Dr. Euan Ashley, a pioneer in genomic sequencing, discusses the use of precision medicine to predict, prevent, and diagnose diseases. Topics include his work with genome sequencing, advances in technology making sequencing cost-effective, the transformation of healthcare with pathogenic labels, the Undiagnosed Disease Network, and the benefits of exercise. Euan is a professor of medicine and genetics at Stanford University and author of The Genome Odyssey.

Ken, Fellow of the Association for the Advancement of Artificial Intelligence, discusses topics such as the future of AI, chatbots, therapeutic ketosis, protein intake for healthy aging, the potential of kratom for pain relief, and the existence of extraterrestrial life in the next few decades.

Today we have climatologist Dr. Judith Curry, Professor Emerita of Earth and Atmospheric Sciences at the Georgia Institute of Technology. Judy also is president of the Climate Forecast Application Network and the host of the blog, Climate Etc, which you can find at JudithCurry.com. Judy’s blog provides  a forum for climate researchers, academics and technical experts from other fields as well as citizen scientists to discuss topics related to climate science and policy. Judy’s research interests include hurricanes, remote sensing, atmospheric modeling, polar climates, air-sea interactions, climate models, and the use of unmanned aerial vehicles for atmospheric research. She was a member of the National Research Council’s Climate Research Committee, and has published more than 180 scientific papers. Judy has become known in scientific circles as a contrarian for pointing out the uncertainties and deficiencies of climate modeling. In 2017, she resigned from her tenured position at Georgia Tech partly because of the poisonous nature of the scientific discussion around human-caused global warming. Our interview with Judy follows the release of her book “Climate Change and Uncertainty: Rethinking our Response.” The book provides a framework for understanding and rethinking the climate-change debate. The book also offers a new way to think about climate change and the risks we are facing as well as the way we go about responding to it. Show notes: [00:03:44] To start the interview, Morley asks Judy what she was like as a kid. [00:04:08] Morley says he understands that Judy’s interest in science had a lot to do with a geologist who came to speak to Judy and her fifth-grade classmates. [00:05:06] Morley asks if it is true that directly after that talk, Judy went to the bookstore and bought a geology picture book. [00:05:39] Judy talks about her undergraduate education at Northern Illinois University and why she decided to major in geography. [00:06:08] Morley asks about Judy’s brief time at Colorado State University, which lasted just one quarter. [00:06:45] Morley mentions that for Judy’s Ph.D. thesis at the University of Chicago, she decided to research the role of radiative transfer on arctic weather. Morley asks if her decision to study the arctic atmosphere and sea ice turned out to be fortuitous. [00:07:35] Ken brings up the media consensus of the ‘70s and ‘80s about how the Earth was headed toward a new ice age because of air pollution blocking the sun. Ken mentions that climate is an incredibly complex system. He wonders if it were irresponsible for the media to proclaim certainty on such topics as a new approaching ice age, which we now know didn’t happen.  Ken asks Judy to weigh in. [00:10:48] Morley asks about a 1997 arctic expedition that Judy and her colleagues went on called SHEBA, or Surface Heat Budget of the Arctic Ocean, which aimed to document feedback among the atmosphere, sea ice, and the ocean. Judy talks about how the expedition sought to address discrepancies between observations and climate models. [00:12:14] Ken explains that the hurricane season of 2004 was a pivotal time, with 14 named storms in the North Atlantic, nine of which became hurricanes. Ken asks Judy about the influence that hurricane season had on her. [00:14:21] Ken mentions that a hurricane paper Judy published in 2005 attracted a lot of attention, with numerous fellow climatologists as well as the media championing her analysis that showed a doubling of Category 4 and 5 hurricanes since 1970. Ken goes on to note, however, that there were also some scathing critiques of her paper, particularly with respect to the hurricane data that the analysis relied on. Ken asks Judy to talk about how she engaged with her critics and what transpired. [00:16:42] Morley asks Judy about how she became a vocal supporter of the IPCC and the concerns it was raising following the 2004 hurricane season. [00:18:02] Ken follows up and asks Judy if she still believes that the warming the Earth has experienced has caused a spike in intense hurricanes. [00:18:37] Ken asks Judy about the unauthorized release of emails from the Climactic Research Unit at the University of East Anglia, otherwise known as “climategate.” The emails showed that some researchers were manipulating data to make it seem that he earth was heating up dangerously. [00:20:45] Morley asks Judy to give a primer on climate modeling and how complex it is. [00:22:09] Morley mentions that in her book, “Climate Uncertainty and Risk: Rethinking Our Response,” Judy discusses several incontrovertible facts about global warming. Morley asks Judy to list them for the listeners. [00:22:50] Morley mentions that Judy argues in her book that these facts about climate change do not tell us much about the most consequential issues associated with climate change. Morley goes on to mention that Judy’s book highlights four key arguments in regards to global warming. Her first argument is that we do not definitively know to what extent CO2 and other human-caused emissions have dominated natural climate variability as the cause of recent warming. Morley asks Judy to elaborate on this. [00:23:49] Morley asks Judy to explain her second argument, which is that we don’t have a good handle on how much the climate can be expected to change over the course of the 21st Century. [00:24:41] Ken explains that Judy’s third argument is that there is not agreement on whether warming is actually dangerous, and that the notion of danger is based on societal values on which science has little to nothing to say. Ken asks Judy to talk about these claims. [00:26:00] Ken asks Judy about her final argument, which is that there is widespread disagreement about whether radically reducing emissions will improve human wellbeing in the 21st Century. [00:27:29] Morley explains that Judy pointed out many of these issues in 2013 during testimony she gave to a house committee after President Obama’s United Nations climate pledge. Judy argued at the time that the climate community had been working on building a scientific consensus on anthropogenic climate change for 20 years, and that she believed this consensus building process perhaps had the unintended consequence of oversimplifying the climate change problem and its solution. Morley asks Judy to expand on this. [00:30:41] Morley explains that Judy mentioned on NPR’s show “All Things Considered” that she takes multiple steps to reduce her carbon footprint. Morley asks when she decided to implement those steps and why. [00:31:51] Morley explains that Judy once said in an interview that even if we achieved net zero with our carbon footprint, we would barely notice. Morley goes on to say that people hold up the pre-industrial era as a “golden age” for the climate, and asks Judy what her thoughts are on this. [00:32:50] Ken asks Judy to elaborate on her stance that there is no climate change emergency. Ken mentions that Judy’s stance has led to her being labeled a contrarian and dissident climatologist. [00:34:21] Ken explains that Judy resigned from her tenured position in 2017 due to a variety of factors, including not knowing how to advise students and postdocs on how to navigate the “craziness of the field of climate science.” Ken asks if this was a difficult decision for Judy. [00:35:44] Morley explains that in a post about her resignation, Judy wrote: “Once you detach from the academic mindset, publishing on the internet makes much more sense, and the peer review you can get on a technical blog is much more extensive. But peer review is not really the point; provoking people to think in new ways about something is really the point. In other words, science is a process, rather than a collection of decreed ‘truths.’” Morley asks Judy to expand on this perspective. [00:37:31] Morley explains that there has been a lot of publicity regarding the recent extreme weather events over the past few years, with some climatologists arguing that these events are evidence that we are in the midst of an emergency. He asks Judy for her take. [00:39:04] Morley mentions that Judy frequently argues that policy makers haven’t thought through climate change. While climate change is real, and has negative impacts, Judy argues that common portrayals of a crisis are unfounded. Morley goes on to mention a 2020 paper by Bjorn Lomborg in which he points out that under scenarios set out under the IPPCC, human welfare is likely to increase by 450 percent by the end of the 21st Century. Lomborg estimates climate damages will modestly reduce this welfare increase to 434 percent. Morley explains that Judy’s argument is that policymakers could screw up this upward trajectory in welfare if they destroy our current energy infrastructure. He asks Judy to expand on this. [00:41:37] Ken asks Judy to talk about how transitioning to all wind and solar power would require a large expenditure of fossil fuel. [00:44:13] Morley asks if it is true that Judy believes that instead of trying to reach zero carbon emissions by 2025, or some other date, that we should invest in increasing our resilience to extreme weather events. [00:45:05] Morley pivots to talk about Judy’s book, “Climate Uncertainty and Risk” which Judy began writing in 2020. [00:45:58] Morley