STEM-Talk

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. Links: Kaleen Lavin bio Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio  

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. Links: Matt Kaeberlein bio Kaeberlein lab Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio  

Today’s guest is Dr. Mark Lewis, executive director of NDIA’s Emerging Technologies Institute (NDIA ETI), a nonpartisan 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. Links: Mark Lewis bio Learn more about IHMC STEM-Talk homepage  Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio

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.    

British researcher Greg Potter discusses circadian biology and the importance of sleep. He shares his academic background and interest in circadian biology, childhood interests, journey into sports science, and development of interest in circadian rhythms and sleep. He also explores the roles of peripheral clocks in glucose regulation and cardiovascular function, the impact of the social clock on humans, and the implications of shift work on health and performance.

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. Links: Elaine Lee Lab Elaine Choung-Hee Lee bio Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio

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. Links: Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio  Mike Griffin bio  

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. Links: Mark Mattson bio Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio    

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,[85] 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. Links: Martin Kulldorff  Brownstone Institute page Martin Kulldorff Wikipedia page Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio    

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. Links: Christopher Logothetis bio Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio