to reduction in body weight, body fat, or metabolic risk factors – than daily calorie restriction. Ken asks Jason for his opinion on this recent study. [00:55:54] Ken mentions that Jason’s answer has circled back to efficaciousness versus effectiveness, and asks if Jason would agree that fasting is a more effective method than calorie restriction to lose weight because it is easier to follow. [00:57:52] Tommy asks if Jason agrees that calorie restriction is efficacious but not effective because it is hard for people to follow. [00:58:45] Tommy asks Jason about his third book in what has been referred to as the wellness series, “The Cancer Code.” [01:02:35] Ken explains that there is obviously a genetic aspect to cancer, but our environment also plays a huge role in the development of cancer. Jason points out in his book that a Japanese woman who moves from Japan to San Francisco often doubles and or triples her risk of cancer. Ken asks what makes the environment of the U.S. such a risk factor, and what makes the environment in Japan protective. [01:05:47] Ken mentions that there is also evidence that fasting during chemotherapy may reduce the side effects of the treatment. Ken asks Jason to talk about this and how fasting might also increase the efficacy of chemotherapy. [01:07:50] Tommy mentions that he understands that Jason weighs the same as he did in high school, and asks what his diet and fasting protocol look like. [01:11:15] To wrap up the interview, Ken asks Jason for his take on rapamycin and concerns about the risk-reward ratio of using rapamycin as a prescription medication.
Episode 143: Ben Bikman on the roles of insulin and ketones in metabolic function
Today’s episode features the author of “Why We Get Sick,” Dr. Ben Bikman, a biomedical scientist at Brigham Young University.
Ben is known for his research into the contrasting roles of insulin and ketones as key drivers of metabolic function.
In “Why We Get Sick,” Ben takes a deep dive into insulin resistance and metabolic health. The book particularly focuses on the role that insulin resistance plays in many of today’s most common diseases: heart disease, diabetes, cancer, and Alzheimer’s.
Ben and his colleagues at the Bikman Lab investigate the molecular mechanisms behind the increased risks of disease that accompany obesity and excess visceral fat. Much of the research at the Bikman Lab particularly focuses on the etiology of insulin resistance and how it disrupts mitochondrial function.
In today’s interview, STEM-Talk cohosts Drs. Ken Ford and Dawn Kernagis talk to Ben about:
- How insulin resistance is tied to multiple chronic diseases.
- The relevance of ketones in mitochondrial function.
- How so many of our modern chronic diseases are self-inflicted and driven by insulin resistance.
- How many of the hallmarks of aging are a consequence of insulin resistance.
- The theory that the longest-lived people are likely the most insulin sensitive.
- The benefits that occur with carbohydrate reduction as a result of increasing insulin sensitivity.
- Ben’s thoughts about the degree of intermittent fasting needed to induce autophagy in humans.
Show notes:[00:02:32] Dawn begins the interview asking Ben about his early life growing up in a small farm town in southern Alberta, Canada, as one of 13 children. [00:02:48] Dawn asks Ben what he was like as a kid and what made him stand out from his 12 brothers and sisters. [00:06:01] Dawn asks about Ben’s mother’s influence and how she wanted her sons to be Renaissance men. [00:08:29] Ken asks about Ben’s experience as a Church of Jesus Christ of Latter-Day Saints Missionary in Samara, Russia. [00:15:18] Dawn mentions that while Ben went into his undergrad majoring in exercise science, he wasn’t that interested in science at the time. It wasn’t until he began working on his master’s degree at BYU with Dr. Will Winder that he developed a true interest in science. [00:19:49] Dawn asks Ben how he ended up at East Carolina University for his Ph.D. in bioenergetics. [00:21:42] Ken mentions that Ben, after completing his Ph.D. moved to Singapore for his postdoc work at the Duke National University of Singapore. Ken asks how that came about. [00:25:49] Dawn mentions that Ben is well-known for his work on insulin resistance, stemming from his time at East Carolina when he realized that insulin resistance is tied to many different chronic diseases. Dawn asks what was Ben’s ah-ha moment that led him to focus his research on insulin resistance. [00:27:49] Dawn mentions that much of Ben’s work is focused on the role of elevated insulin in regulating obesity and diabetes, as well as the relevance of ketones in mitochondrial function. Dawn asks if it is correct that Ben has been on a sort of mission as a professor to teach a new generation of doctors and nurses how insulin resistance works, and why it is so relevant in terms of chronic disease. [00:29:56] Ken mentions that Ben began to take his message about insulin resistance beyond the classroom, appearing on podcasts and making YouTube videos, and also giving a speech to the student body at BYU, titled “The Plagues of Prosperity” making the case that the human race is currently eating itself into metabolic disarray. [00:32:31] Ben’s book “Why We Get Sick” points out that historicall, people got sic because of infectious diseases. In modern times, due to sanitation, vaccines, and antivirals, that is less of an issue. Today more people are afflicted by chronic illnesses, many of which are related to metabolism. Dawn explains that the overarching message of the book is that these diseases are, in part, self-inflicted, and partially driven by insulin resistance and hyperinsulinemia. Dawn goes on to say that while it is fairly well-known that insulin resistance plays a role in cancer, heart disease, and diabetes, many people may not know that it also contributes to neurological disorders, reproductive health, kidney disease, gastrointestinal disorders, and even reduced muscle mass, bone loss, and even hearing loss. [00:34:42] Ken explains that Ben has often pointed out that many of the hallmarks of aging are partially a consequence of insulin resistance. Ben has also pointed out in his book the theory that the longest-lived people are likely the most insulin sensitive. Ken asks Ben to elaborate on this. [00:41:36] Ken mentions that in Ben’s book, he explains that there are three primary causes of insulin resistance, the most obvious one being chronically elevated insulin levels. In addition to this, however, the second category is stress hormones including cortisol and epinephrine. The third cause is inflammation. Ken asks Ben to elaborate on these three causes. [00:45:15] Dawn asks Ben to talk about why our healthcare system has a glucose-centric view of metabolic health. [00:50:26] Ken points out that there’s a lack of consensus on what optimal levels of insulin should be. He also points out that most Americans do not have optimal levels of insulin since most are metabolically unhealthy. Ken asks Ben for his thoughts on what a person’s optimal level of insulin should be. [00:53:34] Ken brings up the problem with the reliance on “normal” readings since unhealthy people skew the average and therefore what is considered normal. Ken asks Ben to talk about how this leads to people who are ketogenic being flagged by their physicians because their insulin levels are low according to their charts. [00:59:25] Dawn asks Ben why he believes building and using muscle is a key component in the fight against insulin resistance. [01:01:03] Dawn mentions that Ben advises people to control carbohydrates, prioritize protein, and “fill with fat.” Dawn asks about the numerous benefits seen with carbohydrate reduction via increasing insulin sensitivity and lowering hyperinsulinemia. [01:03:55] Ken asks Ben to give a quick primer on the process of autophagy, with respect to intermittent fasting. [01:07:54] Ken mentions that a lot of the research about autophagy and fasting uses rodent models. Autophagy is activated much more quickly and to a much greater extent in rodents than in humans. In light of that, Ken asks Ben if we know to what degree intermittent fasting induces autophagy in humans and how long a fast would have to be to incur that effect. [01:11:01] Ken asks Ben to explain how the standard American diet drives fat storage in the body and slows a person’s metabolic rate. [01:16:53] Dawn brings up that recent studies have shown that ketones are not only viable fuel sources for all cells with mitochondria but are also legitimate signaling molecules that elicit advantageous changes in inflammation, cognition, oxidative stress, and more. Additionally, ketones may be relevant metabolic fuel in the context of physical activity and athletic performance. Dawn mentions that further exploration of this can be found in episode 94 of STEM-Talk with John Newman on the topic of beta-hydroxybutyrate, or BHB, and episode 54 with Briana Stubbs on the topic of ketones and athletic performance. Dawn goes on to mention that in a paper published by Ben in 2018, in a special issue of the International Journal of Molecular Science, Ben wrote about the effects of ketones on metabolic function. He reported on the results of a study that sought to shed light on the specific effects of the ketone body BHB on muscle cell mitochondrial physiology. Dawn asks Ben to walk listeners through the results of this study and its implications. [01:20:54] Ken mentions that looking at the role of ketones on the maintenance of muscle, it appears that ketones have less of an anabolic role and more of an anti-catabolic role, which produces a strong protective effect against sarcopenia. Ben talks about this. [01:23:02] Ken mentions that we could make a serious dent in our obesity and type-2 diabetes epidemics if people would think more seriously about insulin and if more physicians tested for it. Ken asks Ben what research, in this regard, are he and his colleagues excited for on the near-term horizon. [01:27:03] Dawn shifts topics to ask Ben what his exercise routine looks like. [01:30:29] Dawn closes the interview by asking Ben if he still plays any instruments.
Episode 142: Vyvyane Loh discusses weight management, ketogenic diet, and the treatment of metabolic diseases
Our interview today is with Dr. Vyvyane Loh, a board-certified physician in obesity and internal medicine. She is the founder and leader of Transform Alliance for Health, a Boston preventive-care practice that specializes in weight management and the treatment of chronic metabolic diseases such as diabetes, hypertension and dyslipidemia.
She and her staff are known for helping people lose 50 pounds or more and getting their type-2 diabetic patients off their many medications. Vyvyane has spent her medical career developing expertise in immunology, metabolic syndrome, fat metabolism, clinical nutrition, and preventive medicine.
In today’s interview, we discuss how abdominal, or visceral, fat is linked to a wide range of metabolic disorders. Vyvyane goes on to explain how there’s a clearcut association between obesity and decreased brain volume that rarely gets discussed. When her overweight patients complain about their behavior around food and how they consistently give in to snacks that patients know are bad for them, Vyvyane explains how the challenges they are facing is often a result of the brain struggling with decreased blood flow and the shrinkage of neurons.
Vyvyane also shares how a patient asked Vyvyane if she knew anything about the Atkins diet, and although she didn’t, Vyvyane ended up doing the diet along with her patient. This led Vyvyane to start seriously researching whether a ketogenic diet could help people not only lose weight, but also reverse chronic disease.
Toward the end of today’s interview, we explore Vyvyane’s interest in macrophages, which are specialized cells involved in the detection and destruction of bacteria and other harmful organisms.
We also have a nice discussion about how Vyvyane took some time off from practicing medicine to enroll in the writing program at Warren Wilson College in North Carolina in 1999. She spent the next two years writing a novel, “Breaking the Tongue.” Set in Singapore during World War II, her book was nominated for the prestigious International IMPAC Award in fiction and was selected by the New York Public Library as one of its top 25 books of 2004.
If you are interested in finding out more about Vyvyane, check out her website, vyvyanelohmd.com. Also, Vyvyane launched a podcast this week, which you also can find on her website. Episode one looks at “Metabolism: What It Is, And How It Affects Your Health.”
If you enjoy today’s interview with Vyvyane and the many other interviews we’ve had on STEM-Talk discussing the treatment and prevention of chronic metabolic diseases, you may want to check out the upcoming virtual conference on Targeting Metabesity.
Our cohost Dr. Ken Ford will be one of nearly 70 speakers, including many former guests on STEM-Talk, talking about the growing evidence that the major chronic diseases of the day share common metabolic roots and as a result may also share common solutions.
To find out more about the conference, follow this link to the Targeting Metabestiy home page where you find a program guide and list of speakers. If you would like a free ticket to the conference, click on this link where you will find instructions on how to receive a code for complimentary admission that is being offered to STEM-Talk listeners.
Ken will be moderating a session on emerging research related to endogenous and exogenous ketosis in health and disease as well as the role of ketones in mild traumatic brain injury and the prevention and treatment of cancer.
If you have enjoyed the interviews we’ve had on STEM-Talk with Drs Steven Austad, Colin Champ, James Kirkland, John Newman, Brianna Stubbs, Jeff Volek and Morley Stone, who are all speaking at the conference as well, you should find the talks by the over 70 speakers quite interesting and beneficial.
So, click here to request a free registration and we will make sure to send a you a code for a complimentary ticket.
Show notes[00:04:45] Dawn mentions that, based on the interviews she’s listened to with Vyvyane, that writing and dance have been passions of hers since she was a child. Dawn then asks Vyvyane at what point did she become interested in science. [00:05:25] Dawn asks Vyvyane how she ended up in the states attending Boston University. [00:06:25] Ken asks why Vyvyane decided to double major in biology and classics. [00:08:14] Ken mentions that Vyvyane’s classics advisor has a connection to the town of Seaside, near where IHMC is located. [00:09:01] Dawn shifts topics to talk about Vyvyane’s research, and asks about TOFI, which stands for “Thin Outside, Fat Inside.” It refers to people who outwardly appear thin, but have a disproportionate amount of adipose tissue in their abdomen, as well as “normal weight obesity.” [00:10:58] Ken mentions that the TOFI phenomenon helps to highlight the relative lack of utility of BMI, which is just a function of the relationship between a person’s height and weight, meaning that people with TOFI will look fine in terms of BMI, and someone who is lean and muscular may be categorized as obese by BMI, particularly if they are not very tall. Ken asks Vyvyane to elaborate on this. [00:12:26] Dawn explains that abdominal, or visceral, fat is of particular concern because it’s a key player in a variety of health problems, more so than subcutaneous fat. She goes on to explain that visceral fat is found deep within the abdominal cavity, where it pads the spaces between our organs. Dawn asks Vyvyane to talk about how visceral fat is linked to a wide range of metabolic disorders. [00:14:37] Ken explains that obesity often causes endothelial dysfunction, which results in the vasculature being inflamed and damaged, resulting often in decreased blood flow to the brain. Ken asks Vyvyane to talk about her frustration with the fact that this clearcut association between obesity and decreased brain volume rarely gets discussed. [00:17:22] Dawn mentions that it is estimated that just 12 percent of Americans are categorized as metabolically healthy. She goes on to mention that researchers at the University of North Carolina published a study that found that just one in eight American adults have optimal metabolic health. [00:18:22] Ken asks Vyvyane what she has learned about metabolic disease in her practice that she didn’t learn in medical school or her residency. [00:19:10] Dawn asks about the prevalence of using food to relieve stress in the wake of the COVID-19 pandemic, and what effects of this trend Vyvyane has seen in her practice. [00:20:13] Ken asks about Vyvyane’s practice, which she started in 2015 because she had been working in the medical system and came to the realization that she couldn’t develop a new way of providing preventive care from within the system. [00:21:53] Dawn mentions that Vyvyane’s practice is called the Transform Alliance for Health, and the website is quoted as saying: “Chronic stress and emotional issues commonly lead to using food to self-medicate or self-soothe. The visible result, the patient’s weight, becomes the focal issue for their healthcare providers. For us, however, it is merely the physical manifestation of the patient’s internal struggle with his/her real problem. From this starting point, we work with our patients to uncover their deeper and often more complex reasons for overeating and to take charge of their lives.” Vyvyane elaborates on this approach to her practice. [00:23:29] Dawn mentions that she listened to an interview with Vyvyane where she talked about how a ketogenic diet can often reduce inflammation and reverse metabolic disease, but that it can be hard to get people to stick to a ketogenic diet. Dawn asks if this is why Vyvyane emphasizes going on a low carb diet for her patients rather than a strict ketogenic diet. [00:25:07] Ken asks about the struggles of having to convince patients to give up carbs. [00:27:17] Dawn explains that non-alcoholic fatty liver disease is today one of the most common maladies in the United States, with a remarkable 30 to 40 percent of adults in this country having it. Dawn asks Vyvyane to discuss NAFLD and what she sees as its causes and the most efficacious treatments. [00:29:07] Dawn asks about the markers Vyvyane uses in evaluating a patient’s metabolic health, including insulin resistance scores and advanced lipid panels. [00:31:45] Ken asks about the curriculums Vyvyane offers for her patients, which explain to them the importance of sleep and mobility and strength training as a way of pressing the body’s “the reset button.” [00:34:00] Dawn mentions that we recently had Greg Potter and Jeff Iliff on the podcast to talk about the importance of sleep and particularly how a lack of sleep can lead to many negative health outcomes. Dawn goes on to mention that something Vyvyane has emphasized in the past is the role of nocturnal blood pressure dipping during sleep. Dawn asks Vyvyane to explain what she means by that, and how a lack of it increases a person’s risk for silent strokes and kidney dysfunction. [00:35:45] Ken asks Vyvyane to talk about her recommendations for protein intake as it relates to body composition and sarcopenia. [00:39:18] Ken asks Vyvyane to talk about some of the immune cells that are involved in regulating metabolic health. [00:41:34] Dawn mentions Vyvyane’s recent lecture at IHMC, titled “On the Magical Mystery Macrophage Tour, where she refers to macrophages as mysterious, specialized cells of innate immunity that play significant roles in some of our most common medical conditions ranging from cardiovascular disease to gastrointestinal disorders to obesity to osteoarthritis. Vyvyane elaborates on what these cells are and their various functions. [00:43:02] Ken asks how and when Vyvyane first became interested in macrophages. [00:43:41] Ken mentions that macrophages also stand out because they possess the unique ability to become polarized in response to different environmental stimuli and asks Vyvyane to explain how this works. [00:46:22] Dawn explains that macrophages can detect products of bacteria and other microorganisms using a system of recognition receptors such as toll-like receptors or TLRs. Vyvyane explains the role and significance of these receptors. [00:48:13] Dawn mentions that tissue-resident macrophages, or TRMs, are heterogeneous populations originating either from monocytes or embryonic progenitors and distribute in lymphoid and non-lymphoid tissues. Dawn asks Vyvyane to talk about the diverse roles that TRMs play in many physiological processes, including metabolic function. [00:50:46] Ken mentions that current medical practice still looks at obesity through the lens of caloric balance. Ken asks what new discoveries in obesity research challenge that dogma. [00:54:39] Dawn asks about the aspects of Vyvyane’s life outside of her medical practice such as writing, dance, and choreography. [00:55:47] Ken mentions that Vyvyane’s novel, “Breaking the Tongue,” was selected as one of the Top 25 Books of 2004 by the New York Public Library and in 2006 was nominated for an International IMPAC Award, which is the world’s richest prize for a single work of fiction published in English. Ken explains that the novel chronicles the fall of Singapore to the Japanese in World War II, and asks Vyvyane to talk about the book and how it deals with issues of race and class. [00:58:08] Ken mentions that Vyvyane has another novel she is working on, but that it, and her fiction writing as a whole, is on hold because she is working on a nonfiction book. Ken asks Vyvyane to talk about this new book. [00:59:47] Dawn closes the interview asking about Vyvyane’s morning routine, which incorporates an hour of meditation. Dawn also asks what else Vyvyane does on a regular basis.
Episode 141: Jeff Iliff on newly discovered system that clears waste from the brain
Our guest today is Dr. Jeffery Iliff, a professor of psychiatry and behavioral sciences in the Department of Neurology at the University of Washington. Much of Jeff’s research focuses on neurodegeneration and traumatic brain injury.
He is the associate director of research at the VA Puget Sound Health Care System and a co-leader for research at the University of Washington’s Alzheimer’s Disease Research Center.
In this episode, we talk about Jeff’s investigations into the glymphatic system, which is a newly discovered brain-wide network of perivascular spaces that facilitates the clearance of waste products from the brain during sleep. Jeff goes on to describe how he is exploring how the glymphatic system fails in the aging brain as well as in younger brains after traumatic brain injury.
Jeff and Dawn also have a conversation about their collaboration on a research project that’s focused on how extreme stressors impact the glymphatic system. Together they are investigating a potential approach to optimizing glymphatic clearance for individuals with acute or chronic sleep deprivation.
Show notes:[00:02:55] Dawn opens the interview asking Jeff where he grew up. [00:03:21] Dawn asks what Jeff what he was like as a kid. [00:04:01] Ken mentions that it wasn’t until Jeff was working as a lifeguard at a boy scout camp that he first became interested in science. Ken asks Jeff what it was about his lifeguard experience that triggered the interest. [00:05:06] Dawn asks what led Jeff to the University of Washington as an undergrad. [00:06:02] Ken mentions that Jeff originally intended on going into pre-med. Ken explains that Jeff changed his mind and asks about a suggestion from a girlfriend that caused Jeff to have a change of heart. [00:07:39] Dawn points out that in addition to working in the lab as an undergrad, Jeff also worked a 48-hour shift as an EMT over the weekends. Dawn asks Jeff why he kept such a busy schedule. [00:09:35] Ken asks what led Jeff to the Oregon Health & Science University for his Ph.D. [00:10:53] Dawn asks if it’s true that Jeff’s wife played a big role in his decision to travel across the country to New York for his post-doc at the University of Rochester. [00:13:06] Dawn mentions that after the second year of Jeff’s post-doc, he was promoted to a junior faculty position because he was part of the team that discovered a brain cleaning system known as the glymphatic system. The team published a paper in 2012 in science translational medicine that was the first of about ten papers that later became known as the “glymphatic papers.” After a follow-up paper in 2013, Science Magazine cited the discovery that the glymphatic system cleans the brain during sleep as one of the “Top 10 Breakthroughs of 2013.” Dawn asks what this experience was like for Jeff as a young post-doc and junior faculty member. [00:15:55] Dawn explains that the lymphatic system is a network of vessels extending throughout most of the body that transport excess fluid and waste from the interstitial spaces between cells to the blood. She goes on to explain that these vessels are notably not found in the brain leading to the question of how interstitial fluid is cleared in the brain. Jeff’s team discovered the glymphatic system, which serves the same function in the brain as the lymphatic system in the rest of the body. This discovery turned out to be a paradigm shift and led to numerous subsequent studies. Dawn asks Jeff how the initial 2012 study came about and how they identified a distinct clearing system in the brain that serves a lymphatic function. [00:19:59] Dawn mentions that after Jeff’s initial work in the glymphatic system, he went on to write what has become known as his sleep paper. Dawn goes on to say that for this study, Jeff used two-photon microscopy to visualize fluid moving in and out of the brain, and at some point, saw his tracer leaving the brain. Dawn asks Jeff what this experience was like. [00:23:55] Ken asks Jeff to explain the relationship between sleep cycles and the glymphatic system. [00:26:33] Jeff explains some of the differences in sleep between mice and humans. [00:28:35] Ken asks if the critical role of slow-wave sleep in glymphatic function and clearance explains the potential relationship between sleep deprivation and increased risk of neurodegenerative disease. [00:31:29] Ken asks about the impact of sleep deprivation of normal cognitive function. [00:32:43] Ken asks if there is any research on the glymphatic function of APOE4 carriers. [00:35:33] Ken asks about work done by Jeff’s postdoc mentor, Maiken Nedergaard, that suggests that glymphatic function can even be impacted by sleep that is outside the normal circadian rhythm, potentially explaining the increased risk of neurodegenerative disease in shift workers. [00:38:50] Dawn mentions that Jeff’s 2013 sleep paper became the predecessor for many subsequent neuro-imaging studies looking at glymphatic function in the human brain, leading to the pursuit of new neuro-imaging techniques for the measurement of glymphatic function and asks about the developments in this area. [00:42:36] Ken asks about Jeff’s 2014 paper in the Annals of Neurology, in which he proposed that impaired glymphatic clearance contributes to cognitive decline among the elderly and may represent a novel therapeutic target for the treatment of neurodegenerative diseases associated with the accumulation of misfolded protein aggregates. [00:46:44] Ken asks if there is thought to be a connection between glymphatic function and other disorders like Parkinson’s, vascular dementia, etc. [00:48:45] Dawn asks about the meningeal lymphatic system, which consists of lymphatic vessels running parallel to the dural venous sinuses and middle meningeal arteries, and how it relates to the glymphatic system. [00:52:01] Ken asks Jeff why he thinks the glymphatic system had not been identified until recently. [00:54:48] Ken asks about Jeff’s move from the University of Rochester back to Oregon, and how Phil Knight, founder of Nike, played a role in this decision. [00:56:14] Dawn mentions that Jeff was at Oregon for six years, but during this time became connected with a research group at the VA Puget Sound Health Care System in Seattle, which is an affiliate of the University of Washington. Dawn asks what led Jeff to return to Washington, where he currently works as a professor in the Department of Neurology and is the Associate Director for Research at the VA Center, as well as what he and his research group are currently studying. [01:00:24] Ken asks how traumatic brain injury (TBI) affects the glymphatic system. [01:02:44] Dawn mentions that in TBI, Aquaporin-4, or AQP4, is a water channel expressed in astrocytes throughout the central nervous system as well as in epithelial cells in various peripheral organs. The expression of this protein changes in the setting of TBI. She goes on to explain that AQP4 is involved in brain water balance, neuroexcitation, astrocyte migration, and neuroinflammation and is the target of pathogenic autoantibodies in neuromyelitis. Jeff’s 2017 paper in JAMA Neurology looked at how altered AQP4 was associated with aging brains. Dawn asks about this paper, and the implications that the loss of perivascular AQP4 localization may be a factor that renders the aging brain vulnerable to the misaggregation of proteins in neurodegenerative conditions such as Alzheimer’s. [01:05:30] Dawn mentions how the collaboration between her and Jeff’s teams involves working on several studies involving human glymphatic imaging in different settings. Dawn asks Jeff to explain the efforts in validating a non-invasive contrast-free imaging approach to visualizing glymphatic function in humans. [01:08:30] Ken asks Jeff to explain why validating new imaging approaches against intrathecal contrast MRI is so important for the clinical and research communities. [01:12:06] Dawn explains that the first study she and Jeff officially started working on together is funded by the Office of Naval Research, and kicked off in 2021. In this study, they are assessing the impact of extreme environmental conditions on glymphatic function in humans, ranging from hypoxia, hypercapnia, and hyperoxia. Dawn asks Jeff to talk about the status of these studies and their impact on future human glymphatic research. [01:16:28] Dawn asks about a paper Jeff and his team published on astronaut brains post-flight and whether fluid-filled spaces in the brain, known as perivascular spaces, are enlarged post-flight. [01:19:41] Dawn mentions that one of the biggest questions she gets about the glymphatic system is if it can it be ‘fixed’ to function better if it has been impaired. Dawn asks Jeff how he would answer this question based on the current state of research. [01:21:46] Dawn asks Jeff if there are any nutritional or exercise approaches that might help improve glymphatic function. [01:22:53] Ken asks if Heart Rate Variability (HRV) plays a role in glymphatic function. [01:24:52] Dawn mentions that her and Jeff’s collaboration has expanded to include Dr. Miranda Lim at Oregon Health and Science University, Dr. Don Tucker at the Brain Electrophysiology Lab, and Dr. Jeffrey Heys at Montana State University. They are working on DoD funded study to look into a device that could potentially stimulate the glymphatic system in individuals who are acutely or chronically sleep deprived. [02:27:10] Ken asks what should the next key studies in glymphatic research focus on. [01:29:29] Dawn asks if Jeff still takes time off from his lab work to go watch his son’s baseball games and his daughter’s softball games. [01:30:22] Ken asks if it’s true that Jeff is a huge fantasy football fan, and that when he was a post-doc fellow, he and some colleagues started a fantasy football league that is still going on all these years later. [01:32:15] Dawn says she assumes Jeff is a Seattle Seahawks fan and asks Jeff if he ever had Russel Wilson on his fantasy football team. [01:33:15] Ken asks if it is true that Jeff’s students are fans of STEM-Talk. [01:34:19] Dawn closes the interview telling Jeff to let his students know to write a review of this episode so they can get a free STEM-Talk t-shirt.
Episode 140: Kaleen Lavin on the benefits of exercise on Parkinson’s and “inflammaging”
Today we would like to introduce you to one of our newest colleagues here at IHMC, Dr. Kaleen Lavin, a research scientist who investigates the molecular mechanisms by which the body adapts and reacts to stressors such as exercise, training and aging.
Kaleen came onboard at IHMC last year and is known for her use of computational biology techniques as a means to understand and improve human health, performance and resilience.
She also is interested in the use of exercise as a countermeasure for a range of disease conditions, including neurodegenerative diseases such as Parkinson’s disease. Today we will talk to her about some of her most recent work that examined the molecular effects of exercise training in skeletal muscle and in people with Parkinson’s.
We also talk to Kaleen about her recent paper that took a comprehensive look at the current literature surrounding the molecular and cellular processes underlying the molecular benefits that exercise induces in humans. The paper appeared earlier this year in Comprehensive Physiology and was titled, “State of Knowledge on Molecular Adaptations to Exercise in Humans.”
Kaleen is a graduate of Georgetown University, where she earned a bachelor’s degree in biology. She also earned a master’s in sports nutrition and exercise science from Marywood University in Pennsylvania and a Ph.D. in human bioenergetics from Ball State University in Indiana.
Show notes:[00:03:02] Dawn opens the interview mentioning that Kaleen grew up in Scranton, Pennsylvania, and asks Kaleen about her passion for music as a youth. [00:03:25] Ken asks Kaleen about her high school years and how she became a competitive swimmer. [00:04:26] Dawn mentions that Kaleen was an excellent student growing up, but that it wasn’t until her junior year of high school that she became interested in science. Dawn asks if it were a teacher who inspired Kaleen. [00:05:21] Dawn asks what led Kaleen to attend Georgetown University after graduating from high school. [00:05:57] Dawn asks if Kaleen knew she wanted to major in biology when she first arrived on campus at Georgetown. [00:06:45] Ken asks about Kaleen’s experience of becoming a part of the Howard Hughes Program at Georgetown, which led to her gaining experience working in lab. [00:08:47] Dawn mentions that Kaleen transitioned from competitive swimming to running during her undergraduate years, running a marathon and half marathon. Dawn asks if Kaleen’s father, who is an avid marathoner, gave her the incentive to start signing up for marathons. [00:13:19] Dawn asks Kaleen about a faculty advisor who noticed her passion for running and exercise and helped her decide what to pursue for her master’s degree. [00:15:23] Ken asks Kaleen what led her to pursue her master’s at Marywood University, a small Catholic University in Scranton. [00:16:56] Ken asks Kaleen what prompted her to pursue a Ph.D. in exercise science at Ball State University, which has one of the longest-standing human performance programs in the country. [00:17:57] Dawn mentions Kaleen’s experience with no-breath laps as part of her training when she was in high school on the swim team. Dawn asks Kaleen to explain what no-breath laps are. [00:19:00] Dawn asks Kaleen about a study she conducted for her master’s thesis at Marywood that examined the effects of controlled frequency breath swimming on pulmonary function. [00:22:13] Ken asks about how Kaleen’s time at Ball State set her up for her post-doc work at Center for Exercise Medicine at the University of Alabama at Birmingham. [00:24:31] Ken asks what it was about UAB that attracted Kaleen to do her post-doc work there. [00:26:08] Dawn asks about a study published in 2017 by a group at UAB led by Marcas Bamman where researchers took people with Parkinson’s disease and ran them through a high-intensity exercise program, finding that you could not only help people preserve some function but also restore some function. [00:28:52] Ken mentions that despite the awareness of Parkinson’s negative impact on motor function, there has been very little attention paid to its impact on skeletal muscle. Ken asks Kaleen to talk about her study that provided insights into the potential mechanistic roles of skeletal muscle. [00:31:33] Dawn mentions that the research Kaleen just discussed was published in a paper titled “Rehabilitative Impact of Exercise Training on Human Skeletal Muscle Transcriptional Programs in Parkinson’s Disease.” [00:31:51] Kaleen talks about her analysis of the dataset from the 2017 study at UAB that was led by Marcus Bamman. Kaleen explains how she was able to identify 706 genes that were differently expressed after rehabilitative training, and how this work strengthens our understanding of skeletal muscle as a communicative tissue in exercise, aging, and neurodegenerative disease. [00:33:38] Dawn asks Kaleen to elaborate on how she ended her paper talking about how future research is needed to determine the influence of exercise training on other levels of phenotypes in Parkinson’s Disease and how skeletal muscle may reflect or orchestrate these changes. [00:35:31] Ken asks Kaleen to talk about her plans for a future clinical trial concerning Parkinson’s at IHMC. [00:37:21] Dawn asks about another study Kaleen conducted that looked at why people respond differently to the same exercise. Dawn also asks Kaleen to talk about why the reduction in skeletal muscle mass with advancing age is such a serious issue. [00:39:20] Ken follows up mentioning that sarcopenia is often thought of as a gradual decline in muscle mass, but often it is a process where there will be a slow gradual trend punctuated with large downward spikes as individuals grow older and experience illness and injury over the years. [00:41:01] Ken mentions that for the aforementioned study, Kaleen examined what occurs at the molecular level to shed light on the impact of resistance training on muscle hypertrophy. Ken goes on to explain that, previously, the UAB lab and others had demonstrated the magnitude of resistance-training-induced muscle hypertrophy is highly variable across individuals, a phenomenon known as interindividual response heterogeneity. [00:43:07] Dawn mentions that Kaleen used two algorithms to assess the evidence of gene networks that link muscle building to gene expressions. Dawn asks why Kaleen decided to proceed this way, and what future research possibilities does this method open up. [00:45:20] Ken asks about the possibility that Kaleen’s study leaves open the idea that exercising in the past leaves a molecular footprint, creating a kind of “muscle memory” that can come back to help us as we age, even if we haven’t kept up the habit of exercise. [00:54:39] Dawn mentions that Kaleen’s 2019 study on the effects of aging and lifelong aerobic exercise on inflammation supports other recent evidence that training is anti-inflammatory. Kaleen explains that the lifelong habit of exercise offers protection against “inflammaging,” which is the experience of chronic low-grade inflammation throughout the aging process. Dawn asks, however, if people who have waited till their 30s or 40s to begin the habit of exercise have passed the window of opportunity to benefit from the protective therapeutic factors that regular training confers. [00:55:55] Dawn explains that Kaleen was recently the lead author of a paper that appeared earlier this year in Comprehensive Physiology titled, “State of Knowledge on Molecular Adaptations to Exercise in Humans.” Dawn explains that this paper was a comprehensive look at the current literature surrounding the molecular and cellular processes underlying exercise-induced benefits and adaptations in humans. Dawn asks Kaleen to explain how the study of exercise as a preventative and therapeutic treatment has been rapidly gaining momentum for the past couple of decades. [00:57:58] Dawn mentions that the National Institutes of Health decided to fund a trial to look at the effects of exercise at the molecular level across a large group of people to build what they’re calling the Molecular Map of Exercise. Dawn asks Kaleen to talk about the consortium that the NIH is funding for this trial, and how Kaleen’s paper ties into that. [01:01:46] Ken asks what kind of response this review paper has received from the broader community. [01:02:49] Ken mentions that Marcas Bamman, who is helping spearhead IHMC’s new Healthspan, Resilience and Performance Complex, recruited Kaleen to become part of this initiative. Ken asks Kaleen what attracted her about this project. [01:04:15] Dawn mentions that Kaleen is heading up a lot of the computational work at IHMC to help the institute’s researchers gain insight into why some people respond better to exercise than others on a molecular level. Dawn goes on to mention that Kaleen is currently working on a number of ongoing projects and asks her to talk about how her work plays into all this research. [01:05:44] Kaleen talks about how it’s essential to have the right tools as researchers’ questions become more complicated. She and a colleague at IHMC recently received funding to enhance what is known as a pathway-level information extractor, a tool more commonly referred to as PLIER. Kaleen talks about how the funding for this project will allow IHMC to build up its algorithm potential and open the door for IHMC researchers to handle higher dimensions of data.
[01:07:48] Dawn asks about a paper by a group of researchers out of the Swedish School of Sport and Health Sciences in Stockholm, which examined acute molecular responses to concurrent exercise involving different muscles. [01:09:56] Ken asks if Kaleen thinks that her type of muscle fiber, which is highly skewed toward Type I, has anything to do with her gravitation towards endurance sports [01:11:39] Ken talks about the shift in muscle fiber type seen in the aging population where fast twitch fibers are lost first, leading to some older people maintaining strength but losing explosive power. [01:13:20] Dawn asks if there is a triathlon in Kaleen’s future. [01:14:02] Dawn asks Kaleen about the influence of muscle-fiber type on performance and how that might influence someone in terms of them gravitating toward a particular mode of exercise. [01:15:41] Dawn closes the interview asking about Kaleen’s passion for singing and how she now sings in her church choir.
Episode 139: Matt Kaeberlein discusses healthspan, longevity, and rapamycin
In response to several requests from listeners, we have as our guest today, Dr. Matt Kaeberlein, a professor of pathology at the University of Washington. Matt is well-known for his investigations into the basic mechanisms of aging. Much of his research in this area is focused on identifying interventions that promote healthspan and lifespan.
In today’s interview, we talk to Matt about the biology of aging and what he has learned about slowing the aging process. In 1999, Matt and his colleague Mitch McVey discovered that overexpression of the SIR2 gene is sufficient to extend lifespan in yeast. SIR stands for silent information regulator, and we have an interesting discussion about how Matt’s research and 1999 discovery have elevated SIR2 to the forefront of aging research.
Also, some of Matt’s most recent and fascinating investigations have been into rapamycin, the only known pharmacological agent to extend lifespan. His research has shed new light on the role rapamycin plays in delaying age-related dysfunction in rodents, dogs, and humans.
We also have a fun discussion with Matt about his research showing that rapamycin may have the potential to reduce the mortality of companion dogs. The paper that came out of this research landed Matt on the front page of the New York Times and received prominent play in the national and overseas media.
Other topics we cover include:
- Matt’s attempts to uncover the molecular mechanism behind lifespan extension via calorie restriction.
- His research into mTOR, which is a protein in every cell, and how inhibiting mTOR has been shown to extend the lifespan of insects, rodents, and animals.
- Matt’s 2006 study that showed fasting extends lifespan in worms more than caloric restriction.
- And an article Matt published last year that summarized several of the most popular anti-aging diets, comparing them with classical caloric restriction.
In addition to his work in his Kaeberlein Lab, Matt is the co-director of the Nathan Shock Center of Excellence in the Basic Biology of Aging and the founding director of the Healthy Aging and Longevity Research Institute at the University of Washington. He also is the founder and co-director of the Dog Aging Project.
Show notes:[00:02:53] Dawn asks Matt and his youth and where he grew up. [00:03:06] Ken asks if it is true that Matt spent a good deal of his youth “up to no good.” [00:04:20] Dawn mentions that while Matt got decent grades in school, it wasn’t until he went to college that he became studious. Dawn asks Matt if it true that he had originally decided to skip college. [00:05:42] Dawn asks how Matt ended up in Bellingham at Western Washington. [00:06:41] Dawn asks how in the world, despite not liking high school and working a morning shift at UPS for two years after graduating, Matt decided to head off for college and major in biochemistry of all things. [00:08:01] Ken asks what led Matt to travel across the country to Boston and MIT’s biology program. [00:09:57] Ken asks why Matt decided to focus his research on the biology of aging. [00:11:57] Matt talks about what he did following his Ph.D. [00:13:15] Dawn asks Matt what kind of research he did at the University of Washington Department of Genome Sciences for his post-doc, and how this research related to aging. [00:15:10] Ken mentions that it was during Matt’s undergrad that he decided to focus on the question, “To what extent are the mechanisms of aging evolutionarily conserved?” Ken asks Matt what caused him to arrive at that for his central focus. [00:19:36] Dawn mentions that the discovery by Matt, and Mitch McVey, that overexpression of SIR2 (Silent Information Regulator) is sufficient to extend life span in yeast is credited with promoting SIR2 to the forefront of aging research. Dawn goes on to mention that SIR genes are determinants of life span in yeast mother cells. Dawn asks Matt to give a quick primer on the SIR genes and their functions. [00:20:55] Ken follows up asking about Matt’s 1999 paper that appeared in the journal Genes and Development. Matt talks about this paper and how he demonstrated that increasing the dosage of SIR2 extended lifespan. [00:23:42] Dawn mentions that after Matt arrived at the University of Washington, he began looking at yeast and C. elegans, to see if there were key aspects of aging that could be related to humans. This research led to Matt and his colleagues publishing a paper in 2008 demonstrating quantitative evidence for conserved longevity pathways between different eukaryotic species. Dawn asks Matt to talk about how today most people agree that there are key aspects of aging shared across all animals, even down to yeast. [00:27:27] Dawn asks about Matt’s lab and the work he does at the University of Washington as well as the work he does as the director of the Healthy Aging and Longevity Research Institute as well as the work he does as director of the Nathan Shock Center of Excellence in the Basic Biology of Aging Training Program. [00:30:06] Dawn asks about some papers Matt published in 2004 and 2005, which attempted to uncover the molecular mechanism behind lifespan extension via calorie restriction, which has been seen across a wide variety of animals. Dawn mentions that one of Matt’s 2004 papers disproved the model that caloric restriction acts solely through SIR2 to mediate lifespan extension and asks him to talk about that discovery. [00:36:31] Ken follows up asking Matt to talk more about his TOR and mTOR related work. [00:39:57] Dawn mentions that Matt’s lab followed up these aforementioned papers with a study that showed fasting extends lifespan in worms more than caloric restriction, in which the worms were fasted for their entire adulthood. Matt talks about the findings and implications of this study. [00:43:41] Ken asks about Matt’s research into rapamycin and the role it plays in increasing the lifespan of rodents and delays age-related dysfunction in both rodents and humans. Ken asks specifically about Matt’s 2016 study, the findings of which suggest that short-term rapamycin treatment late in life can not only delay aging but also influence cancer prevalence and modulate the microbiome. [00:47:43] Dawn mentions Matt’s research that garnered the attention of the NY Times, where he began treating dogs with rapamycin and asks what prompted Matt’s interest in studying dogs and aging. [00:51:06] Ken mentions Matt’s article in Nature published earlier this year, where he explained that the primary goal of the Dog Aging Project is to generate and facilitate discoveries on the fundamental biology of aging. He also argued that the impact of the Dog-Aging Project will go far beyond this goal and Ken asks Matt to explain what he meant by that. [00:53:46] Dawn asks about Matt’s recent paper in eLife that looked at whether rapamycin could rejuvenate oral health in mice, and goes on to explain that periodontal disease is prevalent in elderly human populations and currently has no therapy that can effectively reverse it. Matt talks about this study and the promising results from it. [00:56:21] Dawn asks about Matt’s recent review summary that appeared in the journal Science last year that looked at several of the most popular anti-aging diets, comparing them with classical caloric restriction. Matt gives an overview of the interventions evaluated and what insights were gained. [01:01:38] Ken mentions that IHMC has done some studies on ketone esters and asks about Matt’s opinion on findings that suggest that ketone esters by themselves could have antiaging properties. [01:04:59] Ken asks about Matt’s opinion that a case can be made that mTOR complex 1 is a particularly relevant and robust molecular transducer of diet-induced antiaging signals. [01:08:41] Ken asks if mTOR complex 1 is the complex that is involved in muscle protein synthesis. [01:11:31] Ken brings up the point that discussions of mTOR inhibition via rapamycin is often coupled with the idea of inhibition of protein synthesis which leads to confusion regarding the difference between not having enough protein in the diet and inhibiting protein synthesis. Matt brings up the point that transient inhibition of mTOR will have different effects than continued chronic inhibition of mTOR, making dosing and timing important variables in this question. [01:13:08] Ken and Matt discuss the self-experimentation that many people have begun to do with rapamycin. They also discuss the possible interaction of rapamycin and resistance exercise in humans. [01:14:58] Ken asks, based on all the current findings regarding rapamycin, whether Matt thinks we are at the point where people should start seriously considering rapamycin or if more research needs to be done first. [01:17:55] Ken asks if Matt has perceived a benefit from his own personal use of rapamycin. [01:20:06] Dawn asks Matt, as someone who lives by the motto “live long or die trying,” what are the strategies that he uses in terms of diet, supplements, and exercise. [01:23:46] Dawn asks Matt how his dog is doing to close the interview.
Episode 138: Mark Lewis discusses hypersonics and the importance of research in national defense
Today’s guest is Dr. Mark Lewis, executive director of NDIA’s Emerging Technologies Institute (NDIA ETI), a non-partisan think tank focused on technologies that are critical to the future of national defense. ETI provides research and analyses to inform the development and integration of emerging technologies into the defense industrial base. We will discuss the Emerging Technologies Institute’s Vital Signs report, which is an evaluation of the readiness and health of the defense industrial base.
Prior to his role at the Emerging Technologies Institute, Mark was the Director of Defense Research & Engineering in the Department of Defense, overseeing technology modernization for all military services and DoD Agencies, as well as the acting Deputy Under Secretary of Defense for Research & Engineering. In this role he was the Pentagon’s senior-most scientist, providing management oversight and leadership for DARPA, the Missile Defense Agency, the Defense Innovation Unit, the Space Development Agency, Federally Funded Research and Development Centers, and the DoD’s basic and applied research portfolio.
At the Department of Defense, Mark worked closely with Mike Griffin, who appeared on episodes 23 and 134 of STEM-Talk. In today’s interview with Mark, we will again discuss hypersonics and other emerging technologies and modernization priorities that are critical to our national defense.
Mark is also the former longest-serving and is perhaps best known for his work in hypersonics.
In addition to these important defense-related roles, Mark is also a professor emeritus at the University of Maryland. He spent 25 years as a faculty member at Maryland, conducting basic and applied research in hypersonic aerodynamics, advanced propulsion, and space-vehicle design.
Show notes:[00:03:27] Dawn opens the interview asking where Mark grew up and what he was like as a kid. [00:04:29] When Dawn asks Mark when he first became interested in science, Mark tells a funny story form his time as president of the American Institute of Aeronautics and Astronautics? [00:06:21] Ken asks Mark how he ended up at MIT after high school. [00:07:46] Mark talks about taking a job as an assistant professor of aerospace engineering at the University of Maryland after earning his Ph.D. in aeronautics and astronautics at MIT. [00:09:34] Dawn mentions that from 2002 to 2004, Mark was the director of the Space Vehicle Technology Institute. She asks Mark to give an overview of the Institute and the kind of work that goes on there. [00:12:45] Ken mentions that in 2004, Mark became Chief Scientist of the U.S. Air Force, going on to become the longest-serving Chief Scientist in Air Force history. Ken asks Mark to explain the role of the chief scientist, and what he focused on during his time in the position. [00:17:37] Dawn explains that in 2012, Mark became the director of the Science and Technology Policy Institute, which worked with the executive office of the President and other Executive Branch agencies. Mark talks about the kind of work the Science and Technology Policy Institute does. [00:20:23] Dawn mentions that during Mark’s 25 years as a faculty member at the University of Maryland, he conducted basic and applied research in a variety of fields, such as hypersonic aerodynamics, space vehicle design, and advanced propulsion. She point out that Mark, however, is best known for his work in hypersonics. She asks Mark what led him to focus on hypersonics. [00:22:46] Ken asks Mark to explain why he decided to work under Mike Griffin (episodes 23 and 134) in the Pentagon as the Director of Defense Research and Engineering, and what that experience was like. [00:28:19] Dawn mentions that during Mike Griffin’s time as Under Secretary of Defense for Research and Engineering, he made hypersonics the department’s number one priority. Dawn asks Mark to explain the importance of hypersonics in terms of our national defense. [00:33:38] Ken asks Mark when he thinks an air breathing hypersonic tactical round might be available on a production basis. [00:35:40] Ken mentions that Russia recently test-launched the RS-28 Sarmat, a liquid-fueled MIRV-equipped super-heavy intercontinental ballistic missile, sometimes referred to in the west as the “Satan II.” Mark gives his take on the RS-28. [00:39:44] Dawn explains that in 2008, when Mark was concluding his time as Chief Scientist of the Air Force, he launched a study that became known as the Day Without Space Study. This study concluded that we would have a very hard time fighting a war without our relatively vulnerable space assets. Dawn asks Mark to talk about the importance of space in our national defense. [00:43:03] Ken asks Mark about directed energy technology, and its importance in terms of our national defense and weapons capabilities. [00:45:02] Mark discusses his new role as the executive director of the National Defense Industrial Association’s Emerging Technologies Institute, which is a nonpartisan institute focused on technologies that are critical to the future of our national defense. [00:47:28] Dawn asks about the Institute’s ongoing initiative called the Vital Signs Project, which is a report that measures the well-being of the nation’s defense industrial base. [00:48:41] Ken mentions that the 2022 Vital Signs report came out earlier this year with the defense sector receiving an overall poor grade of 69, which is three points below last year’s grade. Ken asks what effect these reports are having. [00:49:50] Dawn explains that in 2022, the authors of the Vital Signs report assigned a failing grade in five areas, with one of the most troubling declines being in supply-chain performance. Dawn goes on to say that the report noted that the decline reflected the turbulence the economy is facing, some of it caused by the COVID-19 pandemic. She also points out that next year’s report is expected to report even greater supply chain issues and she asks Mark to explain why this is such a major problem for the Pentagon. [00:51:57] Ken mentions that another significant drop came in productive capacity and surge readiness. He asks Mark to define what is meant by the term “surge readiness.” [00:54:28] Dawn asks Mark for his take on the fact that U.S. government funding for research and development fell by 12 percent between 2011 and 2016, while in the same time frame China increased its R&D investments by 56 percent. [00:58:54] Ken asks if we are doing a good job of not only researching and developing technologies for our national defense, but also pushing these developments into practical production. [01:02:54] Ken circles back to hypersonics, explaining that the U.S. used to be the world leader in this technology, partly because of our past test-fail approach to innovation. Ken explains that there is a real resistance to that approach to research today in Congress and asks Mark if he believes we need a return to this old mindset for innovation if we are going to catch up with the Chinese and Russians. [01:12:33] Dawn asks what Mark likes to do in his spare time. [01:13:44] Dawn closes the interview and thanks Mark for his time.
Episode 137: Greg Potter discusses lifestyle changes for better health and sounder sleep
Today we return with the second half of our two-part interview with Dr. Greg Potter, a British researcher who specializes in circadian biology, sleep, diet, and metabolism. In this second part of our interview, host Ken Ford and Greg continue their conversation about circadian biology and cover topics ranging from insomnia, sleep apnea, time-restricted eating, exercise, nutrition, and supplementation.
In part one of our interview, episode 136, Ken talked to Greg about how he became interested in circadian biology and the importance of synchronizing our lifestyles to be in tune with our circadian rhythms. Greg also explains why he decided to specialize in sleep and what his research has taught him about the role and importance of melatonin, a hormone that helps control the body’s sleep cycle.
Dawn Kernagis was traveling during our talk with Greg and couldn’t join Ken to co-host the interview. Greg gained attention in the U.S. and Europe for his research into the importance of biological rhythms and sleep and how they affect people’s lives. His work has been featured in the BBC World Service, the Washington Post, Reuters and other scientific journals and news outlets.
In addition to being a science writer and sleep consultant, Greg also is an entrepreneur who co-founded Resilient Nutrition in 2020, a company that leverages science to produce foods and supplements geared toward helping people feel and perform better. Greg earned undergraduate and master’s degrees in exercise science from Loughborough University in England a Ph.D. from the University of Leeds.
Show notes:[00:03:12] Ken opens part two of our interview with Greg by asking him about continuous positive airway pressure machines, known as CPAPs, that are used for sleep apnea and related disorders, and how these devices relate to circadian rhythms and quality of sleep. [00:05:47] Ken brings up chronotypes, the concept that some people are better suited to an earlier or later sleep schedule. Ken goes on to say that during our interview with Satchin Panda, he argued that chronotypes are largely a myth. Ken asks Greg how much he thinks chronotypes are the product of environment as opposed to evolutionary biology and genetics. [00:10:27] Ken asks what an example would be of an advanced chronotype. [00:11:54] Ken asks Greg about chrononutrition, which is the relationship between a person’s nutrition and their body clock. [00:20:46] Ken mentions that muscle protein synthesis comes up as a problem for people getting older who begin a fasting diet which is generally good for their health but prevents them from maintaining or gaining substantial muscle mass, as their protein demands are higher than they were in youth. Ken asks Greg his thoughts on a pulsatile approach to fasting and protein intake for this cohort. [00:23:39] Ken asks Greg about chronopharmacology, what it is and how it might tie into nutrition. [00:25:21] Ken asks Greg to explain his stance that we should re-engineer our lifestyles to better mimic certain aspects of our distant ancestors to protect ourselves from chronic diseases and revive the kinds of energy we had as children. Greg explains what aspects of our ancient ancestors we ought to emulate. [00:29:07] Ken mentions a paper Greg published on sleep and bodyweight, and asks Greg to expound on the relationship between sleep and weight regulation. [00:33:54] Ken asks if Greg thinks it is true that there is now an “epidemic” of sleep loss. [00:36:57] Greg gives a list of advice for people to optimize their sleep. [00:40:57] Ken mentions that many people enjoy a little wine or other drink before bed because they feel as if it helps them fall asleep. Ken asks Greg to talk about how this can damage a person’s sleep. [00:43:52] Ken asks when people should go to bed, and how much sleep is needed for a person on average, and how much variation there is in the quantity of sleep needed between people. [00:49:12] Ken asks Greg what people should consider when selecting sleep supplements. [00:52:39] Ken mentions that during the COVID-19 pandemic, Greg ventured into the world of entrepreneurship and launched a new company, Resilient Nutrition. Ken goes on to say that Greg has recently launched a new product called Switch On, which Greg has called the first supplement specifically formulated to mitigate some of the negative effects of lost sleep. Ken asks Greg to talk more about this. [00:57:45] Greg talks about the importance of unwinding at the end of the day and some strategies to aid in that, as well as the importance of having a healthy attitude towards sleep. [01:01:14] Ken ends the interview asking Greg if sexual activity prior to sleep influences the quality as well as the duration of sleep.
Episode 136: Greg Potter talks about circadian biology and the importance of sleep
Today we have part one of a two-part interview with Dr. Greg Potter, a British researcher who specializes in circadian biology, sleep, diet, and metabolism. Greg gained attention in the U.S. and Europe for his research into the importance of biological rhythms and sleep and how they affect people’s lives. His work has been featured in the BBC World Service, the Washington Post, Reuters and other scientific journals and news outlets.
In addition to being a science writer and sleep consultant, Greg also is an entrepreneur who co-founded Resilient Nutrition in 2020, a company that leverages science to produce foods and supplements geared toward helping people feel and perform better. Greg earned undergraduate and master’s degrees in exercise science from Loughborough University in England before heading off to the University of Leeds for his Ph.D.
Ken Ford’s STEM-Talk co-host Dawn Kernagis is traveling and was not able to join him for today’s interview with Greg. In this first part of the interview, Ken talks to Greg about his youth and academic background and how he became interested in circadian biology. Greg also goes into detail about why he decided to specialize in sleep and what his research has taught him about the role and importance of melatonin, a hormone that helps control the body’s sleep cycle. Be on the lookout for part two of Ken’s interview with Greg, which covers a number of topics ranging from insomnia, sleep apnea, time-restricted eating, exercise, and nutrition.
Show notes:[00:05:03] Ken opens the interview asking if it’s true that Greg’s curiosity and fascination with building things as a child led him to tell his uncle he wanted to be an engineer when he grew up. [00:06:22] Greg talks about how he and his older siblings lived on the campus of the school where their parents taught. [00:07:35] Ken asks Greg why he abandoned the idea of being an engineer and instead applied for an art scholarship to senior school. [00:08:28] Ken asks what kind of art Greg liked to make. [00:09:17} Ken asks how a rugby injury in Greg’s childhood sparked his initial interest in science. [00:10:33] Ken asks why Greg took a year off before attending university, and what he did during that time. [00:11:04] Greg talks about his first experience with research, which came during a physiological society studentship in his second year of university, where he worked under Dr. Johnathan Folland. [00:12:59] Ken asks about Greg’s experiences as an undergrad when he coached sprinters and worked as a personal trainer and massage therapist. [00:14:18] Ken mentions that Greg must have been a good coach because in addition to training sprinters, he also helped two men break the Atlantic Rowing World Record. [00:16:01] Ken mentions that Greg finished his undergraduate degree in exercise science at Loughborough around the same time as the 2012 London Olympic games. The Great Britain Olympic Team used Loughborough as its base. Greg talks about what a great experience that was for him as a recent graduate who had an interest in elite athletic performance. [00:16:42] Ken asks about Greg’s experience in between his undergraduate and graduate studies, where he took an internship in the sports science and sports medicine department of the Rugby Football Union. [00:17:36] Ken mentions that while at Loughborough pursing a master’s degree, Greg began to pay more attention to the role of biological rhythms and sleep in people’s lives. That prompted him to pursue a Ph.D. at the University of Leeds, researching circadian rhythms, sleep, nutrition, and metabolism. Ken asks why Greg developed an interest in these research topics and what led him to the University of Leeds. [00:19:58] Ken mentions that Greg has become best-known for his work on sleep, asking about a paper Greg published in Endocrine Reviews in 2016 on circadian rhythm and sleep disruption. Ken goes on to ask Greg to explain how circadian rhythms are generated by biological “clocks” and why it is disruptive to good health if we disrupt these rhythms. [00:28:36] Ken asks about the distinction between the body’s master clock and peripheral clocks, and what are some examples of these peripheral clocks and the roles they supposedly play. [00:32:15] Ken mentions that Greg has spoken about how humans once lived by two clocks, a biological one and an environmental one. Ken goes on to explain that these clocks were likely in sync for our ancestors, but that today people seem to have a third clock, which Greg has referred to as a social clock. Greg explains what this social clock is and why it has such a profound impact on humans. [00:37:03] Ken asks about the effects of shift work on people’s circadian rhythms, mentioning a paper Greg co-authored with Tommy Wood, a frequent guest on STEM-Talk. Ken also points out that Satchin Panda (STEM-Talk episode 79) has produced research on shift work. [00:40:04] Ken asks Greg what the current best practices are to optimize health and performance for those who can’t avoid shift work. [00:46:24] Ken mentions that some of the issues around shift work have to do with melatonin. Ken asks Greg to talk about the role and importance of melatonin as well as his thoughts on supplementing it. [00:52:36] Ken mentions that ConsumerLab reported that some over the over-the-counter melatonin they tested was not dosed appropriately. Greg talks about the different pharmacokinetics of melatonin, such as timed release, and under what circumstances which pharmacokinetics are more appropriate. [00:56:11] Ken ends part one of the interview asking Greg to talk about REM sleep disorder and what advice he has for people who suffer from the disorder.
Episode 135: Elaine Lee discusses human performance, resilience and healthspan
Our guest today is Dr. Elaine Choung-Hee Lee, an assistant professor in the Department of Kinesiology at the University of Connecticut. Much of Elaine’s research focuses on understanding the mechanisms of resilience and investigating ways to help humans improve their stress resistance, adaptation and healthspan.
Elaine’s research is focused not only on understanding fundamental biology, but also on what can be done to manipulate our biology to optimize health and performance as well as preventing disease.
At her UConn research center, called the EC Lee Laboratory, she and her colleagues use genomic and other technologies to ask questions about what makes high-performing athletes and warfighters so elite.
In today’s interview, you’ll hear how an early passion for Marvel comics and superheroes helped nudge Elaine into a science career. You’ll also learn about some of her lab’s projects that range from improving warfighter resilience to studying the effects of exercise and supplementation on our immune functions.
Show notes:[00:03:07] Dawn asks Elaine about when she became interested in superheroes. [00:04:02] Elaine shares who her favorite Marvel hero is. [00:05:20] Dawn asks Elaine what her favorite Marvel movie is. [00:05:42] Ken asks when Elaine first became interested in science. [00:06:50] Dawn mentions that Elaine had many obsessions growing up, including running and rowing, and goes on to mention that Elaine even became a rower at the University of Connecticut, asking what drew her to these sports. [00:09:09] Ken asks what Elaine’s experience on the rowing team was like. [00:11:43] Dawn mentions that Elaine graduated with her bachelors in nutritional sciences in 2002 and asks if that was her original intent when she first arrived at college. [00:13:38] Dawn asks Elaine to talk about her passion for research and how the focus of her work grew from her experiences as an athlete and coach. [00:16:14] Dawn comments that Elaine’s early experiences in genetics and nutritional sciences played a role in her career and asks what some of those early experiences were. [00:17:49] Dawn asks Elaine if it’s fair to say that she is not merely interested in biology, but in what people and researchers can do to manipulate biology in a way that can result in functional changes for broader populations. [00:19:13] Ken mentions that Elaine stayed at the University of Connecticut for her masters and doctorate degrees in kinesiology, asking why decided on that specialization. [00:21:34] Dawn mentions that Elaine went for a post-doc fellowship at the Mount Desert Island Biological Laboratory in Salisbury Cove, Maine, and asks how that opportunity came about. [00:23:59] Dawn mentions that during Elaine’s post-doc, she and Dr. Kevin Strange co-authored a paper in the journal of Federation of American Societies for Experimental Biology, titled “Osmosensitive gene expression in C elegans is regulated by conserved signaling mechanisms that control protein translation initiation.” Dawn goes on to mention that this paper was selected in 2012 by the Cellular and Molecular Physiology Section of the American Physiological Society as one of six finalists for its annual research recognition award. Dawn asks why this paper attracted such attention. [00:28:56] Ken mentions that Elaine was also selected as the Mount Desert Island Biological Laboratory’s “Outstanding Mentor of the Year” in 2012. [00:32:18] Dawn mentions that Elaine’s research over the years has focused on understanding the mechanisms of stress resiliency, and ways to improve stress resistance, adaptation and healthspan, asking how Elaine became interested in this angle of research. [00:34:00] Dawn asks Elaine to talk about her use of C elegans and why they are so useful for her research into stress and resilience. [00:38:21] Dawn mentions that Elaine’s work on the mechanisms of osmosensing and adaptation in response to osmotic stress and infection, asking her to give a brief explanation on what osmosensing is. [00:40:45] Ken asks how well the work in C elegans translates to human athletes. [00:43:33] Dawn asks about a study that looked at intracellular and surface heat shock protein 70 expression, as well as early apoptosis and heat tolerance of lymphocytes during 11 days of whole-body heat acclimation. [00:48:15] Dawn asks about a paper that Elaine and Ken Strange wrote in 2012 in the American Journal of Physiology-Cell Physiology which that demonstrated for the first time that inhibition of protein translation protects extant proteins from damage brought about by an environmental stressor, and further asks how this paper challenged some widely held views about chemical chaperones. [00:50:16] Ken asks about a paper Elaine worked on with Jeff Volek and Stephen Phinney, that looked at the metabolic characteristics of keto-adapted ultra-endurance runners. [00:54:22] Ken mentions that last year, Elaine was one of the lead authors of a study that looked at how endocrine response to strenuous experience in the heat can serve as an indicator of the amount of strain experienced by the person. Elaine talks about the findings and significance of this study. [00:56:01] Dawn asks about Elaine’s lab at UConn, called the EC Lee Laboratory, where Elaine and her colleagues study the physiology and genetics of resilience. Elaine talks about how her lab uses genomic technologies to determine what make an elite athlete. [00:58:43] Elaine talks about her lab’s project looking at Aronia fruit in stress resilience and longevity. [01:02:20] Ken asks what the findings have been for human performance in the heat with respect to the Aronia fruit supplement study. [01:03:12] Dawn asks about Elaine’s project focused on enhancing warfighter resilience. [01:06:13] Dawn asks about Elaine’s research on exercise and supplementation interventions on immune function. [01:08:54] Dawn asks about Elaine’s research on transfer RNA (tRNA) and aminoacyl tRNA synthetases relate to the switches that regulate the genes that are important in protecting cells during stress and aging. [01:12:32] Ken notes the disparity in many of the “omics” fields, in that they haven’t delivered many actionable changes in human performance, and asks Elaine to briefly talk about what she thinks might be necessary to bridge this gap. [01:14:22] Ken asks Elaine to briefly explain what network physiology is. [01:15:53] Ken mentions that electrolytes and electrolyte replacement have been a hot topic in sports performance for several years. He asks Elaine what the current ability is to personalize electrolyte replacement, and how does the baseline diet and individual differences in electrolyte loss factor in and are we able to leverage this for better performance. [01:18:44] Dawn asks what advice Elaine gives when people ask her what they can do in terms of exercise, diet, and supplementation to improve their cognitive and physical performance as well as their healthspan. [01:21:35] Dawn asks what Elaine does with her spare time. [01:22:57] To close the interview, Dawn asks Elaine what she finds so rewarding about a career in science.
Episode 134: Mike Griffin discusses America’s hypersonic arms race with Russia and China
Our guest today is Dr. Michael Griffin, the Pentagon’s former Undersecretary of Defense for Research and Engineering. During his two and a half years as undersecretary, Mike made hypersonic weapons and defense against them his number one priority.
In today’s episode, Mike talks about the history of hypersonic technology; why he made it his number one priority at the Department of Defense; and why Russia’s and China’s growing hypersonic capability represents a serious threat to America’s national security.
Our interview with Mike was conducted on March 23, one month following Russia’s invasion of Ukraine. The weekend prior to our interview with Mike, Russia reported that it used a hypersonic missile to strike a Ukrainian military facility.
This is Mike’s second appearance on STEM-Talk. He was our guest on episode 23 back in 2016 when we talked to him about his tenure as NASA Administrator from April of 2005 to January of 2009.
Mike holds numerous academic degrees, including a BS in physics from Johns Hopkins, five master’s degrees, and a Ph.D. in aerospace engineering from the University of Maryland. In addition to serving as NASA Administrator and Undersecretary of Defense for Research and Engineering, his long career has included numerous other academic and corporate positions.
Show notes[00:04:33] Dawn welcomes Mike back to the podcast, mentioning that when Mike was last on STEM-Talk in 2016, he talked about space exploration and his tenure as NASA administrator. Dawn goes on to mention that since then, Mike served a two-and-a-half-year stint as the Pentagon’s first research and engineering undersecretary, a position Congress created in 2018. Mike talks briefly about his perspectives on hypersonics research and development in the U.S. as well as in China and Russia. [00:05:36] Ken asks Mike to give a brief definition of hypersonics, given that during his time as undersecretary, he made hypersonics his top priority. [00:09:59] Ken mentions that last weekend, Russia reportedly used hypersonic weapons in Ukraine. Ken asks if Mike has any thoughts as to why the Russians are using hypersonic weapons in Ukraine as opposed to other less expensive weapons that would have sufficed from a military perspective. Ken wonders whether the use of hypersonics was primarily for strategic messaging. [00:12:26] Ken asks Mike about his op-ed in Breaking Defense that he recently co-authored and was titled, “Rethinking the hypersonic debate for relevancy in the Pacific.” [00:15:17] Ken points out that many U.S. leaders view China as primarily a trading partner and a source of inexpensive goods rather than a power that regards the U.S. as an adversary. [00:16:49] Mike describes hypersonics in more detail and explains the implications for national security. [00:18:28] Dawn mentions that hypersonic technologies are often thought of as relatively new. Mike talks about how the first hypersonic systems were actually used during World War II by the Germans. [00:19:34] Ken explains that the aerodynamic heating that occurs at hypersonic speeds is very intense. As a result, the propulsion technology, airframe materials and thermal management involved in hypersonics is very demanding. Ken goes on to say that in the mid-1950s, this was an issue the Air Force had to overcome during its development of the Atlas Intercontinental Ballistic Missile. Ken asks Mike to discuss aerodynamic heating caused by hypersonic speeds and how it was handled with respect to the Atlas missile. [00:23:12] Ken asks about the challenges NASA faced in overcoming aerodynamic heating on the Command Module for the Apollo missions during reentry, which would reach speeds up to Mach 35. [00:23:49] Dawn explains that hypersonic weapon systems fall primarily into two classifications: air-breathing cruise missiles and hypersonic boost-glide systems. She asks Mike to give an overview of these two systems and asks if as a country we should invest in both. [00:30:01] Ken asks Mike whether a powered cruise missile or a hypersonic boost-glide system is more challenging to develop and deploy. [00:32:44] Ken explains that the United States has actively pursued the development of hypersonic weapons as a part of its conventional global strike program since the early 2000s. Ken adds that partly thanks to Mike’s efforts, the Pentagon and Congress have recently shown a renewed interest in the development and deployment of hypersonic systems, possibly due to the existence of operational Russian and Chinese hypersonic systems. Ken asks Mike when he thinks the U.S. might have operational hypersonic capability and what it might be like. [00:35:00] Ken asks Mike about the balance between developing hypersonic weapons and developing a new type of defense system to counter the Russian and Chinese threat. [00:40:41] Ken follows up by asking if the space development agency is adequately funded and staffed for the task of developing a detection and defense system for hypersonic weapons. [00:42:59] Dawn asks why the United States fell behind in hypersonic technology when in the ‘60s the U.S. was the leader in this field, developing the X-15 aircraft that flew at hypersonic speeds. [00:45:12] Dawn mentions that the bedrock of military thinking since the start of the nuclear age has been the psychology of Mutually Assured Destruction, but that hypersonic missiles compress the time that a military will have to take defensive steps or retaliate. She asks if we are entering an era where the pressure to strike first is greater than ever. [00:49:02] Dawn asks if Mike thinks Washington, Moscow and Beijing might have serious discussions about the development and deployment of hypersonic technology that will eventually lead to treaties being negotiated by the superpowers. [00:53:05] Ken mentions that he recently listened to an interview with Dr. Mark Lewis, a former Air Force Chief Scientist, in which Mark and Dr. Dick Hallion remarked that the Russians and Chinese are indeed ahead of us in hypersonic technology. They pointed out China’s and Russia’s advantage is at least partly because they benefited substantially from the research, reports and papers that were produced by NASA and the Air Force. Ken asks if this view matches Mikes own observations. [00:55:30] Ken asks if there are any other nations, aside from Russia and China, with active hypersonics development programs. [00:56:56] Ken asks if Mike thinks our universities are producing the engineering brainpower we need to compete with the Chinese and Russians. [00:59:24] Dawn shifts to talk about NASA’s Perseverance Rover, which landed on Mars a year ago. She asks if Mike Agrees with NASA’s description of the landing as a pivotal moment for the United States and space exploration. [01:02:17] Ken mentions that Mike has long been an advocate for the human exploration of Mars. Ken also points out that Mike’s proposed strategy is to begin by returning to the Moon, which NASA is planning to do with the upcoming Artemis mission. NASA’s goal is to build a long-term human presence on the Moon. Ken asks Mike to discuss the strategy for the Artemis mission. [01:06:12] Dawn asks why Mike believes that returning to the moon and human exploration of Mars should be a national priority. [01:07:17] Dawn asks Mike for his thoughts about the likelihood of the U.S. working together with Russia again on space missions, given the conflict in Ukraine as well as the decision to suspend a joint European-Russian mission to Mars because of Ukraine. [01:09:30] Dawn closes the interview asking about Mike’s new company that he co-founded called LogiQ Inc, which provides high-end management, scientific and consulting services.
Episode 133: Mark Mattson talks about the benefits and science of intermittent fasting
Our guest today is Dr. Mark Mattson, who is affectionally known as the godfather of intermittent fasting. The National Institute of Health describes Mark as “one of the world’s top experts on the potential cognitive and physical health benefits of intermittent fasting.” He is considered a leader in the area of cellular and molecular mechanisms underlying neuronal plasticity and neurodegenerative disorders and has made major contributions to understanding the pathogenesis of Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and stroke, and to their prevention and treatment.
After spending nearly 30 years researching calorie restriction and intermittent fasting, Mark has written a book on the topic, “The Intermittent Fasting Revolution: The Science of Optimizing Health and Enhancing Performance.” Our interview with Mark came the day after MIT Press released his book.
This is the second time Mark has appeared on STEM-Talk. When we interviewed him back in 2016, intermittent fasting didn’t register on Google’s list of top-10 searches related to diet and eating plans. By 2019, however, intermittent fasting was more widely searched on Google than any other diet. Today, intermittent fasting and the ketogenic diet jockey for Google’s top spot for diet searches.
We talk to Mark in this interview about how, as the title of his book suggests, we are indeed in the midst of an intermittent fasting revolution. In today’s episode, Mark walks us through our evolutionary history and how it has sculpted our brains and bodies to function optimally in a fasted state. We talk about ways our overindulgent sedentary lifestyles have negatively impacted not only our waistlines, but also the size of our brains. After describing the various ways to go about intermittent fasting, Mark dives into the science behind fasting. This leads to a fascinating discussion about the metabolic switch that transitions a person from the utilization of glucose to the utilization of fat-derived ketones and how research is showing that this switch becomes an important factor in the treatment of not only cognitive disorders like Alzheimer’s, but also a range of other diseases and disorders like cancer, diabetes, inflammation, kidney, and heart disease.
Mark is on the neuroscience faculty at Johns Hopkins University School of Medicine. He recently retired from the National Institute of Aging where he led its neuroscience laboratory for the past 20 years.
Show notes:[00:04:16] Dawn opens the interview congratulating Mark on his new book and asks how long it took him to write it. [00:05:09] Dawn mentions that when Mark was last on STEM-Tall in 2016, intermittent fasting was just beginning to come to the public’s attention, and that today it is almost impossible to pass a grocery store checkout counter without seeing a rack of magazine covers touting intermittent fasting. Dawn asks Mark for his thoughts about what happened in the past decade to suddenly spark so much public interest in fasting. [00:08:20] Ken mentions the title of Mark’s new book, “The Intermittent Fasting Revolution: The Science of Optimizing Health and Enhancing Performance.” Ken asks Mark to expound on the idea that we are witnessing a revolution of interest in intermittent fasting. [00:10:39] Dawn explains that the first chapter of Mark’s book begins with an overview of how evolution sculpted humans and animals to function best in a fasted state. Mark, in this section of his book, makes the point that fasting is not a diet, but an eating pattern that puts a person into a fat-burning state. Dawn asks Mark to briefly walk through this evolutionary history. [00:13:06] Ken mentions that Yuval Noah Harari, author of, “Sapiens: A Grief History of Human Kind,” has said that ancient foragers were the most knowledgeable and skillful people in history. Ken asks Mark to weigh in on Harari’s point that the size of the average brain in Homo Sapiens has actually decreased since the age of hunters and gatherers. [00:17:10] Dawn asks Mark to talk about how our modern overindulgent sedentary lifestyles are having negative impacts on our brains. [00:18:20] Dawn mentions that fasting was relatively popular in the U.S. at the turn of the 20th Century and mentions Josh Turknett, who was recently on STEM-Talk, pointed out that Upton Sinclair actually wrote a book about fasting in 1911. Dawn mentions that Mark in his book also writes about Sinclair as well as Dr. Edward Dewey, who in 1900 wrote “The No-Breakfast Plan and the Fasting Cure.” Dawn asks why society turned its back on fasting when a century ago it was quite popular. [00:19:55] Ken asks Mark to explain how he first became interested in researching intermittent fasting in the 1990s. [00:22:10] Dawn explains that Alzheimer’s disease ultimately affects almost half of the population over the age of 85, and that diseases such as Alzheimer’s and Parkinson’s often start 15 years before serious symptoms are noticed. Dawn asks Mark to explain the hallmarks of brain aging in relation to these diseases. [00:24:55] Ken asks about the evidence for fasting-induced autophagy in humans, and how much fasting is required to activate it. [00:26:22] Dawn asks about the emotional impact of Alzheimer’s and mentions that Mark’s father was diagnosed with the disease. [00:29:57] Mark expounds on his observations that Alzheimer’s and many other diseases of neural degeneration and cognitive decline are largely metabolic diseases. [00:31:45] Ken asks if the loss of muscle mass could have an impact on Alzheimer’s due to the role skeletal muscle plays in glucose storage. [00:33:11] Ken mentions that Mark writes in his book that fasting is characterized by an increase in the concentration of ketones in the blood, and that fasting therefore can be thought of as a ketogenic diet. Ken goes on to mention that in a relatively sedentary person it typically takes about 12 hours to deplete their liver glucose stores and trigger ketones. Ken asks Mark to walk through the chain of events that happen once glucose in the liver is depleted. [00:34:59] Dawn asks Mark to give a brief description of some of the more popular ways of fasting such as time restricted eating, prolonged fasts, fasting mimicking diets, and the 5:2 fast. [00:37:40] Dawn mentions that Gary Taubes came on STEM-Talk last year to talk about his new book “The Case for Keto: Rethinking Weight Control and the Science and Practice of Low-Carb/High-Fat Eating.” Dawn asks if there are differences in terms of the benefits of intermittent fasting and a low-carb ketogenic diet. [00:39:48] Ken asks Mark what distinguishes fasting from caloric restriction, and why does fasting yield benefits beyond what we see in caloric restriction. [00:42:10] Dawn asks about Mark’s work today at Johns Hopkins. [00:44:50] Dawn mentions that one of the key takeaways from Mark’s new book is that metabolic syndrome can often be completely reversed by the adoption of a lifestyle that includes intermittent fasting and exercise. Mark points out that there are studies of animals and humans, however, that show intermittent fasting alone can reverse metabolic syndrome. Dawn asks if Mark believes that a combination of exercise and intermittent fasting is still the best approach. [00:46:33] Ken asks about Mark’s 2019 study that looked at how intermittent fasting improves mood and cognition, which found that hippocampal neuronal networks adapt to intermittent fasting by enhancing GABAergic tone, which is associated with reduced anxiety and improved hippocampus-dependent memory. [00:49:37] Dawn asks about another of Mark’s studies published in 2019 that highlighted what research has revealed so far about the effects and benefits of intermittent fasting. [00:53:06] Dawn asks Mark to briefly discuss why switching the metabolic switch from glucose to ketones seems to have a near system-wide effect, improving outcomes in diabetes, multiple sclerosis, epilepsy, kidney disease as well as stroke. [00:55:13] Ken mentions that intermittent fasting seems to have benefits for a wide swath of our generally overweight and metabolically unhealthy population but wonders if it might be inappropriate in the long-term for vulnerable populations such as the elderly experiencing sarcopenia. [00:59:45] Dawn explains that cardiovascular disease is the leading cause of death in the U.S. and that the fourth leading cause of death is stroke. She goes on to explain that the combination of obesity, insulin resistance, hypertension and aging are the major risk factors for cardiovascular disease and stroke, but there are now studies that show intermittent fasting can reduce stroke and heart disease. Dawn asks Mark which of these findings he thinks shows the most promise. [01:01:22] Ken asks about the new book Mark is currently working on, which has the working title of “Sculptor and Destroyer: The Story of Glutamate, the Brain’s Most Important Neurotransmitter.” [01:04:39] Ken closes the interview asking when the new book is set to go to the publisher.
Episode 132: Martin Kulldorff discusses vaccines, lockdowns, school closings and the global response to COVID-19
Our guest today describes the global response to COVID-19 as one of the biggest public-health fiascos in history. As you would expect, he gained quite a bit of notoriety for this contrarian view. Dr. Martin Kulldorff is an epidemiologist and biostatistician who has spent the past 30 years researching infectious diseases as well as the efficacy and safety of vaccines.
He is internationally known for his statistical and epidemiological methods for the early detection and monitoring of infectious diseases. A former Harvard Medical School professor who today is the Senior Scientific Officer at the Brownstone Institute, Martin worked with the Centers for Disease Control on its current system for monitoring potential vaccine risks. Today, the U.S. and other countries around the world use Martin’s detection methods to monitor COVID-19.
Martin made national headlines in October of 2020 when he and Dr. Jay Bhattacharya of Stanford and Dr. Sunetra Gupta of Oxford published the Great Barrington Declaration, a paper that questions school closings, lockdowns, travel restrictions and other governmental responses to the COVID-19 pandemic. The three authors recommended “focused protection” instead, a policy of protecting senior citizens and others who are most at risk of dying from COVID while allowing young people and others who face minimal risk of death to resume their normal lives.
The three authors were immediately skewered for what critics called a radically dangerous approach for pandemic management.
At STEM-Talk, however, we appreciate that a curious, open, and even skeptical mind is at the heart of the scientific method. Because of that, we have invited Martin to sit down with us to discuss the Great Barrington Declaration as well as his views about pandemics and the best ways to safeguard the public. We also review with Martin the age-adjusted mortality rates of states like Florida, New York and California which had quite different responses to COVID-19.
Ironically, co-host Dawn Kernagis learned on the morning of our interview with Martin that she had contacted COVID. So, she has to skip today’s discussion. (Note to listeners: It was just a mild case and Dawn is already back on her feet.)
But in today’s fascinating episode, Martin and host Ken Ford discuss:
— The safety of vaccines, including the coronavirus vaccines.
— Martin’s thoughts about the Pfizer BioNTech COVID-19 vaccine for children.
— The Great Barrington Declaration and the concerns it raised about the physical, mental-health and economic impacts of the prevailing COVID-19 responses.
— The effectiveness of natural immunity compared to vaccine-induced immunity.
— Whether hospitals should be hiring caregivers with natural immunity rather than firing them.
— Martin’s thoughts about Sweden, which was the only Western nation that did not impose lockdowns or close its schools and daycare centers in response to COVID-19.
— What age-adjusted COVID mortality rates for the U.S. have to say about the different approaches states used in response to the pandemic.
Show notes:[00:05:20] Ken opens the interview mentioning that Martin was born in Lund in 1962 in southern Sweden, but grew up in Umea, a university town in northeast Sweden. Ken asks what prompted Martin’s family to move to Umea when he was two years old. [00:05:47] Ken mentions as an aside that he once spent an enjoyable week at the University of Umea visiting Lars-Erick Janlert. Ken served as the external expert for a PhD dissertation. [00:07:00] Ken asks Martin what he was like as a child. [00:07:32] Ken asks what drew Martin to math, and if it came naturally to him. [00:08:15] Martin talks about his decision to attend Umea University and major in mathematical statistics. [00:09:09] Ken asks why Martin moved to the United States and to attend Cornell University as a Fullbright Fellow for his postgraduate studies, and why he decided to earn his Ph.D. in operations research. [00:10:39] Ken asks about the software Martin developed called SaTScan, which analyses spatial, temporal, and space-time data for the purposes of geographical and hospital-disease surveillance. [00:14:13] Ken asks why Martin returned to Sweden to be an assistant professor in statistics at Uppsala University after receiving his Ph.D. [00:15:26] Ken asks when and why Martin became primarily focused on diseases and epidemiology rather than other fields where statistics is applicable. [00:16:47] Ken mentions TreeScan, a data mining software package that Martin developed which looks for excess risk in a large number of individual cells in a database as well as in groups of closely related cells. Ken asks Martin to talk about how this software is used for disease surveillance and what some of its key features are. [00:18:09] Ken mentions that Martin is also the co-developer of the R-Sequential software program used for exact sequential analysis, with his key scientific contribution to it being the development of the statistical and epidemiological methods used in this software. Martin gives an overview of what these methods include. [00:20:01] Ken asks why Martin returned to a university setting when he left the National Cancer Institute to work at the University of Connecticut. [00:20:50] Ken mentions that in 2002, Martin took a position as a professor of medicine at Harvard Medical School and Brigham Women’s Hospital. Martin talks about how much of his research at the time was focused on developing new statistical and epidemiological methods for disease surveillance and looking at ways to optimize health outcomes for individuals and populations. [00:21:43] Ken asks Martin to talk about his work with a CDC working group that looked at the Measles-Mumps-Rubella Vaccine, also known as the MMR vaccine. [00:25:34] Ken mentions that Martin had been a member of the FDA’s Drug Safety and Risk Management Advisory Committee and asks Martin to talk about this work. [00:28:06] Ken asks about Martin’s work as part of the World Health Organization’s Disease Mapping Advisory Group in 1997. [00:29:07] Ken asks Martin to describe how his methods and contributions to the development of statistical and epidemiological methods for early identification of infectious disease outbreaks are being used today to monitor COVID-19 in the U.S. and abroad. [00:30:18] Ken mentions that much of Martin’s research today focuses on developing and applying new disease surveillance methods for post-market drug and vaccine safety surveillance. Ken also mentions that a significant number of people today have concerns about the safety of not just the coronavirus vaccines, but all vaccines. Ken asks what insights Martin can share with people about the safety of the coronavirus vaccines as well as vaccines more generally. [00:32:57] Ken mentions that Martin has helped develop key parts of the U.S. vaccine safety system, and in 2020 he became a member of the CDC’s Covid Vaccine Safety Technical Work Group which reviewed COVID-19 vaccine safety data on a weekly basis when the U.S. began its vaccination program. Ken goes on to mention that in April of 2021, the CDC removed Martin from the work group after he publicly disagreed with the agency’s pause of the Johnson and Johnson COVID vaccine for older Americans. Ken asks Martin what his key objections were to the pause of the J&J vaccine and what were the issues that led to his removal from the safety group. [00:38:32] Ken explains that the CDC is now recommending the Pfizer BioNTech COVID-19 vaccine for children 5 through 11 years old, as well as children 12 to 17. Ken asks what Martin’s thoughts are on this and what advice does he have for parents about giving this to their children. [00:41:59] Ken explains that Martin has been an outspoken critic of not only the U.S. response to COVID-19, but also the global response, which he has described as the biggest public health fiasco in history. Ken goes on to mention that Martin and two other scientists – Sunetra Gupta fron Oxford and Jay Ghattacharya of Stanford – wrote The Great Barrington Declaration, which raised concerns about the damaging physical, mental-health, and economic impacts of the prevailing COVID-19 responses. Instead of Lockdowns, Martin and his colleagues recommended focused protection. Ken asks why Martin thinks lockdown policies have produced devastating effects on short and long-term public health. [00:44:53] Martin elaborates on the concept of focused protection and how it is fundamentally different than the lockdown approach. [00:49:00] Ken mentions that Martin has made the point that nurses and caregivers who have recovered from COVID-19 have stronger and longer-lasting immunity than vaccinated people who have not been infected with COVID-19. Ken asks Martin to elaborate on his position that hospitals should be hiring caregivers with natural immunity rather than firing them if they refuse to take the vaccine. [00:51:47] Ken mentions that a recent Israeli study conducted in early 2021, that looked at a group of people who had contracted coronavirus and thus had natural immunity. The study demonstrated that natural immunity confers longer lasting and stronger protection against infection, symptomatic disease, and hospitalization than two-dose vaccine-induced immunity. Ken mentions that this study has not been peer-reviewed yet and it only focused on Israelis who received the Pfizer vaccine, but asks Martin to give his initial thoughts about what this research shows in terms of an immune hierarchy related to the coronavirus. [00:54:23] Ken asks if we know if there is a difference of degree of protection afforded to individuals infected by different variants of COVID-19. [00:55:54] Ken mentions the John Snow Memorandum, published in in The Lancet, which is a response by 80 researchers denouncing the Great Barrington Declaration. Ken explains that the memorandum contends that the idea of herd immunity is a “dangerous fallacy unsupported by the scientific evidence.” [00:58:49] Ken mentions that Martin has been a proponent of the approach that has been followed by Sweden, which was the only Western country that did not close its schools or daycare centers, asking Martin to talk about Sweden’s response and some of the key lessons and insights that we should take away from it. [01:03:37] Ken explains that Martin and his co-authors of the Great Barrington Declaration have been fiercely criticized, with William Haseltine, a former Harvard Medical School professor saying herd immunity was just another word for mass murder. Ken goes on to explain that Haseltine, in 2020, said that if we allowed the virus to spread in an attempt to reach herd immunity, that we were looking at two to six million American deaths. Ken goes on to say that this has not happened either in the U.S. or in Sweden, and asks Martin if he thinks there is more openness today in the research community to the points raised in the Great Barrington Declaration, as well as Sweden’s response to COVID-19. [01:08:57] Ken mentions that lockdown policies affect working class people the most, those who cannot perform their work over Zoom. It affects people like policy makers the least. Ken and Martin discuss how different the pandemic has been for the Zoom class compared to the working class. [01:11:43] Ken explains that New York State and California both had long periods of strict lockdowns in 2020 and 2021 while Florida had a shorter lockdown period and reopened businesses and tourism and schools much sooner than most states. Ken goes on to mention that Florida has also rejected mask and vaccine mandates and that a lot of people have second-guessed Florida’s approach to COVID. But in terms of age-adjusted COVID mortality rates, Florida is much like Sweden in that the catastrophe that was supposed to happen didn’t. Ken explains that New York had one of the highest age-adjusted COVID mortality rates while Florida and California had mortality rates lower than the national average. Ken asks Martin for his take on Florida and California’s identical outcomes although the two states had starkly contrasted responses to the virus. [01:14:56] Ken asks about the increase in hospitalizations among children with the Omicron variant. [01:18:20] Ken asks if Martin thinks we should start to accept that we can’t eliminate COVID and its variants, much like the flu, and instead should work towards mitigating risks in the future. [01:24:06] Ken mentions that Martin recently left Harvard and has joined the Brownstone Institute as its Senior Scientific Director. Ken explains that Brownstone was founded in 2021 to respond to the COVID crisis and provide a “safe haven” for scientific research. When accepting his new role, Martin said that “governments, universities and scientific leaders have failed us during this pandemic, resulting in the biggest health fiasco in history.” Ken asks what Martin hopes to accomplish through his work with Brownstone. [01:27:10] Ken talks about how non-medical experts like engineers, computer scientists and mathematicians are increasingly analyzing medical research and producing sophisticated observations that are at times at odds with medical orthodoxy. Ken asks Martin if he believes this kind of research by so-called outsiders should be encouraged or, like some suggest, should be censured. [01:31:02] As Ken closes the interview asking Martin if it is true that something besides COVID also weighs heavily on Martin’s mind.
Episode 131: Christopher Logothetis discusses advances in prostate cancer therapies
Our guest today is Dr. Christopher Logothetis, one of the nation’s foremost experts on prostate cancer. Chris has spent nearly five decades at MD Anderson in Houston developing therapies for prostate cancer as well as conducting research into the underlying biology of the disease.
Aside from skin cancers, prostate cancer is the most common cancer among men, claiming a man’s life every 15 minutes in the United States, according to the Prostrate Cancer Foundation. Since the 1970s when Chris joined the staff at MD Andersen, which is the nation’s top-ranked hospital for cancer care, he has been dedicated to the treatment, research, and prevention of genitourinary cancers such bladder, kidney, testes and penis cancer. For the past 25 years, he has focused primarily on prostate cancer and the development of effective chemotherapy treatments.
Today, Chris is the director of MD Anderson’s Genitourinary Cancer Center and the director of the Prostate Cancer Research Program.
Show notes:[00:03:23] Dawn opens the interview mentioning that Chris went to medical school in Greece and asks if he grew up there as well. [00:03:43] Ken asks Chris when he first became interested in science. [00:04:09] Dawn asks if there were a particular teacher or class that prompted Chris’ decision to pursue medicine. [00:04:39] Dawn asks what led Chris to attend the University of Athens School of Medicine. [00:05:10] Dawn mentions that in the ‘60s and ‘70s, talking about cancer was almost taboo and asks Chris to talk about the stigma that surrounded cancer for quite some time. [00:05:57] Ken asks if Chris knew he wanted to specialize in cancers when he first started medical school in Athens or if that interest developed later. [00:07:06] Dawn mentions that Chris graduated from medical school in 1974 and then took off for Chicago where he had an internship at Cook County Hospital. Dawn asks about the experience, and if it were a culture shock to go from Athens, Greece to Chicago in the 1970s. [00:08:54] Dawn asks what took Chris to Texas and MD Anderson after his time in Chicago. [00:09:36] Dawn mentions that after Chris finished his fellowship, he joined the faculty at MD Anderson, and is now coming upon his 50th anniversary there. [00:09:51] Chris explains his view that we need to better understand the drivers of cancer and goes on to talk about what we currently know about these drivers. [00:12:06] Ken asks about the significance of the Human Genome Project on cancer research. [00:13:49] Dawn mentions that along with new technologies, there evolved a strategy of what is called co-clinical investigation where researchers study the mouse, but in parallel look at the difference and similarities with humans. She asks him about how that integrated data required a new language to bring it all together, which is now known as Prometheus. Dawn asks Chris to talk about Prometheus and how this has led to an accelerated understanding of cancer biology. [00:20:47] Dawn mentions that Chris has studied a range of genitourinary cancers throughout his career, such as germ cell tumors, bladder, and renal cancers, but that his interest in prostate cancer is a more recent development. Dawn asks what led to this specific interest. [00:23:12] Dawn explains that metastatic cancer was first cured in 1956 when methotrexate was used to treat a rare tumor called choriocarcinoma. She goes on to say that since then, chemotherapy drugs have been used to treat mixed germ-cell tumors and has led to dramatically improved survivorship among patients with metastatic germ-cell tumors. She also mentions that in 1982 Chris published a paper in the journal Cancer titled, “The growing teratoma syndrome,” at which time, tumor growth following chemotherapy for mixed germ-cell tumors had been considered a reliable indicator of a persistent active carcinoma, with the rule being that if the cancer didn’t respond to treatment that operations were futile. Dawn explains that in Chris’ 1982 paper, he demonstrated that you could alter a tumor with chemotherapy in such a way that surgery could now cure it where previously could not. Chris expounds on this paper and its significance. [00:27:21] Ken mentions that Chris had another paper where he described the spiral diagram of cancer progression, where the cancer sends a message to the host, which sends a message back in a cycle over time. Ken goes on to say that Chris’ conclusion was that this interaction between the cancer and the host eventually evolves into the patient’s body and becomes, in a sense, complicit in the cancer’s growth. Chris goes on to explain the spiral of cancer progression. [00:31:19] Dawn points out that in the spring of 2021, Chris published a paper in Clinical Cancer Researched titled “Radium-223 Treatment Increases Immune Checkpoint Expression in Extracellular Vesicles From the Metastatic Prostate Cancer Bone Microenvironment.”Dawn goes on to explain that Radium-223 is a radiopharmaceutical used to treat metastatic cancers in bone. Bone-targeting radiotherapy with Radium-223 prolongs the survival of patients with metastatic prostate cancer. Treatment, however, is often followed by a detrimental relapse and progression. Dawn explains that despite this, Chris detailed in his aforementioned paper a treatment strategy that could potentially increase the effectiveness of Radium-223. [00:34:24] Ken mentions that prostate-specific antigen test, or PSA, has become controversial for its utility as a screen, and asks Chris for his thoughts on the matter. [00:36:09] Ken asks if a change in PSA levels in a patient over time is more of an elucidating marker than a single high value at one point in time. [00:38:20] Dawn mentions that Chris wrote in a paper that appeared in the Journal of Cell Science & Therapy. “When we aspire to cure cancer, we need to search no further than a curable cancer such as germ cell tumor of the testis, also known as TGCT.” Dawn asks Chris to expound on this paper and how TGCT provides us invaluable lessons about curing other intractable solid tumors. [00:41:18] Ken mentions that Chris and his colleagues at MD Anderson and the School of Medicine at the University of Thessaly in Greece wrote an opinion piece that ran in European Urology titled “Prostrate Cancer: Quo Vadis?” The article stressed that utility measures are urgently needed for the clinical application of new diagnostics to reduce excessive intervention. Ken asks Chris to provide more background on this piece and describe the type of diagnostics he and his colleagues recommend in it. [00:44:27] Dawn explains that while there has been some very promising research into the development of a stress response therapy, metastatic prostate cancer remains an incurable disease, and no effective therapies have yet come out of the research. She goes on to say that Chris addressed this issue in a 2018 article in Science Translational Medicine titled “ER stress in prostate cancer: A therapeutically exploitable vulnerability?” The article was in response to a paper that also appeared in Science Translational Medicine titled “Development of a stress response therapy targeting aggressive prostate cancer.” Dawn asks why Chris wrote this response, and since the publishing of these papers, if there has been much progress in developing effective therapies that target these aggressive prostate cancers. [00:49:12] Dawn mentions that prostate cancer is a highly heritable disease with disparities in incidence rate across ancestry populations, with the Prostate Cancer Foundation saying that this is one of the largest health disparities in all of medicine. Dawn asks Chris what his thoughts are on this in light of his investigations into the issue. [00:51:29] Ken explains that there is a precision prostate cancer screening in development called the “Smith Test,” which is something that could help address the disparities in incidence rates across ancestry populations. He goes on to say that the test is described as a simple blood test, similar to a cholesterol test, that would be able to indicate the lifetime risk of prostate cancer of any man. Chris gives his thoughts on this effort. [00:55:35] Since the death rate from prostate cancer dropped more than 50 percent since the establishment of the Prostrate Cancer Foundation in 1993, Dawn asks Chris about research on the horizon that gives Chris the most hope. [00:58:27] Dawn mentions Chris’ evening lecture at IHMC titled “Addressing Paradoxes in Health Care,” and asks Chris to give a short summary of his talk. [01:02:25] Dawn asks if Chris is currently considering retirement anytime soon. [01:04:16] Ken asks about Chris’ passion for sailing. [01:06:40] Dawn closes the interview asking if it is true that Chris is such an avid sailor that he has a sailboat in Greece as well as Texas, and that he does some of his best work on sailboats.