asks Judy when and why she started her blog “Climate Etc.,” and how it helped her in preparation for her book. [00:46:31] Ken explains that Judy’s book is very ambitious and sets out to show how the narrow and politicized framing of the climate debate has resulted in an oversimplification of both the scientific problem and its solutions. Ken asks if it is true that the book is not just about the climate debate but also, in more broad terms, about uncertainty and risk. [00:48:00] Morley asks Judy about the second part of her book, specifically the chapter titled “The Climate Change Uncertainty Monster,” which highlights the problems we face in terms of climate change. [00:49:03] Morley mentions that there is a section in Judy’s book titled “Emissions and Temperature Targets.” She begins the chapter with a quote from environmental scientist John Foley: “The first rule of climate chess is this: The board is bigger than we think, and includes more than fossil fuels.” Morley asks Judy what else the board includes. [00:49:41] Morley asks about a paper that Judy referenced towards the end of her book in laying out scenarios for a way forward with climate change, “Usable Climate Science Is Adaption Science,” in which Adam Sobel of Columbia University writes that in the present historical moment, the only climate science that is truly usable is that which is oriented toward adaptation. He argues that current policies and politics are so far removed from what we need to do to avert dangerous climate change that scientific uncertainty is not a limiting factor on mitigation. [00:51:32] Morley asks about another paper that Judy references in her book titled “Small Is Beautiful: Climate-Change Science as if People Mattered.” Written by Regina Rodrigues of Brazil’s Department of Meteorology and Theodore Shepherd of the University of Reading in the UK, it describes how there is a widely accepted gap between the production and use of climate information. The authors call for a break with traditional climate research and methodology, which at the moment seems to be very top-down driven. Morley asks Judy to talk about the proposal for a more bottom-up approach. [00:52:26] Ken pivots to ask Judy about the term “wicked science,” which she refers to in the last chapter of her book. The chapter is titled “Wicked Science for Wicked Times.” [00:53:58] Morley asks Judy how she spends her time now that she has resigned from Georgia Tech and academic life. Links: Judith Curry Wikhhipedia page Judith Curry website Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio      

Dr. Donald Layman, expert on dietary protein and amino acids, shares his research on muscle development, metabolic regulation, and its implications for obesity, diabetes, and cardiovascular disease. He discusses protein intake recommendations, the importance of discrete meals for muscle health, and the effects of high protein diet and exercise on weight loss and muscle preservation. Additionally, he talks about the challenges in understanding plant-based diets and the importance of essential amino acids.

Dr. Josh Hagen, Director of the Human Performance Collaborative at Ohio State University, discusses optimizing performance in athletes and warfighters. He talks about monitoring neuromuscular performance in the military, optimizing performance in firefighters, creating rule-based systems for data analysis, and using wearable devices to assess and improve cognitive and physical performance in athletes and warfighters.

Today we have the world’s foremost authority on kratom returning to STEM-Talk after five years to give us an update on his research. Shortly after his 2018 interview on episode 61,  Dr. Christopher McCurdy and his lab at the University of Florida received two major grants from the National Institute of Drug Abuse to investigate the medical efficacy of kratom and its alkaloids, which we discuss in today’s show. Mitragyna speciosa, or kratom, is an herbal leaf from a tropical evergreen tree in the coffee family.  It is native to Southeast Asia where it has been used in herbal medicine for hundreds of years. Kratom has become increasingly popular in the United States and throughout the world for recreational purposes. But kratom is also becoming recognized in the medical and research communities for its treatment for chronic pain as well as its potential to alleviate opioid withdrawal symptoms. For more than 25 years, McCurdy has studied the design, synthesis, and development of drugs to treat pain, anxiety, and substance-abuse disorders. For the past 15 years, Chris and his lab have turned a lot of their attention toward kratom and its chemical components to better understand its potential to treat a multitude of conditions. Chris is a professor in the Medicinal Chemistry Department in the College of Pharmacy at the University of Florida. He also is director of the of school’s Translational Drug Development Core and an Associate Dean for Faculty Development. Our interview with Chris comes on the heels of Florida passing the Kratom Consumer Protection Act, which mandates that kratom products sold in the state meet a high standard of product purity. In today’s interview, we talk to Chris about the protection act as well as: — The numerous studies he has been able to conduct thanks to his lab’s two grants from the National Institute of Drug Abuse. — The disparity between the traditional use of kratom and the new often highly concentrated manufactured products sold in the U.S. — His lab’s study examining the effects of lyophilized kratom tea and its ability to alleviate withdrawal symptoms of opioid-dependence. — The potential of kratom alkaloids to serve as treatment of various substance abuse disorders. — The benefits and risks associated with CBD usage. Show notes [00:03:21] Dawn opens the interview welcoming Chris back to STEM-Talk and mentions that his last appearance was episode 61 in 2018. Dawn explains that Chris has devoted much of his research to kratom, or Mitragyna speciosa, which is a traditional Southeast Asian medicine. It has been used by indigenous populations for centuries to increase endurance, enhance mood, treat pain, and mitigate opioid withdrawal symptoms. Dawn asks Chris to give a short overview of kratom and why it is attracting so much attention recently. [00:09:14] Ken mentions that at the time Chris first appeared on STEM-Talk, he was in the process of attracting funding to take a deep dive into kratom, which he has now secured from the National Institute of Drug Abuse. Ken asks Chris to give a general overview of the research they are conducting with this grant and what they are finding. [00:15:19] Dawn mentions that in Chris’s last interview on STEM-Talk, he mentioned that researching kratom was difficult due to a lack of standardization and asks if this has changed. [00:21:11] Ken asks about a Thai product that is a freeze-dried leaf, which is coming to the US market, and if this product is more like what is used in Southeast Asia as opposed to the ground leaf material available in the U.S. market. [00:24:29] Dawn mentions that in 2020, Chris and a colleague published an article in the journal Current Opinion in Psychiatry on the need to address the disparity between the traditional use of kratom and the new often highly concentrated manufactured products sold in the U.S. and other countries. Dawn asks Chris to talk about the points made in this article. [00:32:35] Ken follows up on the previous discussion asking how the alkaloid strength and combination may change not only due to the processing of the kratom leaf material, but also as a factor of time. [00:36:33] Dawn asks about a paper that Chris and his colleagues published  in the journal Addiction Biology, which reported on research conducted with rats and looked at two of the major psychoactive constituents of kratom: mitragynine and 7-hydroxymitragynine, with an eye toward understanding their potential therapeutic value as well as their abuse potential. [00:44:12] Ken mentions that in November of 2020, Chris and his team published an article reporting on research examining the effects of lyophilized kratom tea with an eye toward determining if kratom alleviated withdrawal symptoms of opioid-dependence. Ken asks about the findings of this study. [00:50:21] Ken asks Chris what the difference is between the lyophilized kratom tea and other preparations. [00:54:20] Dawn mentions an article that Chris published in January and was tagged by the International Association of Pain Management as its paper of the week. Dawn explains that the paper addressed the potential of kratom alkaloids to serve as treatment of various substance abuse disorders. These alkaloids may serve as a blueprint for the development of novel therapies to treat these disorders. Dawn asks Chris to summarize this paper and its findings. [00:58:51] Dawn shifts the conversation to talk about CBD and explains that the FDA has said that further research needs to be done to determine how much CBD can be consumed before harm is caused. Chris has gone on record saying that we need to balance consumer desire for CBD products with a regulatory framework to ensure safety. Dawn asks Chris about the benefits and risks associated with CBD usage. [01:07:19] Ken asks Chris about a recent bill signed into law called the Florida Kratom Consumer Protection Act, which mandates that kratom products sold in Florida meet a very high standard of product purity. It also establishes labeling requirements and limits sales to consumers aged 21 and older. Ken asks Chris to talk about this legislation and why he was in favor of it. [01:13:13] Dawn closes the interview mentioning that Chris has certainly had a lot on his plate over the past five years. She asks what he foresees for his research over the next five years. Links: Christopher McCurdy bio Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio  

