STEM-Talk

Dr. Keith Baar joins Ken and Dawn today for the second of his two-part interview for STEM-Talk. Keith is a renowned scientist in the emerging field of molecular exercise physiology who has made fundamental discoveries on how muscles grow bigger, stronger, and more fatigue resistant. He is the head of the Functional Molecular Biology Laboratory in the Department of Neurobiology, Physiology, and Behavior at the University of California, Davis. In his lab, he leads a team of researchers attempting to develop ways to improve muscle, tendon and ligament function. Part one of our interview, episode 62, covered Keith’s childhood in Canada and his undergrad years at the University of Michigan as well as his time at the University of California, Berkeley, where he earned a master’s degree in human biophysics. We talked about Keith’s work at the University of Illinois, where he received a doctorate in physiology and biophysics. We also covered Keith’s time in the lab of John Holloszy, who is known as the father of exercise research in the United States, as well as the five years Keith spent at the University of Dundee in Scotland. Episode 63 picks up with Keith explaining his decision to return to the states and join the faculty at the University of California, Davis.  Ken and Dawn then talk to Keith about his most recent research, some of which is looking at how to determine the best way to train, as well as what types of foods compliment training to decrease tendon and ligament injury and accelerate return to play. This work has the potential to improve muscle function not only in athletes, but also improve people’s quality of life as they age. Another key topic covered in part two of our interview is the research Keith is doing on a ketogenic diet and its potential to reduce cancer rates and improve cognition. Keith also provides his thoughts on what optimal workouts and nutrition should look like. Links: Baar’s UC Davis physiology department bio: https://www.ucdmc.ucdavis.edu/physiology/faculty/baar.html Baar’s UC Davis biology department bio: https://biology.ucdavis.edu/people/keith-baar Functional Molecular Biology Lab website: http://www.fmblab.com/  Molecular brakes regulating mTORC1 activation in skeletal muscle paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4137116/ Age-related Differences in Dystrophin article: https://www.ncbi.nlm.nih.gov/pubmed/27382038 Show notes: 2:54: Dawn begins part 2 of our interview by mentioning that for the past eight years, Keith has been working at the University of California Davis. She asks Keith what prompted him to return to the U.S. from Scotland and join the faculty at UC Davis. 3:37: Dawn points out that Keith’s Functional Molecular Biology Lab conducts research across a range of related topics, including musculoskeletal development and adaptation as well as methods for engineering functional musculoskeletal tissues in vitro. She asks Keith to give a high-level overview of some of that research. 4:16: Dawn comments that some of Keith’s recent work has shown that we can use specific nutrition and training strategies to optimize injury recovery and prevention. She goes on to say that musculoskeletal injuries are among the most common problems that active people have. 8:45: Ken talks about how Keith has noted that tendon stiffness is dependent upon collagen content, and the amount of crosslinks within. He goes on to mention that Keith has developed various training modalities, as well as nutritional protocols, that can increase and decrease tendon stiffness. Ken begins this line of inquiry by asking about the training methods for this purpose. 12:04: Following up on the previous question, Ken asks whether anyone has looked at how blood flow restriction training, which is increasing in popularity, affects tendon stiffness. 13:32: Dawn moves on to asking about nutrition. She mentions that Keith’s lab has done a great deal of groundbreaking work on the use of gelatin and a small amount of vitamin C to augment collagen synthesis in tendons, ligaments, cartilage, and bone. She asks if he could talk about this nutrition protocol and its effects, particularly when combined with jumping rope. 17:52: Ken mentions that this work is not only interesting scientifically, but it has an immediate, practical application that people can use in their life. Ken goes on to say that those suffering from stress fractures or a variety of other ailments could benefit from this. 21:09: Ken mentions that there are several different forms of collagen, asking if there is any particularly efficacious form, or if they function equally. 22:40: Ken comments that it is not just lower body weakness and injuries in tendons, but also tendonitis that is found in the shoulders and elbows. He asks if there is a variant of Keith’s protocol that is suited for this sort of tendonitis as well. 24:37: Ken asks a question submitted by friends in the special ops community. He mentions that one of their biggest issues is force absorption, due to the repeated, substantial, damage accrued in both training and in operations. He goes on to ask if a focus on eccentric training would lengthen fascicles to allow for greater absorption, and how does it influence the ability to contract concentrically. 26:13: Dawn mentions that she has heard Keith discuss “sugar cross-linking” in the context of aging and diabetes. She asks if this explains why diabetics suffer an increased incidence of tendon and ligament ruptures and injuries. 28:22: Ken, coming back to tendon stiffness, mentions that in addition to fast exercise, inactivity also leads to increased tendon stiffness, counterintuitive as that is. He asks if Keith could discuss this, somewhat surprising, fact. 30:20: Ken comments that ligament engineering is another fascinating area of Keith’s research; he goes on to say that Keith and his colleagues recently engineered the first in vitro ligaments. He goes on to inquire as to how these ligaments are created, what insights can be gleaned from them, and how Keith sees them being used in the future. 34:23: Ken states that mTOR inhibition by rapamycin is arguably the only strategy that has reliably resulted in lifespan extension across a multitude of different species. He goes on to say that we know that mTORC1 activation increases muscle mass and strength, which is critical for optimizing health span into old age. He goes on to bring up a recent paper Keith co-authored with Megan Roberts that showed the ketogenic diet had tissue-specific effects on mTORC1 signaling; decreasing signaling in the liver, while increasing it in the muscle. Ken postulates that perhaps researchers should focus their attention on tissue-specific mTOR activity, to further elucidate the issue of balancing mTOR for longevity with the maintenance of muscle for strength quality. Ken asks Keith if he had unlimited resources, how would Keith design a study to explore this. 43:32: Ken asks if Keith is familiar with a class of drugs that one could characterize as PPAR-delta agonists, sometimes called exercise mimetics, given the overlap between the effects of the ketogenic diet and this class of drugs. 45:10: In regards to longevity, Dawn mentions that few would argue that many elite athletes train for performance at the expense of health. She asks what would be Keith’s overall training recommendation for someone who wants to maximize healthspan and lifespan, and if that is possible while also striving for top levels of performance. 49:24: Ken comments on a belief in the world of “bro science,” that post-exercise carbohydrate ingestion is absolutely necessary for maximizing the anabolic response of resistance training. Ken asks if this is true, and if not, if Keith would educate us as to why and what optimal nutrition and workouts should look like. 51:18: Ken asks what Keith sees as the role of autophagy in the maintenance of muscle mass in aging adults. 53:48: Ken comments on the phenomenon of older people developing anabolic resistance, much like insulin resistance; mentioning a paper that recently looked at the ketogenic diet in that context and found it increased IGF-1 receptor sensitivity. 54:46: Dawn asks to what extent does Keith think a person’s baseline body composition can impact the response to an exercise stimulus. 55:44: Ken points out that Keith has been a scientific advisor for a number of different athletic teams and organizations, pointing out that Keith works to maximize the effects of training for both endurance and strength as well as ways to minimize injury. Ken asks Keith what that experience has been like. 58:27: Ken mentions his intrigue with the mission statement of Keith’s Functional Molecular Biology Lab: “To perform world class musculoskeletal research in a family environment.” Ken asks Keith to explain the story behind including “a family environment” in his mission statement. 1:01:08: Interview ends.

Today’s episode is the first of a two-part interview with Dr. Keith Baar, the head of the Functional Molecular Biology Laboratory in the Department of Neurobiology, Physiology, and Behavior at the University of California, Davis. In his capacity as a researcher, Keith has made fundamental discoveries on how muscle grows bigger, stronger, and more fatigue resistant. He is a renowned scientist in the emerging field of molecular exercise physiology, and is leading a team of researchers attempting to develop ways to improve muscle, tendon and ligament function. Part one of our interview features our conversation with Keith about his background and his time time in the lab of John Holloszy, who is known as the father of exercise research in the United States. Episode 63 of STEM-Talk has Dawn and Ken talking to Keith about his most recent research, which is looking at how to determine the best way to train, as well as what types of foods compliment training to decrease tendon and ligament injury and accelerate return to play. This work has the potential to improve muscle function and people’s quality of life, especially as they age. Ken and Dawn also have a conversation with Keith about the research he is doing on a ketogenic diet and its potential to reduce cancer rates and improve cognition. Links: UC Davis physiology department bio: https://www.ucdmc.ucdavis.edu/physiology/faculty/baar.html UC Davis biology department bio” https://biology.ucdavis.edu/people/keith-baar Functional Molecular Biology Lab website: http://www.fmblab.com Molecular brakes regulating mTORC1 activation in skeletal muscle paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4137116/ Age-related Differences in Dystrophin article: https://www.ncbi.nlm.nih.gov/pubmed/27382038  Show notes: 3:14: Dawn opens the interview by mentioning that Keith grew up in Canada, and asks what he was like as a child. 4:02: Dawn asks if Keith was interested in science as a kid. 4:53: Dawn comments that after high school, Keith came to the U.S. to attend the University of Michigan, where he earned a bachelor’s degree in kinesiology. She Keith if Michigan was where he first became interested in the science of how muscles work. 7:54: Dawn asks Keith if he played any sports at Michigan. 8:34: Dawn asks what lead Keith to attend the University of California, Berkeley to pursue a master’s degree in human biophysics. 9:39: Dawn mentions that after his time at Berkeley, Keith returned to the Midwest to attend the University of Illinois where he received his doctorate in physiology and biophysics. She asks why he decided on Illinois for his doctoral work. 11:12: Ken mentions that Keith’s Ph.D. work focused on the effect of resistance exercise on specific molecular markers that are related to muscle growth. He goes on to say that Keith identified that mTOR complex 1 was activated in response to resistance exercise and that the activation was proportional to the load across the muscle. He asks Keith to talk about this work and its significance. 16:20: Ken comments how surprising that discovery must have been. 17:33: Ken asks Keith to explain the two basic ways of activating mTORC1 in skeletal muscle. Ken also asks whether these two are merely additive, or if together they elicit a greater muscle protein response than either would independently. 29:49: Dawn mentions that after Illinois, Keith went to work in the lab of John Holloszy at Washington University in St. Louis, a professor of medicine who is known as the father of exercise research in the United States. Dawn asks if is Holloszy is the one who discovered that when people do endurance exercise that their muscles accumulate more mitochondria. 32:24: Ken asks about the role of PGC-1a. 38:43: Ken comments that we know most sports require a combination of strength and endurance for optimal performance, bringing up the topic of concurrent training. 48:02: Ken asks if we know which form of AMPK is activated by things such as Metformin or the ketogenic diet. 49:24: Dawn comments that Keith eventually accepted a position at Michigan where he worked with Bob Denis, who figured out how to engineer muscles as well as ligaments. She asks Keith to share some things about the research they did together. 50:41: Dawn mentions that after Michigan, Keith accepted a position at the University of Dundee in Scotland, where he worked for 5 years. Dawn asks what that experience was like. 55:20: Ken mentions that from looking at the literature, it seems as though Keith discovered that the non-contractile portion of the muscle plays a key role in the transfer of force, and that this is nearly as important as the size of the muscle fiber itself. He asks Keith to elaborate on this finding. 58:45: Ken asks if Keith’s work has elucidated a potential countermeasure to the loss of dystrophin, for both the aging population and cancer patients. Keith then talks about research at the University of California, San Diego, that has shown the beneficial effects epicatechin, a flavanol in dark chocolate. 1:00:37: Ken mentions that some athletes are using Transdermal Epicatechin, and asks about the efficacy of such practice. 1:01:54: Interview ends.

More than 90 Americans a day are dying from opioid abuse. Today’s guest, Dr. Christopher McCurdy, is at the forefront of research designed to help the U.S. deal with this drug overdose crisis. Chris is a medicinal chemist and behavioral pharmacologist at the University of Florida who is internationally known as an expert on kratom, a botanical mixture that has been shown to help people struggling with addiction. He recently became president of the American Association of Pharmaceutical Scientists, and has spent his career focusing on the design, synthesis and development of drugs to treat pain and drug abuse. Chris earned his bachelor of science degree in pharmacy from Ohio Northern University, and a Ph.D. in medicinal chemistry from the University of Georgia College of Pharmacy in 1998. He did his postdoctoral work at the University of Minnesota where he focused on opiate chemistry in relation to drug abuse and drug addiction. He joined the faculty at the University of Mississippi in 2001 where much of his research was successful in discovering unique and selective tools for sigma receptors, NPFF receptors and opioid receptors. Dr. McCurdy accepted a post as a professor of medicinal chemistry at Florida in 2017 and became the director of the university’s Translational Drug Development Core.  Links:  Christopher McCurdy UF faculty page: http://pharmacy.ufl.edu/faculty/christopher-mccurdy/ American Association of Pharmaceutical Scientists: https://www.aaps.org/home Translational Drug Development Core: https://www.ctsi.ufl.edu/research/laboratory-services/translational-drug-development-core/  Suspected Adulteration of Commercial Kratom Products with Hydroxymitragyine: https://www.ncbi.nlm.nih.gov/pubmed/27752985 Self-treatment of Opioid Withdrawal Using Kratom: https://www.ncbi.nlm.nih.gov/pubmed/18482427 Herbal Medicines for the Management of Opioid Addiction: https://www.ncbi.nlm.nih.gov/pubmed/22133323 Show notes:  2:58: Ken opens by asking Chris if he ever dreamed of becoming a professional athlete as a result of growing up in Pittsburg during the hay-day of the Stealers and the Pirates. 3:28: Dawn mentions that Chris’s father was a pharmacist, and his mother, a science teacher. She further mentions that in addition to being interested in sports, that Chris also was interested in science, and she asks what role his parents played in that. 4:45: Dawn mentions that Chris moved to a suburb of Youngstown Ohio just as he was starting high school. Chris talks about playing basketball, being part of a competitive swim team, and his reputation as a fairly straight-laced kid. 5:27: Ken mentions that Chris headed to Ohio Northern University after he graduated from high-school and initially pursued a double major in pharmacy and music. Ken asks what prompted that particular combination. 6:39: Ken talks about how at Ohio Northern, Chris’s first real mentor in science noted his talent for research, and suggested that Chris should head to the University of Georgia for the summer to get acquainted with research. Chris talks about how that eventually led to him attend Georgia for his doctorate. 10:39: Ken asks Chris to talk about his doctoral research into Native American Tobacco. 13:28: Dawn comments on how there weren’t too many post-doc opportunities available at the time he finished his studies at Georgia, but that she understands there is an apparent pattern in his life of being at the right place at the right time. She asks if it was this pattern that lead him to the University of Minnesota. 17:05: Dawn inquires as to what got Chris interested in working on the natural product called Salvinorin A (Magic Mint), and what became of that research. 20:40: Dawn mentions that because of his work on salvia divinorum, Chris was invited by the National Institute of Drug Abuse to give a talk in 2004, which is where he first learned about kratom. 23:08: As context, Ken asks if Chris could expound upon kratom’s history, the different types of kratom, and the varying effects they have on users. 32:10: Ken brings up the debate surrounding whether kratom is properly construed as an opioid. Chris goes on to talk about the differences between kratom and classic opioids. 37:33: Following up on the previous question, Ken mentions that the distinction between opioid and opiate is quite important, given that when people talk of opioids they are generally thinking of opiates specifically. Given that respiratory depression is a major issue for those on opiates, Ken asks how many lives could be saved by moving people off opiates. 40:32: Shifting the conversation, Ken asks about the use of kratom among athletes. 43:10: Ken, following up on the last question, mentions that the primary use of kratom among athletes is not for performance enhancement, but rather recovery, and coping with the pain.  One frequently hears of kratom use among athletes, especially those engaged in sports such as wrestling, mix martial arts, bodybuilding, and football to help manage the pain associated with their sport-related injuries. 47:08: Ken comments on the importance of Chris’s endeavor to perform clinical trials with kratom, and asks about the resistance he has faced in doing trials. 50:17: Dawn asks if there are any documented side effects of chronic use of kratom, and if there is the potential to overdose. 53:49: Dawn, shifting gears, mentions that while at the University of Mississippi he met Bonnie Avery, an analytical chemist, and that he began to collaborate with her. Dawn goes on to mention that Bonnie became known as the bearer of bad news, asking how she ended up with that reputation, and also how Chris ended up marrying Bonnie. 57:10: Dawn says that in 2013 the Florida Legislature announced that it was going to create a preeminence program that would provide state universities millions of dollars to attract top level faculty members and scientists. She mentions that because of this program Chris was approached, and that he and Bonnie eventually joined the Florida faculty. Dawn asks how that all came about. 59:39: Dawn asks Chris about a mentor who once advised him, “Always focus on the science, and be true to the science.” Dawn asks Chris if that is advice he, too, shares with people. 1:01:55: Interview ends.

Why is it that modern marine concrete structures crumble and corrode within decades, but 2,000-year-old Roman piers and breakwaters endure to this day? Episode 60 of STEM-Talk features Dr. Marie Jackson, a scientist who has spent the past two decades figuring out the answer to that and other questions about the durability of ancient Roman mortars and concretes. Marie is a research associate professor in the department of geology and geophysics at the University of Utah. She is known for her investigations in pyroclastic volcanism, mineralogy, materials science, and archaeological science that are breaking new ground in understanding the durability and specialty properties in ancient Roman mortars and concretes. She is particularly focused on deciphering Roman methods and materials in the hope of producing innovative, environmentally friendly cementitious masonry products and nuclear waste storage materials that would benefit the modern world. She was the lead principal investigator of a drilling project in the summer of 2017 on the Surtsey Volcano, which is on a small isolated island off the coast of Iceland. The volcano is growing the same mineral cements as Roman marine cement and the drilling project is helping provide extraordinary insights into the materials and processes the Romans used. She is particularly focused on deciphering Roman methods and materials in the hope of producing innovative, environmentally friendly cementitious masonry products and nuclear waste storage materials that would benefit the modern world. She was the lead principle investigator of a drilling project in the summer of 2017 on the Surtsey Volcano, which is on a small isolated island off the coast of Iceland. The volcano is growing the same mineral cements as Roman marine cement and the drilling project is helping provide extraordinary insights into the materials and processes the Romans used. After receiving her bachelor of science in earth sciences from the University of California Santa Cruz, Marie traveled overseas and received a doctorate from the Universite de Nantes in France. She returned stateside and received a doctor of philosophy from John Hopkins University as well as a Ph.D. in earth and planetary sciences. Marie then went to work as a research geoscientist for the U.S. Geological Survey. After taking time off to raise a family, Marie joined the department of civil and environmental engineering at the University of California, Berkeley, as a project scientist. She stepped into her current position at the University of Utah in 2016. Links: Mechanical resilience and cementitious processes in Imperial Roman architectural mortar: https://www.researchgate.net/publication/270161645_Mechanical_resilience_and_cementitious_processes_in_Imperial_Roman_architectural_mortar Marie Jackson ResearchGate profile: https://www.researchgate.net/profile/Marie_Jackson Surtsey blogspace: https://surtsey50years.utah.edu  Show notes:  4:06: Dawn begins interview by mentioning Marie’s love of the outdoors as a child and asks her to talk about those days. 4:38: Dawn asks if Marie’s father, who was a geologist, contributed to her love of the outdoors. 5:11: Dawn asks what topics Marie was interested in while in high school. 5:44: Dawn mentions that when Marie went to college, she never envisioned herself as a scientist, but this changed in her junior year, when her interest in earth sciences took root. Dawn asks Marie to elaborate on how that happened. 6:27: Ken asks Marie what role, if any, her family’s ranch played in motivating her interest in geology. 7:22: Dawn mentions that after college Marie worked for a mining company for a few years, which enabled her to save enough money to travel to France, where she worked on a doctorate. She asks if this is how Marie ended up in northern Corsica, in the Italian Alps. 9:39: Ken asks about her transition back to the United States, where she attended John Hopkins University after spending 3 years in France. 10:23: Ken mentions Marie’s reputation at John Hopkins for being a “desert rat” in Utah’s Henry mountains. He asks her to elaborate on her experiences in that area. 12:06: Dawn comments on how after Marie got her PhD in 1987, she went to work for the U.S. Geological Survey, and that she ended up doing a structural study of the seismically active Kaoiki fault zone on the southeast flank of the Mauna Loa Volcano in Hawaii. Dawn asks Marie to talk about that. 13:44: Dawn comments on how Marie didn’t know much about Rome until she spent a year there in 1995. Marie talks about her experience. 14:17: Ken mentions that Marie’s priority for many years was to raise her children, but Ken asks what else she did in those days. 15:05: Dawn comments on how during this period, Marie was writing papers and working with scientists who were nearing retirement.  Dawn asks what that was like. 17:55: Dawn asks about the work Marie did after she started, in 2011, working at UC Berkley’s Department of Civil and Environmental Engineering as a project scientist. 19:55: Ken mentions that after a couple of years at Berkley, Marie accepted a position at the University of Utah. He comments on how that must have been an interesting transition to come full circle back to Utah. 20:44: Dawn asks for Marie to explain exactly how the Romans made concrete, and what made it so unique. 22:11: Ken mentions that while modern maritime concrete structures typically degrade significantly within a matter of decades, the Romans built piers and breakwaters 2,000 years ago that endure to this very day. He inquires as to what prevents Roman maritime concrete from degrading. 26:42: Ken comments on how the Romans are often said to be very deliberative people. He asks how much of the invention of their concrete does Marie think was deliberate, and how much a happy accident. 28:51: Ken asks about a comment that Pliny the Elder made in the first century about how the best maritime concrete was made from volcanic ash found in the regions along the Gulf of Naples. Ken asks Marie what is so particularly special about the ash at that particular region. 31:24: Ken mentions the Romacons project, and the book that came out of it, “Building for Eternity,” which was published in 2014. Marie is one of the authors, and the book explains how the Romans built these lasting structures in the sea. He asks if Marie could elaborate on the story the book tells. 35:14: Dawn asks Marie what the cementing characteristics are that have made Roman concrete so unique. 37:23: Ken mentions the demonstrated durability and longevity of Roman maritime concrete. He asks if lessons learned from the Romans could be of relevance to engineers currently working on devising containment for long term storage of hazardous waste substances. 41:11: Marie talks about her current project as the lead principle investigator on the Surtsey Volcano. 44:48: Dawn asks how Marie is disseminating the knowledge and information about the work that she and her team are doing at Surtsey. 46:20: Dawn asks Marie what life and career advice she would give to an up and coming scientist. 47:11: Ken inquires as to what Marie enjoys doing in her time away from research. 48:31: Interview ends.

Nearly five million people in the United States have Alzheimer’s disease. In 30 years, that number is estimated to be 16 million In today’s episode, Ken and Dawn interview Dr. Stephen Cunnane, a Canadian physiologist whose extensive research into Alzheimer’s disease is showing how ketones can be used as part of a prevention approach that helps delay or slow down the onset of Alzheimer’s. Cunnane is a metabolic physiologist at the University of Sherbrooke in Sherbrooke, Quebec. He is the author of five books, including” Survival of the Fattest: The Key to Human Brain Evolution,” which was published in 2005, and “Human Brain Evolution: Influence of Fresh and Coastal Food Resources,” which was published in 2010. He earned his Ph.D. in Physiology at McGill University in 1980 and did post-doctoral research on nutrition and brain development in Aberdeen, Scotland, London, and Nova Scotia. From 1986 to 2003, he was a faculty member in the Department of Nutritional Sciences at the University of Toronto where his research focused on the role of omega-3 fatty acids in brain development and human health. He also did research on the relation between ketones and a high-fat ketogenic diet on brain development. In 2003, Dr. Cunnane was awarded a senior Canada Research Chair at the Research Center on Aging and became a full professor at the University of Sherbrooke. He has published more than 280 peer-reviewed research papers and was elected to the French National Academy of Medicine in 2009. Links: Lower Brain 18F-Fluorodeoxyglucose Uptake: Castellano et al AD dPET J Alz Dis 2015 Brain glucose and acetoacetate metabolism: Nugent et al dPET YE Neurobiol Aging 2014 Energetic and nutritional constraints on infant brain development: Cunnane & Crawford J Human Evol 2014 Inverse relationship between brain glucose and ketone metabolism in adults: Courchesne-Loyer et al PET KD JCBFM 2016 A cross-sectional comparison of brain glucose and ketone metabolism in cognitively healthy older adults: Croteau et al. AD MCI CMR Exper Gerontol 2017 A 3-Month Aerobic Training Program Improves Brain Energy Metabolism in Mild Alzheimer’s Disease: Castellano et al. exercise ketones JAD 2017 Show notes: 3:33: Dawn mentions that Stephen was born in London but that his family emigrated to Canada when he was an infant. She asks him about growing up in a suburb of Montreal. 4:02: Ken mentions that he has been told by a reliable source that as soon as Stephen got into high school he spent a lot of time in the chemistry lab, where sometimes created mischief. 4:58: Dawn asks if it is true that Stephen nearly flunked out of college when he first started. 5:16: Dawn comments that Stephen got his PHD in physiology at McGill University which is when his interest in science really caught on and asks how that came about. 5:55: Stephen talks about communicating with Desmond Morris while Stephen was working on his post-doc. 8:03: Dawn asks about Stephen’s post-doctoral research, for which he traveled to Aberdeen London and Nova Scotia; as well as what prompted his interest in nutrition in the brain. 9:01: Dawn mentions that in 1986 Stephen became a faculty member in the department of nutritional sciences at the University of Toronto. She asks how he ended up teaching nutrition when he didn’t have a degree in nutrition. 10:33: Stephen talks about accepting a senior Canada Research Chair at the Research Center of Aging and a full professorship at the University of Sherbrooke. 11:57: Ken talks about Stephen’s interest in human evolution how it eventually led him to research the nutritional importance of shore-based foods and omega-3 fatty acid in particular in the development of human’s brains. He asks Stephen to talk about his work leading up to the hypothesis that humans evolved near the water. 16:32: Dawn asks which of the various forms and sources of omega-3 are optimal for overall wellness and brain health, and what are the differences between them. 18:50: Dawn asks Stephen if there was any pushback against his research into the importance of ketones and fat in the brain development of infants? Dawn points out that Stephen was working on this during the middle of the low-fat craze in the U.S. and Canada. 20:33: Dawn mentions that there is evidence that intermittent fasting improves cognition, and asks if there is any evolutionary basis for that? 21:49: Dawn asks if it was Stephen’s research into the metabolism of omega-3 fatty acids and the importance of ketones that lead him to write his book Survival of the Fattest? 23:04: Dawn notes that it seems as if ketones are at the core of Stephen’s way of thinking about infant brain development. She asks him to elaborate on this. 24:15: Dawn asks Stephen to talk about what it’s going to take to transition to the therapeutic use of ketones. 26:06: Ken mentions how Stephen has noted the importance of ketosis in postnatal life for a number of reasons, including brain development and survival and early breast milk availability. Ken asks about the effect of women consuming a ketogenic diet while breastfeeding children, and if this inadvertently lowers ketone levels in the infant due to lower medium chain triglyceride (MCT) levels in the breast milk, a phenomenon found in rodents fed a ketogenic diet during lactation. 28:36: Dawn comments how Stephen has said that certain brain-selective nutrients — such as DHA, iodine, iron, selenium, zinc and copper — would be best supplied by a shore-based diet. She asks which shores humans would have evolved close to and which types of food made up this diet during human evolution? 32:29: Dawn mentions that at Sherbrooke, Stephen’s research has been focused on the use of brain imaging techniques to study changing brain fuel metabolism and cognitive function during aging. She asks if he can give an overview of what he is finding. 34:08: Dawn comments on the increasing interest in exogenous ketones for treatment of neurological disease. She further mentions that these ketone esters can elevate Beta-hydroxybutyrate (BHB) levels far beyond what is normally attained during the ketogenic diet. She asks Stephen for his thoughts on the initiation of ketosis through MCTs versus exogenous ketones (salts or esters) versus carbohydrate restriction versus fasting. She asks about mechanistic differences between each of these methods of initiating ketosis. 35:39: Ken mentions that Stephen’s tracer work has used 11c acetoacetate in the setting of endogenous ketones and neurological disease. He asks if there are any key differences in brain ketone metabolism between endogenous and exogenesis ketosis after mentioning how BHB and acetoacetate appear in a relatively predictable 1:1 ratio when ketosis is induced through diet. 37:28: Ken mentions that it has been noted that ketones are 10% more efficient than glucose as a brain fuel. He asks Stephen about his understanding of cerebral fuel selection given ample availability of both glucose and ketones. 38:25: Dawn asks if there are areas of the brain that are particularly high users of ketone bodies, and if so, could that have any link to some of the functional or behavioral changes, such as mood, that are seen in some cases of animals or people adhering to a ketogenic diet. 39:16: Dawn asks Stephen to talk about his research into how and why omega-3 fatty acid homeostasis changes during aging. 40:21: Dawn asks for Stephen’s opinion on what are the primary challenges that our brains face as we age. 41:12: Dawn mentions how that Stephen is currently focused on Alzheimer’s research and ketones. She asks for an overview of his research that’s looking into how ketones can be used to the advantage of a person suffering from Alzheimer’s disease. 43:21: Dawn comments on how we know that APOE4 carriers have an increased risk of development of late onset familial Alzheimer’s disease. She asks if there is a link between the genotype and a change in brain metabolism. 44:42: Ken asks if substrate utilization differs between healthy subjects and those with neurological conditions, such as mild cognitive impairment or Alzheimer’s disease. 45:18: Dawn asks Stephen what other metabolic interventions he thinks have promise for a neurodegenerative disease. 46:01: Dawn mentions that exercise helps to get more ketones into the brain. She inquires as to how much exercise is needed to do this effectively. 46:49: Dawn asks Stephen to elaborate on his recommendation that older people who might not be able to exercise effectively should consider consuming a ketone drink made from MCTs that people can make in their kitchen. 48:31: Ken comments how he envisions it not being too long before studies can be done with powerful ketone ester drinks, and that exogenous ketones will become more readily available and more potent, giving people more effective options to elevate their level of circulating ketones. 50:09: Dawn asks Stephen if chronically high systemic inflammations contribute to neuroinflammation and cognitive decline. She also asks if targeting systemic inflammation with nutritional ketosis would be an acceptable strategy to enhance and also preserve cognitive function and brain longevity. 51:15: Dawn mentions that we know ketones increase brain blood flow and metabolism. She goes on to ask if Stephen thinks that some of the beneficial effects might be working through the newly discovered brain lymphatic system or glymphatic system. 51:41: Dawn points out there are about five million people with Alzheimer’s disease in the U.S., and that the number of Americans with AD is estimated to swell to 16 million in the next 30 years. She asks if Stephen thinks this dramatic increase in the prevalence of Alzheimer’s is related to the Western diet which has created an epidemic of type-2 diabetes and other chronic diseases. 52:42: Ken mentions that a number of recent papers show dramatic improvements in both health span and life span of rodents that are fed a ketogenic diet. While humans are not rats, he asks Stephen for his thoughts on the effects of prolonged ketosis as a promoter of human healthspan and perhaps even longevity. 53:51: Dawn concludes the interview by asking Stephen’s about his interests outside of work.

Today’s episode features one of the nation’s leading physicians and researchers who has spent years studying and treating traumatic brain injuries. Dr. Flora Hammond is a professor and chair of the Department of Physical Medicine and Rehabilitation at Indiana University School of Medicine. She also is the Chief of Medical Affairs and Medical Director at the Rehabilitation Hospital of Indiana. She has been a project director for the Traumatic Brain Injury Model System since 1998. Shortly before we conducted this interview with Dr. Hammond, she and a team of physicians and scientists at Indiana University received a $2.1 million grant to continue research into people who suffer traumatic brain injuries and how these injuries affect the lives of patients as well as their families. Dr. Hammond is a Pensacola, Florida, native who graduated from the Tulane University School of Medicine in 1990 and completed her residency in Physical Medicine and Rehabilitation at the Baylor College of Medicine in Houston. She also completed a brain injury medicine fellowship at Wayne State University School of Medicine in Detroit. Her research in the area of brain injury includes studying the prediction of outcome, aging with brain injury, causes of and treatments for irritability, and quality of relationships. In 2016 she received the Robert L. Moody Prize, which is the nation’s highest honor reserved for individuals who had made exceptional and sustained contributions to the lives of individuals with brain injuries. Prior to the 2016 Robert L. Moody Prize, Dr. Hammond received local and national awards for her teaching, clinical care and research, including the 2001 Association of Academic Physiatrists Young Academician Award, the 2011 Brain Injury Association of America William Caveness Award, and the 2013 Baylor College of Medicine Distinguished Alumnus Award. In 2011, 2012, and 2013, Dr. Hammond led the Galveston Brain Injury Conferences which focused on changing the view of brain injury as an incident with limited short-term treatment to a chronic condition that must be proactively managed over the course of life. She co-chairs the American Congress of Rehabilitation Medicine Chronic Brain Injury Task Force, and serves on Journal of Head Trauma Rehabilitation editorial board. She has authored more than 140 peer-reviewed publications. Links: Flora Hamond faculty profile: https://medicine.iu.edu/faculty/20302/hammond-flora/ “Potential Impact of Amantadine on Aggression” study https://www.ncbi.nlm.nih.gov/pubmed/28891908 Show notes: 4:08: Interview begins. 4:38: Dawn says it’s her understanding that Flora dreamed of becoming a physician ever since middle school. Dawn asks what inspired her at such an early age to become a doctor. 5:02: Flora talks about also wanting to become a teacher, but worried that she would have to give up teaching to become a doctor. 5:40: Continuing with Flora’s history, Dawn mentions that after high school Flora traveled to New Orleans to attend Tulane University. Dawn asks if it’s true that Flora’s grandmother was her landlord while she was in college and med school. 6:20: Ken mentions that Flora’s mother was a dietician and that her father was a pathologist. He asks Flora what specifically inspired her to specialize in brain injury rehabilitation and research. 8:36: Dawn comments on how before Flora accepted a positon at Indiana, she was in the Carolinas, and asks about her work there. 9:30: Dawn asks how Flora ended up at the Indiana University School of Medicine. 10:23: Ken mentions that Flora’s lecture at IHMC attracted a lot of interest and a full-house. He follows up by asking Flora what she thinks is driving the interest in brain injuries. 11:34: Dawn talks about how Flora and a team of physicians and scientists at Indiana have spent years studying and treating TBI (Traumatic Brain Injury) and the effects of TBI on the lives of patients and their families. She goes on to mention that Indiana recently was awarded a $2.1 million grant to continue those studies for the next five years. Dawns asks Flora to talk about the scope of the work she will be doing as a result of the grant. 12:57: Ken mentions that Flora has pushed to have a national approach to the treatment of TBI, where patients and physicians continuously track the injury and continue treatments. He asks her to expand on her thoughts on such a program and how more people and organizations can start working toward an integrated approach. 13:48: Dawn asks for Flora to explain the different types of brain injury, and to clarify that TBI is not merely one singular disease or type of injury process.  Flora goes on to explain the difference between mild, moderate and severe injuries, and then describes how the treatments differ. 14:50: Dawn asks Flora how she diagnoses the severity of TBI, and if there are any biomarkers that are currently in use. 16:01: Dawn asks what common issues patients struggle with after a traumatic brain injury. 17:08: Dawn proposes the hypothetical scenario of a patient coming into Flora’s rehabilitation clinic, and asks Flora to walk us through an example of how they would treat that person and what program they would go through. 19:21: Ken mentions that there are a number of TBI centers that focus on integrative medicine, and rather than just treating the brain injury they are now treating the patient as a whole human being. He talks about optimizing sleep, proper nutrition, and ways to manage aggression and anxiety in addition to specific treatment of the brain. He asks Flora how much does it seem that physicians are currently integrating these approaches into TBI treatment around the country. 20:17: Dawn asks what we know about the triggers of irritability and aggression in TBI patients, and if there is a biochemical component to these triggers or if it is something else. 22:21: Dawn inquires as to the different ways that Flora uses to track a patient’s condition on the cognitive or emotional level. 22:45: Flora talks about research on aging after TBI, and that interestingly enough, it’s not always about worsened outcomes. Some people actually get better over time, while others stay the same or their condition even worsens over time. Dawn asks if there are ways to differentiate who will improve and who will worsen with time. 23:50: Ken comments on how in the past it was thought that brain plasticity, and thereby recovery, was more plausible for a child with TBI, but that recovery would plateau at some point. He points out, however, that much of Flora’s work has shown that recovery can occur in older individuals and they can continue to improve long after the initial injury. He asks Flora if she could talk about that work. 24:44: Dawn asks if there is a difference in treatment for a child with TBI compared to an adult with a similar injury. 25:17: Ken mentions that ApoE 4/4, and even 3/4 status, has been shown to be a genotype that is associated with worsened patient outcomes after TBI, and that there are other genetic variables beyond ApoE that are relevant. He asks, in regards to the era of precision medicine, are we looking at these genetic variables with respect to a personalized patient treatment program? 26:21: Ken asks if we are able to accurately predict outcomes in the early hours and days following the injury. 27:00: Dawn asks if a severe brain injury typically implies a poorer outcome. 27:36: Mentioning that she has several people close to her with various types of TBI, Dawn talks about how she loves the idea of a participatory research system that Flora has proposed and implemented. Dawn asks Flora to expand on this approach to TBI research. 28:31: Ken talks about how Flora has focused a lot of her research on non-pharmacological interventions for TBI. He asks for some examples of approaches that she has studied, and if those approaches are being harnessed by the general TBI treatment community. 29:33: Ken mentions that Flora recently published a study on the promising ability of the drug Amantadine to curb aggression in TBI patients. He asks if she could elaborate on that. 33:27: Dawn comments on how in most treatment modalities for brain injury, the focus is on the acute phase. She asks how can treatment be extended after the initial management, and what else does Flora think long-term treatments for TBI patients should include. 34:13: Dawn asks if it is true that all of the recovery from a brain injury happens within the first year. 35:08: Dawn asks if medication in the early recovery phase has a downside in the long term. 36:01: Ken mentions that a number of therapies for TBI that showed great promise in animal studies, failed to yield the hoped-for results in human trials. He asks what are the current barriers to developing new acute therapies that reduce morbidity and mortality in TBI patients are. 37:09: Ken comments on how TBI is an injury to the brain, but it also affects a variety of other systems and pathways in the body. He mentions that the Hypothalamic Pituitary Adrenal access can often be impacted in TBI patients. He asks for a brief explanation of the HP access and how damage to it can affect the patient. 38:38: Ken asks if there would ever be a case where a person with HPA access as their dysfunction could be misdiagnosed with TBI and vice versa? 39:24: Dawn mentions that it seems as though the HPA axis  has been widely ignored, comparatively speaking, to other metrics in TBI patients. She asks if we are starting to include its assessment and status in patients, as far as tracking is concerned. 39:52: Dawn comments on how Flora has coined the term CBI (Chronic Brain Injury). Dawn asks if CBI has been incorporated into a public health and societal approach, in addition to traditional medicine. 40:37: Ken asks Flora to elaborate on how she would scope and define CBI as opposed to TBI. 41:17: Dawn asks for Flora to talk about how brain injury rehab has evolved over her career. 42:21: Dawn congratulates Flora on receiving the Robert L. Moody Prize last year, which is the nation’s highest honor for individuals who have made exceptional and sustained contributions to the lives of people with brain injuries. She follows up by asking for some background on the award itself. 42:48: Dawn asks where Flora sees the field of TBI research and rehabilitation heading in the next 10 years. 43:48: Dawn closes by asking Flora how she likes to spend her free time.

Today’s interview features Dr. Lauren Jackson, a nationally known expert in the field of tumor and normal-tissue radiobiology. She is especially recognized for her expertise in medical countermeasure development for acute radiation sickness and delayed effects of acute radiation exposure. Lauren is the deputy director of the Division of Translational Radiation Sciences within the Department of Radiation Oncology at the University of Maryland School of Medicine. Lauren, who also goes by Isabel, received her bachelors in science in microbiology from North Carolina State University in 2006, and her PhD in pathology from Duke University in 2012. She currently is a principal or collaborating investigator on a number of industry and federally sponsored contracts and research grants. She has published extensively on the characterization and refinement of animal models of radiation-induced normal tissue injury that recapitulate the response in humans. Models developed in Lauren’s laboratory have gone on to receive FDA concurrence as appropriate for use in medical countermeasure screens. Lauren is a senior associate editor for Advances in Radiation Oncology, a journal of the American Society of Therapeutic Radiation Oncology, and serves as an ad hoc reviewer for several peer-reviewed journals. She also is the author of several book chapters on normal tissue tolerance to radiation, mechanisms of injury, and potential therapeutic interventions. Links: Jackson’s University of Maryland web page: http://www.medschool.umaryland.edu/profiles/Jackson-Isabel/ Radiation Emergency Medical Management website: https://www.remm.nlm.gov Centers for Disease Control website: https://www.emergency.cdc.gov/radiation/index.asp BARDA website: https://www.phe.gov/about/BARDA/Pages/default.aspx NIAID website: https://www.niaid.nih.gov Show notes: 5:06: Dawn begins interview by asking Lauren about her childhood and if it’s true that she was one of those children who was always asking questions? 5:39: Lauren talks about how she was more interested in history and the humanities in high school and wanted nothing to do with science. 5:59: Dawn asks Lauren about her decision to attend the University of Georgia to major in journalism and political science. 6:28: Ken comments on how even though Lauren was just 18 at the time, she was one of two students picked to represent the University of Georgia at the Center for the Presidency in Washington, D.C. Lauren then talks about how thanks to that experience, she decided journalism and political science weren’t the right majors for her. 7:38: Dawn points out that when Lauren first went to college, she took the minimum number of science classes.  Lauren goes on to talk about how after spending time in D.C., she ended up applying to North Carolina State University and switching her major to microbiology. 8:52: While at N.C. State, Lauren worked for Dr. Hosni Hassan, an expert on Oxidative Stress. Dawn asks Lauren about the focus of her research with Dr. Hassan. 9:58 Dawn talks about how when Lauren was an undergrad at N.C. State, she became interested in tumors and cancer treatment, and found a professor down the road at Duke University who was doing interesting work in that area. Dawn asks Lauren if that’s why she ended up going to Duke for her doctorate. 10:52 Dawn asks Lauren to elaborate on how her background in journalism and political science connected her towards the path of radiation countermeasure research.  11:42 Dawn points out that as a graduate student at Duke, Lauren took part in projects that looked at radiation injury. Dawn asks Lauren to give an overview of what sort of work was involved in the projects.  12:46 Ken asks Lauren to explain the difference between clinical radiation exposure and radiation that someone would experience as a consequence of a nuclear attack. 13:59: Ken shifts the conversation to human space flight, asking Lauren to discuss the radiation astronauts will experience outside the protection of the Earth’s magnetosphere, such as galactic cosmic radiation and solar particle events. He also asks how they relate to the other previously mentioned clinical- and weapons-based radiation. 14:52: Ken asks Lauren to describe what the lifetime limits are for radiation exposure, how they are produced, and what is the biggest source of radiation exposure for the average person. 16:06: Dawn asks if it’s possible to translate the findings in clinical radiation to these other types of radiation exposures, such as nuclear weapons and space radiation. 16:40: Dawn asks if clinical radiation research is playing a role in the work that’s being done in space research as well as research into the effects of nuclear-weapons attack. 17:27: Ken asks Lauren to explain how radiation doses are defined. 18:28: Ken mentions that Lauren’s work has focused on both the acute and chronic effects of radiation exposure, then asks her to give an overview on how the body would respond at the cellular and physiological levels to an acute exposure. 19:56: Dawn mentions how proximity to the event, in the event of a nuclear attack, would be a variable factor as to the level of exposure, then asking what else determines the degree of an acute response. 22:35: Dawn asks if the impact of radiation exposure is different based on different systems in the body, further asking which systems are more or less susceptible and what the different responses are. 24:06: Dawn mentions how Lauren has focused a large part of her research on the effects of radiation exposure to the pulmonary system, then asking her to talk about those chronic and lifetime affects following initial exposure. 25:38: Ken remarks how oxidative stress is a major focus on Lauren’s research, and follows up by asking about the impact of oxidative stress on the tissue, surrounding tissue, and its role in the overall injury response. 26:54: Ken remarks on the evidence that shows that animals fed a diet high in blueberries have some degree of resistance to the inflammatory response due to the blueberry’s antioxidant activity. He asks if antioxidants, more broadly, could play a role in the prevention of radiation injury. 27:46: Dawn asks about genetic susceptibility to radiation injury, and if we know of any individuals who are more or less susceptible to injury based on their genetic makeup. 28:48: Ken wonders if the genetic screening for radiation tolerance were developed adequately, that perhaps it could have an application in the selection process for long-duration missions into deep space. 29:25: Ken inquiries about the counterintuitive fact that smokers have a reduced incidence of radiation-induced lung cancer. 30:07: Dawn asks if gender or age play a role in a person’s susceptibility to radiation injury. 31:13: Dawn mentions how we know that epigenetic modifications (changes with respect to how a gene is expressed) can occur in response to a wide variety of different stressors or environmental influences. She then asks if we are seeing modifications that occur as a result of radiation exposure at the epigenetic level. 31:47: Dawn mentions that Randy Gerald was at Duke at the same time that she and Lauren were at Duke, and that he was the founder of epigenetic modifications. 32:15: Ken asks that in regards to a point-of-care test that could identify individuals who have been exposed to radiation and injured, what are the potential markers that Lauren would look for. 34:01: Dawn asks if markers of tissue injury, such as lung-radiation injury, are found in the blood. 35:44 Ken mentions the importance of timing from the point of injury as being critical with most biomarkers. He then asks that given the temporal nature of radiation injury, is there a time effect on biomarkers of radiation injury. 36:37: Ken asks about the effects of radon. 