Episode 130: Josh Turknett talks about holistic approaches that help people end chronic migraines
Our guest today is Dr. Josh Turknett, the author of “The Migraine Miracle” and “Keto for Migraine,” two books that have helped thousands of people use a holistic approach to end their chronic migraines. Josh is often referred to as “public enemy number one to migraines” everywhere.
He is a neurologist, musician, author, and entrepreneur. He has more than two decades of experience in the field of cognitive and behavioral neuroscience. Josh practices medicine in Atlanta at the Turknett Center for Neurology and Cognitive Enhancement.
In today’s episode, we talk to Josh about his own history with migraines and how migraine is a common and complex neurological disorder that includes a genetic component.
Josh earned a bachelor’s degree in cognitive neuroscience from Wesleyan University, an M.D. from Emory University, and completed his residency training at the University of Florida.
In addition to his medical practice, Josh also is the founder of Brainjo, a company that creates educational resources that utilize a system of instruction based on the science of learning and neuroplasticity. He’s a musician who plays in the band The Georgia Jays and teaches people to play the clawhammer banjo, fingerstyle banjo, fiddle and ukulele. As if he didn’t have enough to do, Josh also is the president of Physicians for Ancestral Health and the chief medical officer for humanOS, which was recently acquired by Restore Hyper Wellness. Josh also is the host of the Intelligence Unshackled podcast, which explores the many ways that human potential is constrained and how people can go about optimizing it.
Show notes:[00:03:22] Dawn opens the interview asking Josh about his mother’s struggles with migraines. [00:04:59] Dawn asks Josh how old he was when he first started having migraines. [00:06:15] Ken asks Josh how he first became interested in science. [00:08:24] Dawn asks Josh how he ended up in the Connecticut at Wesleyan University for his undergraduate degree. [00:09:35] Ken asks if Josh knew he wanted to major in neuroscience when he first arrived at Wesleyan or if that was a later decision. [00:10:49] Dawn asks if it is true that Josh’s girlfriend at the time played a role in his decision to move back to Atlanta to go to medical school at Emory after his undergrad. [00:11:55] Dawn asks what motivated Josh to attend the University of Florida for his residency after being a lifelong Gator-hater. [00:14:39] Ken mentions that despite all the hype around neuroscience when the field was emerging, the last major breakthrough in neurology was in the ‘90s with the discovery of triptan drugs for migraines. Ken asks if we have made any major neurological advances since then, and if not, why? [00:17:41] Ken asks Josh what he would suggest to today’s neurology residents and neuroscience graduate students who might want to avoid the recent failures of the modern approaches to treating neurological disease. [00:19:57] Dawn explains that a migraine is a complex neurological disorder affecting 15 to 20 percent of the population, with many subtypes including a genetic component. Dawn asks Josh what is currently understood about the genetic component of migraines. [00:21:28] Ken asks Josh at what point in his career did he decide to specialize in migraines. [00:23:17] Dawn asks Josh to explain to people who have not suffered from migraines what it feels like to experience a cascade of symptoms such as numbness, tingling, visual disturbances, nausea, vomiting, dizziness, fatigue, and blinding headaches. [00:25:15] Ken asks Josh what the difference is between cluster headaches and migraines. [00:26:49] Dawn mentions that people can start to feel the onset of a migraine 48 hours before the pain sets in, a phase called the prodrome. Josh explains what the prodrome is and what its symptoms are. [00:28:03] Dawn mentions the fact that the pain of a migraine is preceded by an aura, which is often a frightening but temporary neurological disturbance that sets off an alarm of an impending migraine headache. She asks Josh what is known about auras. [00:30:11] Ken asks if the auras experienced by migraine sufferers is similar to the experiences some people have preceding an epileptic seizure. [00:30:41] Ken asks if people bounce back immediately once the migraine is over, or if there is a recovery period involved. [00:31:53] Dawn switches to the topic of how diet and lifestyle can help people manage their migraines by asking Josh about how his interest in ancestral health, and the ancestral way of eating. [00:34:43] Ken asks Josh what discoveries led him to write his 2013 book, “The Migraine Miracle.” [00:38:12] Dawn mentions that the ketogenic diet has become extremely popular over the past few years. Dawn goes on to say that while the ketogenic diet has been largely understood to help people with weight loss, epileptic seizures, metabolic disorders, and many other health issues. Dawn asks Josh to talk about how when his book “Keto for Migraine” came out, there weren’t many references to how a low-carb/high-fat diet could help people with their migraines. [00:42:16] Dawn mentions that in “Keto for Migraine” Josh points out that the typical version of the ketogenic diet can make migraines worse. Given that, Dawn asks what the keys are for maximizing the benefits of keto for the migraine brain. [00:43:12] Dawn asks Josh to address how ketosis impacts blood cholesterol testing. [00:45:46] Ken asks what other things Josh has learned about ketosis and the migraine brain. [00:48:42] Ken mentions fasting as a way to induce ketosis, and asks if Josh utilizes fasting, either for himself or as a recommendation for his patients. [00:51:43] Although fasting has become a popular fad in recent years, the journalist Upton Sinclair wrote a best-selling book back in 1911 called “The Fasting Cure.” Dawn asks Josh about the interesting things he learned from reading Sinclair’s book. [00:53:34] Ken asks if Josh has investigated the possibility of a connection between migraines and gut health, given the multitude of disorders now being associated with a breakdown in the gut. [00:56:25] Dawn mentions that in addition to Josh’s medical practice, he is a musician, playing banjo for the Georgia Jays. He also is an entrepreneur, a business consultant, and is currently the president of the Physicians for Ancestral Health, a role previously held by Tommy Wood. Dawn asks how Josh can manage this wide variety of roles and interests. [00:58:49] Dawn asks how long Josh has been playing banjo. Josh also talks about the band he plays with, the Georgia Jays. [01:00:08] Dawn mentions Josh’s book “The Laws of Brainjo,” a compilation of articles about the fundamental principles of learning, described by Josh as a neuroscience-based system of instruction for learning as well as an owner’s manual for molding a musical mind at any age. Josh gives a brief overview of his Brainjo system. [01:03:33] Ken mentions Josh’s recent IHMC lecture about how the significant reduction in cognitively demanding activities that occurs over a typical human lifespan may be a driving force in the development of cognitive decline and dementia, a phenomenon described as the Demand Driven Decline Theory. Ken asks Josh to touch on the Demand Driven Decline Theory and on some of the key points from his lecture. [01:08:04] Dawn mentions that a previous STEM-Talk guest, Dr. Dale Bredesen has proposed a multi-modal model that includes toxic exposures, stressors, diet, genetics, and hormonal effects as drivers of cognitive decline that need to be individually assessed and addressed based on the patient. Dawn goes on to explain that in this model, the capacity of the brain slowly decreases over time as injury accumulates, until supply of cognitive function no longer meets demand. This model contrasts Josh’s Demand Driven Decline Theory and given that there is evidence to support both theories, Dawn asks Josh how they might be reconciled. [01:11:15] Ken asks Josh to reiterate the importance of adults doing things they are not good at, and if Josh has any thoughts on how we can encourage and support people to continue to learn new skills. [01:15:09] Dawn mentions that in 2018, Josh launched the Intelligence Unshackled podcast, which explores the potential of human intelligence. Dawn goes on to mention that on the show’s home page, Josh points out that the human brain has far more potential than most people realize and that releasing that potential requires people to understand and address the ways in which their brains are limited or shackled. Josh talks about what led him to enter the podcast world and gives an overview of his show. [[01:18:01] Dawn mentions that Josh plays tennis in his spare time, asking if this is something he has always done, or an interest taken up later in life. [01:19:24] Ken asks if it is true that another part of Josh’s daily routine is a walk with his wife. [01:20:19] Ken closes the interview mentioning that a little birdie, perhaps a Georgia Jay, told him that Josh and his family have a special musical tradition at Christmas.
Episode 129: Morley Stone talks about biomimetics and human performance augmentation
Our guest today is Dr. Morley Stone, the former Chief Technology Officer for the Air Force Research Laboratory (AFRL) and former Senior Vice President for Research at Ohio State University, who is now IHMC’s Chief Strategic Partnership Officer. Morley is recognized as an international leader in biomimetics and human performance.
In today’s interview, we talk to Morley about his time as AFRL’s chief technology officer as well as his stint as the chief scientist for the Air Force’s 711th Human Performance Wing, which is responsible for providing technical oversight of projects geared to optimize human performance for the nation’s air, space, and cyberspace forces. We also have a fascinating conversation with Morley about his early career and research into biomimetics, which is the study of using biological structures, materials and principles as models for the development of new materials, structures, and devices.
In his new role at IHMC, Morley will become the institute’s point person for public- and private-sector partnerships. He also will work with IHMC’s scientists and research staff to help coordinate and implement the multitude of scientific projects the institute has in its pipeline.
Show notes:[00:03:07] Dawn mentions that Morley grew up in a small steel producing town in Pennsylvania and asks him what he was like as a kid. [00:03:56] Ken asks Morley about his days as wrestler growing up and why he still today views wrestling as a special sport. [00:05:00] Dawn asks about Morley’s move to Dayton, Ohio, when he was 17. [00:05:36] Dawn asks how Morley decided upon Wright State as opposed to the University of Dayton. [00:05:57] Morley tells the story of how a girl in college pointed out an ad for an internship and how that helped him decide to become a biochemistry major. [00:06:43] Dawn asks what happened to the girl who pointed out the aforementioned ad. [00:08:28] Ken asks Morley to talk about the Air Force Research Lab (AFRL) and the role of the lab’s Materials and Manufacturing Directorate. [00:09:53] Dawn mentions that after earning his bachelor’s degree, Morley had a short stint as a materials research engineer at the directorate before heading off to Carnegie Mellon University to work on a Ph.D. in biochemistry. Dawn asks why Morley chose to attend Carnegie Mellon. [00:11:08] Dawn mentions that in the late ‘80s and early ‘90s, Morley had the good fortune to work with scientists who had the foresight to know that there was going to be a radical change in material science, which up until that point had been dominated by metals and ceramics. Morley talks about the most important lessons he learned from these colleagues and mentors. [00:12:41] Dawn asks about Morley’s time as a research biologist, and eventually principal research biologist, at the Materials and Manufacturing Directorate after his Ph.D. [00:14:41] Ken asks Morley to explain biomimetics and discuss the systems that Morley and his colleagues looked at during his time at the Materials and Manufacturing Directorate, ranging from infrared sensing to instances of biological camouflage. [00:18:01] Dawn mentions that the creation of nanoscale materials for advanced structures has led to a growing interest in the area of biomineralization, she goes on to say that during Morley’s time at the directorate, he especially researched the process of biomineralization and the assembly of nanostructured inorganic components into hierarchical structures, which led to the development of a variety of approaches that mimic the recognition and nucleation capabilities found in biomolecules for inorganic material synthesis. Morley discusses his 2002 paper in Nature Materials where he described the in vitro biosynthesis of silver nanoparticles using silver-binding peptides. [00:21:20] Dawn asks about Morley’s 2004 paper in Advanced Materials where he and his colleagues had taken a protein that was responsible for thermal sensing and incorporated it into an array. [00:23:21] Ken asks about the follow-up paper to Morley’s aforementioned 2004 paper, published in 2005 in the Journal of the American Chemical Society. It was titled “Polypeptide-Templated Synthesis of Hexagonal Silica Platelets.” [00:25:28] Dawn asks Morley about his time as program manager in DARPA’s Defense Science Office from 2003 to 2006. [00:27:30] Morley explains what the Heilmeier Catechism is. [00:28:51] Dawn asks about Morley’s time as senior scientist for Molecular Systems Biotechnology in the Human Effectiveness Directorate of the Air Force Research Laboratory. [00:31:25] Ken mentions that in a 2011 report that ran in The Armed Forces Journal, Morley laid a foundation for how the Department of Defense could play a leadership role in human performance augmentation as a way of developing the “quantified warrior” as he described it. Ken goes on to mention that he cited this paper in a 2014 article he co-authored with Clark Glymour for the Bulletin of Atomic Scientists titled “The Enhanced Warfighter.” Ken asks Morley to talk about his paper and the changes that he has seen in the field since it was published. [00:35:31] Dawn asks what led Morley in 2018 to become the senior vice president for research at Ohio State University. [00:36:33] During a meeting recently held at IHMC, a young academic asked Morley why he left the lab and working directly in applied research to pursue more of a leadership role. Morley responded by saying, “I’m going to be very clear that there’s nothing as fun as when you’re a bench scientist.” Dawn asks Morley why he thinks this. [00:40:00] Ken asks Morley what it is about the various leadership roles that he has had over the years that he finds most rewarding. [00:42:36] Dawn asks why Morley recently joined IHMC and how he sees his new position as the institute’s Chief Strategic Partnership Officer. [00:44:26] Ken mentions that during Morley’s time at DARPA he focused on biologically inspired robotics. Now that Morley is working at IHMC, Ken asks how it feels to be working with a robotics lab that also draws its inspiration from biology. [00:45:40] Ken asks Morley what he likes to do with his spare time now that he and his wife have settled into Pensacola.
Episode 128: Tommy Wood talks about high-fat diets and the metabolic flexibility of the human gut
In today’s episode, Dr. Tommy Wood returns for his fifth appearance on STEM-Talk. Tommy is a UK-trained physician and an assistant research professor of pediatrics at the University of Washington. He also is a visiting research scientist and a valued colleague of ours here at IHMC.
Today’s interview focuses on a new paper that Tommy just had published by the American Society for Microbiology. It’s titled, “Reframing Nutritional Microbiota Studies To Reflect an Inherent Metabolic Flexibility of the Human Gut: A Narrative Review Focusing on High-Fat Diets.”
We discuss the paper and follow up on some research Tommy has done since his last appearance on STEM-Talk, a two-part interview that took place a little more than a year ago. In that two-part interview, episodes 110 and 111, we touched on Tommy’s research into the importance of metabolic health and how only one in eight Americans is considered metabolically healthy.
We also talk to Tommy about a new grant he just received to examine the effects of azithromycin on premature brain injury in a ferret model. As part of this grant, Tommy will be collaborating with his wife, Dr. Elizabeth Nance, who also is an assistant professor at the University of Washington and was our guest on episode 71 of STEM-Talk.
Show notes:[00:03:15] Dawn opens the interview mentioning Tommy’s new paper published by the American Society for Microbiology titled “Reframing Nutritional Microbiota Studies to Reflect an Inherent Metabolic Flexibility of the Human Gut: A Narrative Review Focusing on High-Fat Diets.” Dawn mentions that in our last interview with Tommy, he talked about the importance of insulin sensitivity and metabolic health, yet as Tommy has pointed out, more than 80 percent of Americans have some kind of metabolic disease or dysfunction. Given that, Dawn asks Tommy to revisit key points regarding insulin resistance; the importance of metabolic health; and why so many Americans struggle with this issue. [00:06:18] Ken points out that the common view held in much of the nutritional-microbiota research is that high-fat diets are harmful to human health, at least in part through their modulation of the gut microbiota. Ken goes on to say that there are a number of studies that support the inherent flexibility of the human gut and our microbiota’s ability to adapt to a variety of food sources, suggesting a more nuanced picture than the commonly held view. Ken asks Tommy to give an overview of the gut microbiome and how research in the past decade has explored the effects of the gut microbiome on our metabolism, immune systems, our sleep, and our moods and cognition. [00:09:50] Dawn asks Tommy to explain the history of how fat, and high-fat diets, became public enemy number one in many circles, including gut microbiome research. [00:12:46] Ken mentions that there are many limitations when it comes to preclinical nutritional research, with many studies on the role of fat in the diet being based on animal models, particularly rat models, which presents several problems since the natural diet of a mouse is low in fat and high in carbohydrates. [00:15:50] Ken asks Tommy about the need for a more nuanced view of fat and our microbiota’s ability to adapt to different food sources. [00:17:33] Ken points out that while people might throw around the term “healthy gut microbiota,” the research into the gut microbiota is so new that we don’t yet know for sure what a healthy gut microbiota should look like. [00:21:22] Ken asks Tommy how we should go about reframing the debate about fat and high-fat diets to better reflect the overall evidence. [00:23:48] Dawn mentions that in the past decade, researchers have significantly improved our understanding of the gut microbiome. She asks about Tommy’s belief that there is a need to understand the gut microbiome in an evolutionary context as well. [00:25:18] Tommy gives an overview of the gut-barrier function and its role in health and disease. [00:25:31] Dawn asks Tommy to talk about the significance of the study by Duke University’s David Lawrence that Tommy cited in his aforementioned paper, which highlights how quickly and reliably the human gut microbiota adapts to dietary changes. [00:30:42] Dawn mentions that there is a lot of research supporting the therapeutic effects of a ketogenic diet on overall health in the context of epilepsy and multiple sclerosis. She asks if there is any such research that focuses on the gut. [00:34:01] Dawn asks about the assertion in Tommy’s aforementioned paper that while butyrate production may be reduced on a ketogenic diet, other molecules can potentially take butyrate’s place to maintain the gut barrier function, an assertion that challenges many assumptions about normal metabolic pathways in the gut. [00:36:21] Ken asks if there have been any studies that Tommy knows of that have assessed the effects of ketones, or a ketogenic diet, on the gut barrier function. [00:39:50] Dawn asks about the mouse models and preclinical studies that show that ketogenic diets or ketones are cancer suppressive. [00:40:52] Ken mentions that Tommy addresses three objections concerning the effects of fat and protein on our gut microbiota in his paper, asking Tommy to briefly go over these objections and his responses to them. [00:45:42] Dawn asks Tommy what he believes are the questions that need to be asked or answered when it comes to nutritional microbiota research. [00:46:36] Dawn mentions Tommy’s 2020 IHMC evening lecture about nourishing the human brain titled “Brain Health Across the Lifespan.” Dawn asks about the grant Tommy just received to examine the effects of azithromycin on premature brain injury in a ferret model. [00:48:35] Dawn asks Tommy what it is about azithromycin that he finds particularly exciting as a potential neuroprotective agent. [00:50:52] Ken mentions that Tommy will be collaborating on the grant with his wife, Dr. Elizabeth Nance, a faculty member of the University of Washington who was our guest on episode 71 of STEM-Talk. Ken asks Tommy how he and his wife’s work on this project will intersect. [00:53:42] Dawn asks Tommy how Elizabeth is doing. [00:54:26] Ken asks how Tommy’s findings on neuroprotection in babies might be transferable to adults looking to optimize their neural health. [00:59:02] Dawn closes the interview asking Tommy about his dogs and his most important goal in life.
Episode 127: From UFOs to fasting to the keto flu, Ken & Dawn answer questions
It’s time for another Ask Me Anything episode. In today’s show, Ken and Dawn tackle a wide range of listener questions about:
— Protein intake on a ketogenic diet.
— A new study on the efficacy and safety of MDMA-assisted therapy.
— The Pentagon’s new report about UFOs.
— Virta Health’s two-year pilot study that demonstrated people diagnosed with prediabetes had normalized their glucose through carbohydrate restriction.
— The FDA’s controversial approval of the Biogen Alzheimer’s disease drug Aduhelm.
— The deepest man-made pool and diving research facility that just opened in Dubai.
— Strategies to deal with the so-called “keto flu.”
— And a lot more. Enjoy.
00:02:49 A listener asks Ken about protein intake on a ketogenic diet. The listener says they have heard some experts say that protein intake should be fairly low on a ketogenic diet while other experts suggest protein needs might actually be higher than what is generally recommended. The listener, who is physically active and on a ketogenic diet but isn’t seeing much muscle growth, asks Ken what the research says about what proper levels of protein on a ketogenic diet.
00:05:05 A listener asks Ken about STEM-Talk’s interview with Gordon Lithgow, episode 120 of STEM-Talk, mentioning that Ken and Gordon referenced arginine AKG, a supplement often used by athletes and bodybuilders to improve their performance and reduce muscle fatigue. The listener asks if arginine AKG, or calcium AKG, or something else can help them recover from exercise as they get older. In his response, Ken discusses a 2017 meta-analysis by Robert Wolfe. Ken also mentions two essential amino acid blends, MAP Master Amino Acid Pattern. The other blend is called Mass Pro Synthagen.
00:12:09 A listener mentions in their question that there is a new study that just came out in Nature Medicine looking at the efficacy and safety of MDMA-assisted therapy for people diagnosed with severe PTSD. Nearly 70 percent of the participants who received MDMA therapy no longer qualified for a diagnosis of PTSD after two months of treatment. The listener asks Ken and Dawn if they have read this study and what their thoughts are. Ken in his response mentions two STEM-Talk episodes that touched on MDMA-assisted therapy, David Rabin in Episode 99 and Rachel Yehuda in episode 101.
00:14:37]A listener asks Ken what the justification for spending almost $3 billion on the Perseverance Mars mission is, going on to ask with all the needs here on Earth, how does NASA and Congress justify the billions that will be needed for a manned mission to Mars.
00:19:06 A listener asks how Dawn’s research on glymphatic function in extreme environments is going.
00:22:31 A listener asks Kens for his thoughts on the recent media coverage of the Pentagon’s new report on more 100 UFOs, or “unidentified aerial phenomena,” that the Pentagon cannot explain.
00:25:49 A listener mentions that Virta Health is wrapping up its data collection of a five-year trial that looks at nutritional ketosis as a treatment for type-2 diabetes and prediabetes. Virta recently published the results of its two-year pilot study that demonstrated people diagnosed with prediabetes had normalized their glucose in the blood through carbohydrate restriction. The listener asks Ken to comment on this two-year pilot study since Ken is affiliated with Virta. In his response, Ken mentions Amy McKenzie’s 2021 paper.
00:27:17 A listener asks Ken about the controversial FDA approval of the Biogen Alzheimer’s disease drug Aduhelm. Despite murky clinical trial results, the drug was fast-tracked, even though it will cost a person $56,000 annually.
00:30:57 A listener asks Dawn, given her diving background, about the deepest man-made pool and diving research facility that just opened in Dubai.
00:33:44 A listener asks Ken about a study that ran in JAMA that found that fasting for 12 hours or more led to minimal weight loss and significant muscle loss. The listener mentions that these results go against the research of some previous STEM-Talk guests like Satchin Panda, and asks Ken to weigh in on these results and the design of the study. In his response, Ken refers to several well-done studies and a 2019 paper by Tinsley, titled, “Time Rest Restricted Feeding Plus Resistance Training In Active Females, a Randomized Trial.”
00:37:21 A listener asks Ken about the new center for human performance that IHMC is looking to build in Pensacola.
00:38:07 A listener mentions a study that ran in PLOS Medicine which reported that men and women whose workout routines consistently included resistance exercise were less likely to become obese. The listener asks if, based on this, whether what we do in terms of exercise, particularly resistance training, is just as important as the foods we eat and the diets we follow.
00:40:28 A listener mentions Dawn’s research in neuroprotection in stressful environments and asks if Dawn is also looking at applying these findings to clinical scenarios, such as surgery, anesthesia, and radiation.
00:42:00 A listener asks Ken about how to deal with the “keto flu” mentioning that he remembers being given salt tablets by his coach when he was younger, but is unable to find them now. In his response, Ken mentions Robb Wolf’s LMNT electrolyte product and an article on Virta Health’s website that addresses electrolytes and the importance of managing potassium and sodium as part of a well-formulated ketogenic diet.
Episode 126: Christoffer Clemmensen discusses therapeutic strategies to correct obesity and its disorders
Our guest today is Dr. Christoffer Clemmensen, an associate professor and lead researcher at the University of Copenhagen’s Novo Nordisk Foundation Center for Basic Metabolic Research.
Christoffer’s lab at the university explores pharmacological and therapeutic treatments for obesity and its related diseases and disorders. He and his colleagues focus on dissecting the neuroendocrine signals involved in coordinating appetite, food-motivated behavior, energy expenditure, glycemic control, and lipid metabolism.
We have a fascinating discussion with Christoffer about his lab’s efforts to turn molecular and physiological insights into innovative therapeutic strategies that Christoffer hopes someday can reduce obesity and its associated metabolic disorders. Christoffer is a native of Denmark who earned his Ph.D. in Molecular Pharmacology from the University of Copenhagen in 2013.
Joining Ken for today’s interview is IHMC colleague and senior research scientist Dr. Marcas Bamman, who was our guest on episode 116. Marcas is the founder and former director of the University of Alabama at Birmingham Center for Exercise Medicine. Marcas joined IHMC last year as a Senior Research Scientist.
Show notes:[00:03:24] Marcas asks Christoffer about growing up in a small rural town in Denmark in the 1980s and ‘90s. [00:04:05] Christoffer’s talks about his days as an elite tennis player when he was a youth. [00:04:41] Ken asks Christoffer when he first became interested in science. [00:05:48] Marcas asks Christoffer what changed his mind about wanting to study computer science at university. [00:07:04] Christoffer explains how he decided to attend University of Copenhagen. [00:08:19] Marcas mentions that Christoffer’s original focus at university was on exercise biology, but that he became fascinated by the mechanisms of obesity and that interest took him in a new direction. Marcas asks how that shift in interest came about. [00:10:01] Marcas follows up on the previous question and asks if there were a particular instance that persuaded Christoffer to switch from focusing on exercise to focusing more on weight control and obesity. [00:10:40] Ken asks what led Christopher to pursue a Ph.D. in molecular pharmacology after attaining a bachelor’s degree in exercise biology and a master’s degree in human biology. [00:12:11] Marcas asks Christoffer why he went to Munich, Germany, as a postdoctoral fellow at the Helmholtz Diabetes Center after completing his post-doc at the University of Copenhagen. [00:14:00] After mentioning that Christoffer eventually became the group leader at Helmholtz, Ken asks Christoffer why he then transitioned back to the University of Copenhagen. [00:14:52] Marcas asks Christopher to talk about the big questions that get to the heart of his research. [00:16:20] Ken mentions that Christoffer is now an associate professor at the Nova Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen, where he is the head of the Clemmensen Group. Ken goes on to mention that the Clemmensen Group’s website says the lab focuses on dissecting the neuroendocrine signals that coordinate appetite regulation, food-motivated behavior, energy expenditure, glycemic control, and lipid metabolism. Ken asks if Christoffer could give an overview of what all these research focuses entail. [00:18:17] Marcas mentions that obesity and its related diseases, such as type-2 diabetes and cardiovascular disease, have become serious problems affecting the world’s public health and global economy. Marcas goes on to say that Christoffer’s 2019 paper titled “Emerging hormonal-based combination pharmacotherapies for the treatment of metabolic diseases” makes the observation that the treatments we have been using to deal with this problem have not been able to effectively reverse the staggering rates of obesity we’re witnessing around the world. Marcas asks Christoffer to talk about this paper and how it underscored the need for better treatments of obesity. [00:19:48] In light of the need to target multiple signaling pathways to effectively treat obesity that Christoffer described in his 2019 paper, Ken asks Christoffer to explain the hormonal-based pharmacotherapies that he has been looking into as potential treatments for obesity. [00:21:58] Marcas asks Christoffer why an overwhelming majority of people who do manage to lose weight end up gaining the weight back, and what are the most effective therapies to help keep the pounds off once a person does lose weight. [00:23:56] Marcas mentions that Christoffer followed his 2019 paper with a review in PLOS Biology that looked at the evolutionary and environmental perspectives on human body weight. The paper asks the question, “Why are we not all obese?” Marcas, considering that poignant question, asks Christoffer why everyone isn’t prone to gaining weight in the same way. [00:26:44] Ken mentions that he has heavy doubts that our species experienced a recent biological change that would have caused a massive increase in obesity within the last 30-80 years, given that only a few decades ago most people were slender. [00:27:52] Marcas asks about the elusive slimming gene, mentioning that biologists have identified the physiological agents that keep our fat mass from becoming too low, but have had trouble understanding the exact mechanisms that regulate excess fat. He asks Christoffer to expound upon the current research as well as evidence dating back to the 1950s for the existence of a blood-borne, weight-gain preventive molecule. [00:30:09] Ken asks Christoffer about other factors that regulate energy balance in the body. [00:32:10] In light of the fact that a chronic state of positive energy balance leads to weight gain, Ken asks Christoffer what he believes is the key pathway to target, whether it be appetite control, energy expenditure, or a combination of both. [00:34:14] Marcas asks Christoffer to explain the remarkable differences between brown fat and white fat, and in this context to summarize his 2018 paper in nature communicationsthat described the potent effects of stimulating brown fat thermogenesis with a drug called icilin. [00:37:14] Marcas mentions that Christoffer’s paper in PLOS Biology addressed how geneticists are starting to uncover potential weight-gain defense genes. The paper, however, argues that for humans to fully benefit from such research, physiologists will have to play a role in the interpretation of such genetic discoveries. Marcas asks Christoffer what kind of collaboration he thinks is necessary between physiologists and geneticists. [00:39:08] Ken asks if the fact that the human genome has stayed stable throughout the rise in obesity over the past several decades suggests that epigenetic modifications play a role, and if Christoffer thinks that differences in obesity susceptibility across individuals might be partially explained by differences in the epigenome. [00:41:28] Marcas asks what the current status of pharmacological obesity treatment is and if Christoffer anticipates that landscape changing in the near future. [00:43:43] In terms of translating promising results in rodents to humans, Ken asks Christoffer to describe the specific challenges we face in using rodents to understand obesity in humans. [00:47:18] Ken mentions the overreliance on weight and BMI as measurements as opposed to body composition, which depreciates the value of muscle as an energy storing organ. [00:49:03] Marcas mentions that the model for pharmacological treatment of obesity seems to be leaning towards suppression of appetite. Marcas asks if such an agent were to be found, how successful does Christoffer think it would be in the long term if the pharmacotherapy was given in the absence of a behavioral change. [00:51:16] Marcas asks Christoffer to elaborate on his belief in the importance of omic-methods as well as how he is using such methods in his own research. [00:53:17] Ken asks about the greatest benefits, as well as the challenges, of using an untargeted approach to metabolomics profiling, which Christoffer wrote about in his 2020 article addressing molecular changes in the body following bouts of endurance and resistance exercise. [00:56:05] Ken asks how Christoffer decided which metabolites to study more closely in the aforementioned study. [00:57:14] Marcas mentions that Christoffer’s aforementioned 2020 study focused on physiological changes that took place within a few hours of exercise. Marcas goes on to mention that efforts are underway to better understand such acute molecular changes in the context of longer-term training, as the acute responses to exercise in a sedentary human are likely to be much different than the acute response of a trained individual. Marcas asks how we can learn from the range of responses in trained vs. untrained states as it pertains to weight management mechanisms or other health benefits. [00:59:08] Marcas brings up Christoffer’s most recent paper published earlier this year in Nature Communication, in which Christoffer asks the question: How does the exercise-and-appetite-related protein GDF15 act in different contexts? Marcas goes on to mention that the paper found that GDF15 acts differently based on whether it is endogenously produced or pharmacologically applied and asks Christoffer to talk about this in more depth. [01:04:00] Marcas explains that exercise-response molecules, of which there are a number, are dose dependent, which is to say that they are produced more, or stay in the body longer, depending on the mode and or intensity of the exercise. He goes on to ask if GDF15 has any dose dependency associated with it in respect to the magnitude of elevation and time it stays elevated. [01:06:30] Marcas congratulates Christoffer on his research gaining more attention and his lab growing to about a dozen people. [01:07:57] Marcas asks Christoffer what he does to stay in shape and if he still plays tennis. [01:08:52] Ken closes the interview asking if this is Christoffer’s first podcast interview in English and if Christoffer enjoys listening to podcasts.