37:30: Ken notes that some areas are inherently much higher in radon levels than others, such as New England, and parts of Florida. He asks if there is a level that Lauren would consider safe for basements. 38:42: Dawn asks about the current position Lauren holds at the University of Maryland School of Medicine as the Deputy Director of the Division of Translational Research Sciences, and the Department of Radiation Oncology, and her research team that she has there. 40:32: Dawn asks about the different categories of potential countermeasures for radiation injury that Lauren has been looking at. 41:28: Dawn mentions how Lauren also works alongside the FDA, where she serves as a subject-matter expert for the review committees. She asks Lauren to describe her work with the FDA and in particular the FDA animal rule and the role that plays in countermeasure approval for humans. 44:03: Lauren explains the role that the NIAID (National Institute for Allergy and Infectious Disease) plays in countermeasure development. 45:56: Ken asks if countermeasures that we might develop to limit the damage from a nuclear attack might potentially be used for applications such as clinical radiation or space radiation exposure. 47:12: Dawn asks about a countermeasure drug called Bio300 that Lauren worked on with a company called Humanetics Corporation, asking where it stands with respect to research and potential clinical applications in humans. 48:37: Dawn asks Lauren to talk about the approval process and the specifics of Neupogen and Neulasta, (the first two drugs ever approved as potential countermeasures for acute radiation syndrome) that were approved on the basis of data generated at Lauren’s laboratory. 49:58: Ken notes that Neupogen has demonstrated improved survival in people exposed to lethal radiation doses on Earth, then asks if Neupogen, Neulasta, or some other bone-marrow active medical countermeasures have applications in human space flight. 50:54: Dawn asks if there is a one-size-fits-all drug to target all the physiological systems in response to radiation exposure, or if a patient would need to take an array of countermeasures to cover each of the different systems. 52:22: Dawn notes that after Fukushima, potassium iodine pills were flying off the shelves, and asks if that is a viable option for protection against acute radiation syndrome. 53:32: Ken asks if there are any prophylactic treatments approved or in development for radiation exposure. 54:46: Ken asks Lauren to talk a little more about BARDA (Biomedical Advanced Research and Development Authority) and the role it plays in radiation injury research and countermeasure development. 56:44: Dawn notes that Lauren has served as the program director for the BARDA Radiological and Nuclear Model Development Program, asking her to talk about that position and what that work entails. 57:25: Lauren talks about how it seemed that no one was interested in radiation after the Cold War, but that recent interest in radiation research has grown significantly. 59:48: Dawn mentions that four or five years ago you couldn’t get any companies interested in looking at ways to improve survival in case of a nuclear attack, but that in just the last two weeks of November that Lauren has had 22 companies reach out to her. 1:01:48: Dawn asks what the current threats of nuclear or radiological terrorism or nuclear attack are. 1:02:18: Ken asks how much protection to radiation exposure, arising from a weapon’s detonation, does a basement offer. 1:03:05: Ken remarks how, in regards to basements, those that do not have windows would be preferable in the context of protecting against radiation exposure. 1:04:13: Ken asks if any of the countermeasures developed thus far could be effective against space radiation, and thereby offer NASA an ability to leverage the BARDA investment. 1:05:26: Ken remarks how he is glad to hear that the federal agencies are wisely leveraging each other’s investments, rather than independently pursuing them. 1:06:31: Ken talks about long-duration missions in deep space and the possibility that astronauts might experience serious cognitive deficits caused by radiation exposure. He also points out the need for a countermeasure against cognitive decline as a result of radiation is not yet met here on Earth, citing that workers who cleaned up the Chernobyl nuclear disaster experienced serious cognitive decline close to ten years after the incident. 1:08:22: Ken asks if potential neurocognitive medical countermeasures exist today or if they may be available in the near future, and would a single agent be effective for both terrestrial exposures and the galactic cosmic radiation found in space. 1:09:18: Dawn wraps up the interview by asking Lauren if she is an N.C. State fan or a Duke fan when it comes to basketball.

Today’s episode is the second of a two-part interview with IHMC Senior Scientist Dr. Jonathan Clark, a six-time Space Shuttle crew surgeon who has served in numerous roles for both NASA and the Navy. Part one of our interview, episode 55, ended with Jon talking about the tragic death of his wife, astronaut Laurel Clark. She died along with six fellow crew members in the Space Shuttle Columbia disaster in 2003. February marks the 15th anniversary of the disaster. Today’s episode picks up with Jon talking about becoming part of a NASA team that investigated the Columbia disaster. Ken and Dawn also talk to Jon about the extensive research he has been doing on the neurologic effects of extreme environments, and also about the instrumental work he has been doing in developing new protocols to benefit future aviators and astronauts. Jon received his Bachelor of Science from Texas A&M University, and medical degree from the Uniformed Services University of the Health Sciences in Bethesda, Maryland. He is board certified in neurology and aerospace medicine. Jon headed the Spatial Orientation Systems Department at the Naval Aerospace Medical Research Laboratory in Pensacola. He also held other top positions in the Navy and qualified as a Naval flight officer, Naval flight surgeon, Navy diver and Special Forces freefall parachutist. Jon’s service as a Space Shuttle crew surgeon was part of an eight-year tenure at NASA, where he was also chief of the Medical Operations Branch and an FAA senior aviation medical examiner for the NASA Johnson Space Center Flight Medicine Clinic. He additionally served as a Department of Defense Space Shuttle Support flight surgeon covering two shuttle missions. In addition to his new role as a senior research scientist at IHMC, Jon is an associate professor of Neurology and Space Medicine at Baylor College of Medicine and teaches operation space medicine at Baylor’s Center for Space Medicine. He also is the space medicine advisor for the National Space Biomedical Research Institute, and is a clinical assistant professor at the University of Texas Medical Branch in Galveston where he teaches at the Aerospace Medicine Residency. Links: Jon Clark’s NASA bio: https://www.nasa.gov/offices/nesc/academy/Clark-Jonathan-Bio.html Jon Clark You Tube Channel: https://www.youtube.com/playlist?list=PLZLZ5yKgXJR0L1xZzhdTY_dUzo5ZLILxS Jon Clark Red Bull Stratos page: http://www.redbullstratos.com/the-team/jonathan-clark/index.html Part one of Jon Clark STEM-Talk interview: http://www.ihmc.us/stemtalk/episode-55/ Show Notes: 4:07: Ken comments that Jon was part of the NASA team that studied every detail of the Columbia disaster. When the team’s report came out, Jon said, “You have to find ways to turn badness into goodness. You have to. It’s the only way you get through this.” Ken then asks Jon to talk about some of the lessons NASA learned. 7:27: Dawn says that on October 14, 2012, Jon was part of a team that successfully accomplished the highest stratospheric free fall jump from 128,100 feet. Dawn asks Jon how he became involved in this record-breaking jump. 9:37: Dawn asks Jon what his support team looked like for the jump. 11:15: Ken asks Jon what kind of preparation he and the team went through for the jump, and how long the preparatory period was. 12:46: Dawn asks Jon what the medical concerns for the jump were. 16:54 Dawn comments that when Jon discusses the medical team, he talks a lot about continuous physiological monitoring in the research world. She then asks Jon what kind of monitoring he was doing before, during, and after the jump. 22:58: Dawn asks Jon to discuss research he has done around neurological issues, specifically when it comes to space exposure. 23:31: Ken comments that intermittent artificial gravity has been discussed over the years, as a way to potentially mitigate some of the medical risk factors associated with long duration space missions. Ken then asks Jon how this may be accomplished in space and what we know about the effects of intermittent gravity. 30:30: Dawn says that NASA recently released a report describing an increased incidence of white matter hyper intensities in astronauts. She then asks Jon why we are seeing these lesions now and not in earlier crew. 34:01: Dawn comments that the DOD communities are also interested in the issue of white matter hyper intensities. Dawn then says that she and Jon are on a NASA Translational Research Institute project that is looking at the effect of simulated microgravity on brain lymphatic outflow. She then asks Jon to talk more about this study. 38:24: Dawn says that trying to perform effective aeromedical research with either aviators or astronauts can be difficult due to a fear of participating in studies whose findings might affect their flight status. She then asks Jon how he addresses these concerns. 41:02: Ken says that Jon has been extensively involved in previous investigations focused on physiological episodes in the aviation community. He then asks Jon to discuss what is meant by the term physiological episode and to give a few examples. 46:09: Dawn asks Jon what he sees as some of the most exciting areas of research for extreme environmental medicine in human performance. 48:42: Ken comments that Jon was instrumental in having EEG recordings removed from the standard flight physical. Ken asks Jon what led to his concerns on this measurement. 51:15: Dawn says that Jon has done research with hyperbaric oxygen and that right now we are seeing a push to bring hyperbaric oxygen therapy in as treatment for things like traumatic brain injury and PTSD. She then asks Jon what his thoughts are on this. 56:00: Dawn says that Jon has been extensively involved in suit testing for NASA and other commercial entities. She then asks what this testing involves and what the future space suits will look like. 1:00: 19:Ken says that there was a meeting at IHMC years ago where NASA displayed each of the generations of NASA space suits. 1:03:41: Dawn asks Jon to expand on his comments about how to get a deliverable from research. 1:05:05: Dawn says that William Fife was a key mentor of Jon’s and that now Jon works with William’s daughter. Dawn asks Jon to discuss the time he spends mentoring young students and what advice he has for them. 1:08:03: Ken says that NASA has been formulating plans for a crew tended cislunar space station concept, known as the Deep Space Gateway. This station could be used as a staging ground for robotic and human lunar surface missions as well as eventual travel to Mars. Ken then asks Jon to talk more about the Deep Space Gateway. 1:11:41: Dawn asks Jon to discuss his recent sailing expedition off the California coast. 1:15:27: Ken mentions that Jon participated in the National Outdoor Leadership School executive expedition that went into the Wind River Range of Wyoming.  Ken points out the Roger Smith, who was featured on episode 51 of STEM-Talk, and his wife Margaret Creel were longtime instructors at NOLS, and asks Jon for his thoughts about NOLS and the work it does. 1:19:20: Ken and Dawn thank Jon for joining them.  

Today’s episode is the first of two-part interview with IHMC Senior Scientist Dr. Jonathan Clark, a six-time Space Shuttle crew surgeon who has served in numerous roles for both NASA and the Navy. In a wide-ranging conversation with Ken and Dawn, Jon talks about his 26-year career in the Navy, his extensive research on the neurologic effects of extreme environments on humans, and the tragic death of his wife, astronaut Laurel Clark, who died along with six fellow crew members in the Space Shuttle Columbia disaster in 2003. Jon received his Bachelor of Science from Texas A&M University, and medical degree from the Uniformed Services University of the Health Sciences in Bethesda, Maryland. He is board certified in neurology and aerospace medicine. Jon headed the Spatial Orientation Systems Department at the Naval Aerospace Medical Research Laboratory in Pensacola. He also held other top positions in the Navy and qualified as a Naval flight officer, Naval flight surgeon, Navy diver and Special Forces freefall parachutist. Jon’s service as a Space Shuttle crew surgeon was part of an eight-year tenure at NASA, where he was also chief of the Medical Operations Branch and an FAA senior aviation medical examiner for the NASA Johnson Space Center Flight Medicine Clinic. He additionally served as a Department of Defense Space Shuttle Support flight surgeon covering two shuttle missions. In addition to his new role as a senior research scientist at IHMC, Jon is an associate professor of Neurology and Space Medicine at Baylor College of Medicine and teaches operation space medicine at Baylor’s Center for Space Medicine. He also is the space medicine advisor for the National Space Biomedical Research Institute, and is a clinical assistant professor at the University of Texas Medical Branch in Galveston where he teaches at the Aerospace Medicine Residency. Links: Jon Clark’s NASA bio: https://www.nasa.gov/offices/nesc/academy/Clark-Jonathan-Bio.html Jon Clark’s YouTube channel: https://www.youtube.com/playlist?list=PLZLZ5yKgXJR0L1xZzhdTY_dUzo5ZLILxS Show Notes: 4:32: Ken and Dawn welcome Jon to the show. 4:47: Dawn comments that Jon was the son of an army officer, and as a result, he grew up all over the world. Dawn then asks Jon what it was like to move so frequently to different army bases as a youth. 5:24: Dawn says that Jon is known as a fairly frugal person and asks him to tell the story of a piece of burnt toast in Germany that contributed to his frugality. 6:39: Ken asks Jon to share the story of how he learned how to fly planes in Germany as a teen-ager. 9:43: Dawn comments that Jon had aquariums in his bedroom as a child. She then asks Jon what drew him to marine biology. 13:53: Dawn asks why Jon chose Texas A&M for college after leaving Germany. 15:36: Jon talks about how he was accepted into medical school during his senior year of college, and how he was disappointed that the Navy sent him to flight school instead. 18:46: Ken says that after flight school, Jon ended up going to medical school after all. Ken asks Jon to talk about what happened. 20:09: Dawn asks Jon what it was like transitioning from being an officer in the Navy to a student in medical school. 21:24: Dawn comments that Jon was three years into his neurosurgery residency when his plans shifted. She asks Jon what happened. 24:52: Dawn says that Jon spent 26 years on active duty with the Navy, qualifying as a Naval Flight Officer, Naval Flight Surgeon, Navy Diver, U.S. Army Parachutist, and Special Forces Military Free Fall Parachutist. She asks Jon if it is fair to say that he has an appetite to try new things. 26:35: Ken comments that he and Jon met in Bruce Dunn’s lab at the University of West Florida in the late 1980s while Jon was in Pensacola working at the Naval Aerospace Medical Institute. Ken says that he recalls Jon working with Bruce on electrophysiology studies. Ken then asks Jon how he and Bruce met. 30:36: Ken says that Jon met his wife, Laurel, while he was in the Navy Dive School in Panama City. 35:34: STEM-TALK BLURB 36:00: Dawn asks Jon to share his experiences with the Marines in Desert Storm. 38:44 Dawn comments that Jon ended up back in Pensacola in the mid-1990s as the department head of the Naval Aerospace Medical Research Laboratory. During this time, Jon looked into the low-frequency active sonar, which was injuring both marine life and divers. Dawn then asks Jon to discuss this project. 41:14: Dawn asks Jon to discuss the Bug Springs project. 44:32: Ken comments that in 1996, Laurel was selected as a NASA astronaut, and she moved to Houston to begin astronaut candidate training. During this time, Jon was still in the Navy. Ken then asks Jon how he ended up working at NASA in Houston. 50:07: Ken asks Jon to discuss the transition at NASA. 53:02: Dawn asks Jon what his responsibilities were as a NASA flight surgeon. 55:00: Ken comments that it must have been an extremely tough experience when Laurel was aboard the space shuttle Columbia, that disintegrated upon reentering Earth in 2003. 1:00:40: Dawn comments that Jon’s son Ian asked why his mother did not bail out during the accident. Ian also told Jon that he was going to become a scientist and invent a time machine in order to go back in time and warn everyone. This was when Jon realized he had to focus the rest of his career on making it safe for those following in Laurel’s footsteps. 1:02:00: Part one of the interview ends.    

Late in 2017, a San Francisco startup company brought one of the commercial ketone esters to market. Today’s episode features an interview with a scientist and world-class athlete who has spent the past year helping develop and rollout HVMN Ketone, an FDA-approved drink that promises increased athletic ability as well as heightened focus and energy. Dr. Brianna Stubbs earned her PhD in biochemical physiology from Oxford University in 2016 where she researched the effects of ketone drinks on elite athletes. During Brianna’s collegiate athletic career, she won two gold medals while representing Great Britain at the World Rowing Championships. She first made international news when as a 12-year-old she became the youngest person ever to row across the British Channel. Brianna graduated from Oxford’s Pembroke College with a BA in preclinical sciences with the idea of becoming an MD.  But after spending a year working as a research assistant helping to investigate the effect of exogenous ketones on human performance, she decided instead to pursue her doctorate in biochemical physiology and investigate how ketone compounds might be applied in a sporting and healthcare setting in the future. While at Oxford, she worked alongside Dr. Kieran Clarke to develop a novel ketone monoester that has been shown to improve exercise performance in endurance athletes. She also was a member of the Great Britain Rowing Team and in 2016 become the World Champion in the lightweight guadruple sculls. Brianna’s time at Oxford gave her a unique opportunity to combine her scientific interest in sports physiology and metabolism while also competing at an international level. Brianna moved to the United States in June of 2017 to work at HVMN and help bring the company’s ketone ester to market. Links: HVMN website: https://hvmn.com/ketone Mark Mattson STEM-Talk: http://www.ihmc.us/stemtalk/episode007/ Wikipedia: https://www.youtube.com/watch?v=hNhuJ4JiK40 Mice and ketones cognition: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5102124/#!po=10.1064 Owen and Cahill: https://www.ncbi.nlm.nih.gov/pubmed/6061736 Oxford ketone study: https://www.ncbi.nlm.nih.gov/pubmed/27475046 Glycogen re-synthesi and ketones: https://www.ncbi.nlm.nih.gov/pubmed/28398950 Ketones, glycogen and mTOR: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440563/ Caryn Zinn: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5506682/ Ketone esters vs ketone salts: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5670148/ Acetoacetate paper:            https://www.frontiersin.org/articles/10.3389/fphys.2017.00806/full HVMN online fasting community: https://www.facebook.com/groups/136348456816447/ Show notes: 3:52: Ken and Dawn welcome Brianna to the show. 4:07: Dawn congratulates Brianna on bringing one of the first ketone esters to the commercial market, and asks Brianna to provide some background that led to the ketone ester launch. 5:31: Ken comments that the HBMN ester has been approved by the FDA as “generally recognized as safe,” or GRAS. He then asks her to expand on what this means in terms of human use and to expand on the value of the GRAS status. 6:31: Dawn asks Brianna what sparked her interest in science. 7:18: Ken comments that he heard Brianna was seven years old when she ran her first race, and that she ran so hard, she made herself sick. He asks if this is true. 8:16: Ken says that Brianna’s father was the one who got her interested in rowing, and when she was six years old, he signed her up for the first rowing race across the Atlantic Ocean. Ken asks if it’s true that he had never rowed before. 10:21: Dawn comments that Brianna used to run and row with her father as he trained for these races, and then when she was 12 years old she rowed across the English Channel, becoming the youngest person to ever do so. Dawn asks how this came about. 11:59: Dawn asks what Brianna’s mother was doing while she and her father were off rowing across the English Channel. 12:41: Dawn says that Brianna won her first international rowing event when she was 16, and then at 18 she won a silver medal at the junior world championships. She then asks Brianna’s to describe her training schedule as a teenager. 13:44: Ken asks Brianna what it feels like to be the best in the world at something after winning a gold medal in rowing at the 2013 and 2016 world championships. 16:32: Ken says that as a rower, Brianna mainly competed as a lightweight. He then asks what this meant in terms of preparing for competition from both a nutritional and training standpoint. 18:18: Dawn comments that the problems associated with excess training stress and inappropriate energy balance in female athletes were previously called the female athlete triad, but it has now been renamed relative energy deficiency in sport (RED-S). She then asks if Brianna experienced any physiological issues associated with competing as a lightweight athlete and if she saw this in any of her male colleagues. 20:35: Dawn asks Brianna if she has any thoughts on how coaches, nutritionists, and sports scientists could better support their athletes to prevent these issues. 22:39: Ken says that it was during this time, when Brianna was at Oxford, that there was a study being done on the effects of ketone esters on rowers. He then asks how Brianna became directly involved in the study. 23:51: Dawn asks why Brianna chose to postpone her medical school training to devote more time to researching ketones. 25:04: Dawn says that she understands that the CEO and a team from HVMN visited Oxford and that Brianna sort of invited herself to dinner and convinced them that they needed to hire her to roll out the ketone ester. She then asks if that is how Brianna ended up in San Francisco. 26:52: Dawn asks what Brianna’s first year in the states has been like. 27:40: Dawn says that a bottle of the ketone ester provides 25 grams of beta-hydroxybutyrate, one of the ketone bodies that the body naturally produces during a fast or period of starvation. She then asks Brianna what happens after someone consumes a bottle. 29:32: Ken asks Brianna if she has given any thought to possible consequences of supplementing with only beta-hydroxybutyrate. He then says that it has occurred to him that there might be a reason why the liver produces roughly equal amounts of acetoacetate and beta-hydroxybutyrate. 31:34: Ken says that looking back on the Cahill study, he can’t imagine proposing a study like that to an IRB now. 32:01: Dawn comments that the work Brianna was doing with Dr. Clark suggests that drinking ketones alongside a high-carb meal deliver a powerful performance boost. She then asks Brianna if the carbs are necessary to get the full performance boost of the supplement. 32:56: Ken says that state, where there is high carbohydrate availability and high ketones, does not seem like something that would naturally occur and asks if Brianna has any thoughts on this. 33:47: Ken says that you can imagine sparing the glycogen stores for when you really need them would be a great advantage in many sports, as most sports are both aerobic and anaerobic. 34:18: Dawn asks if ketone esters are best utilized as a training aid, as opposed to being acutely administered before an event. 36:03: Ken says that there is evidence that the HVMN ketone ester improves athletic performance. He then asks Brianna about its effects on cognitive performance. 37:10: Dawn asks Brianna to talk about some of the animal studies that are being conducted on ketone esters and their impact on physical and cognitive performance. 38:37: Dawn asks Brianna to explain the difference between ketone salts and ketone esters, and to also give an overview of what the advantages and disadvantages are for each. 41:56: Ken asks how Brianna envisions people using the ketone esters as part of their nutrition plan for a multi-day race. 42:55: Ken asks Brianna if there has been a study to look at the effects of chronic ketone ester administration on performance. 44:27: Dawn asks Brianna to discuss the study in cell metabolism that was published last year that looked at ketone metabolism in elite athletes. 47:15: Dawn asks how Brianna blinded people to which was the ester and which was not during these studies, since the ester tastes bitter. 48:57: Ken asks if it would be feasible to put the agents into capsules to avert the possible confounding effects of distinguishing the rather unique taste. 49:55:  Brianna believes there are important factors in running a successful and accurate sports science study. 53:00: Brianna discusses where ketones fit in the hierarchy of fuel selection during exercise. 55:53: Ken says that the terminology, ketone and ketone esters, are not synonymous, and asks Brianna to give an overview. 57:06: STEMTALK BLURB 57:31: Dawn asks Brianna if administration of ketone esters in the context of moderate carb intake overcomes the alleged problem of reduced PDH activity associated with ketogenic diets. She then asks Brianna if she has measured PDH activity. 58:06: Ken asks Brianna if you could, by use of the ester for an athlete that was in ketosis, have the best of both worlds. 1:00:07: Dawn says that ketone supplementation has a lot of potential to improve the performance of elite athletes. She then asks Brianna if weekend warriors or average recreational athletes can benefit from ketone supplementation. 1:01:21: Ken discusses a study recently conducted in Australia which reported that an acetoacetate diester slightly decreased performance in elite cyclists. 1:04:16: Ken comments that the authors’ speculated that the observed performance decrement was the result of elevated acetoacetate levels, which he noted, does not make sense.  He also noted that all of the study participants experienced GI distress which could easily have accounted for the performance decrement. 1:06:29: Dawn asks Brianna if she thinks this study will further confuse the topic of ketone supplementation. 1:07:37: Ken says that science and religion are two different things, and that particularly in nutrition science and topics related to nutrition, it is an emotional hot button, and people get all spun up about it. 1:08:54: Ken discusses again how many sports are a mixture of aerobic and anaerobic work. He then asks Brianna how athletes will use exogenous ketones in sports with varying degrees of intensity. 1:12:39: Ken comments that it is where the ketogenic diet will have the largest effect for the aging population, both in terms of general wellness and signaling effects, with respect to avoidance of sarcopenia. 1:12:51: Brianna talks about how athletes who are already on a ketogenic diet will use ketone esters. 1:13:47: Ken discusses the increase in BDNF after exercise and a study by Sleiman et al. that showed that HDACs inhibit the production of BDNF. Also, that beta-hydroxybutyrate inhibits HDACS, which would likely increase the production of BDNF. He then asks Brianna if she has any thoughts on whether exogenous ketone ester, such as the HVMN product, might also elevate BDNF. 1:16:00: Ken says that we know that the endogenous ketones have powerful signaling functions, but one of the most fascinating questions is about which of those the ketone ester will provide equivalent or better. 1:17:50: Ken says that it is possible to have high ketone elevations with the ketogenic diet, but it makes it difficult for the people doing the study. 1:22:41: Dawn says that it was noted in a recent paper from a group at UC Davis that ketones, and specifically beta-hydroxybutyrate, potentiated mTOR-1 signaling in skeletal muscle. She then asks Brianna if there is reason to believe this occurs in other tissues or organs of the body, where a potentiating mTOR might not be welcome. 1:23:20: Ken says that they found that it was tissue specific, so the level in the liver was not elevated in that study. 1:24:55: Brianna talks about the public’s response to the launch of the HVMN ketone ester, and gives a rundown of common questions people have been asking. 1:27:51: Brianna shares what her diet is like now that she has retired from competitive rowing. 1:30:42: Ken comments that Mark Mattson discussed intermittent fasting on STEM-Talk on an earlier episode. 1:31:13: Dawn comments that it seems as though most researchers also have a social media presence today, allowing people to collaborate more. She then asks Brianna if she is active on social media. 1:34:02: Ken and Dawn thank Brianna for the interview.