Today we have Dr. Brian Cole, an orthopedic surgeon who specializes in cartilage restoration, orthobiologics, and advanced surgical techniques for the treatment of knee, elbow, and shoulder injuries. He is the team physician for the NBA’s Chicago Bulls and the co-team physician for the Chicago White Sox. He also is the host of the Sports Medicine Weekly Podcast. Brian practices orthopedic sports medicine at Midwest Orthopaedics. He also is a professor of Orthopaedics, Anatomy and Cell Biology at Rush University Medical Center in Chicago. He is Managing Partner of Midwest Orthopaedics and is the department’s Associate Chairman and the Section Head of the Cartilage Research and Restoration Center. In addition to this work, he also serves as the Chairman of Surgery at Rush Oak Park Hospital. In today’s interview, we talk to Brian about his cutting-edge research into ways to treat knee, shoulder, and elbow injuries.  Brian shares his novel approach to dealing with ACL tears, one of the most common sports injuries, and his investigations of methods to enhance the healing and recovery time following ACL reconstructions. He also talks about new advances in minimally invasive surgical techniques for many common injuries.  We have a particularly interesting conversation with Brian about exciting developments in the use of stem-cell treatments as well as the use of bone marrow aspirate to treat injuries. Show notes: [00:03:53] Marcas opens the interview mentioning that Brian was in the eighth grade when he fell in love with a popular sit-com from the 1970s,  “The Bob Newhart Show.” Marcas asks Brain what he loved about the show and what impact it had on him. [00:05:07] Brian enrolled in the University of Illinois after graduating from high school. Marcas asks Brian if knew he wanted to major in biology and psychology when he arrived on campus. [00:05:58] Ken mentions that after Brian’s undergrad, he travelled upstate to the University of Chicago, where he earned an MD and an MBA. Ken asks what led Brian to pursue both an MD and MBA. [00:09:52] Ken explains that after the University of Chicago, Brian moved to New York City for an orthopaedic research fellowship in metabolic bone disease at the Hospital for Special Surgery. Brian also decided to do his residency there as well. Ken asks how that came about. [00:11:31] Marcas mentions that after Brian finished his fellowship and residency, he went to the University of Pittsburgh for a sports medicine fellowship. Marcas asks what led Brian there and what drove his interest in sports medicine. [00:13:10] Marcas asks Brian about a fortuitous phone call he received when he was a fourth-year resident. [00:14:34] Ken explains that Midwest Orthopaedics is one of the nation’s most respected private orthopaedic practices.  Ken notes that through a partnership with Rush University Medical Center, Midwest has developed a national reputation as a leader in sports medicine; hip, knee, spine, and cartilage restoration; as well as shoulder care and pain management. Rush also is an academic medical center that includes a 671-bed hospital and is a center for basic and clinical research. Ken asks Brian to describe the scope of the work that goes on at Midwest and Rush. [00:17:20] Marcas comments that Brian is also the head team physician for the Chicago Bulls and the co-team physician for the Chicago White Sox, and asks Brian to describe some of the work that he does in that capacity. [00:20:09] Marcas explains that Brian treats a wide range of patients with injuries and pain, from athletes to non-athletes, and from children to senior citizens, and that he has performed more than 20,000 surgeries over the course of his career. Marcas asks Brian to give a sense of the patients he sees and what his average day at the office is like. [00:24:00] Ken points out that Brian is known for focusing on treating the patient and not the x-ray or MRI. Ken goes on to say that x-rays and MRIs often bog down both the practitioner and patient with too much information. Brian often refers to this overload as BARF and VOMIT. Ken asks Brian to explain what he means by BARF and VOMIT. [00:31:56] Marcas reflects that a few decades ago, the only way to help someone with the loss of cartilage in the knee was to surgically go into the knee and clean up the debris. Bone on bone pain makes it difficult to walk, get up and down in a chair, and climb stairs. Marcas asks Brian to explain the range of options available to patients today in this regard. [00:35:31] Ken mentions that in the past couple of decades, there have been numerous advancements in how to treat patients with shoulder, elbow, and knee injuries via non-surgical means, ranging from biochemical to pharmacological to diet and rehabilitation. Ken asks Brian to give an overview of these nonsurgical methods and the status of evidence supporting each. [00:39:08] Ken explains that weight loss is often an effective approach to reducing knee pain, and that for every pound a person loses, it leads to a five-to seven-pound reduction at the level of a person’s joints below their waist. Ken asks Brian to talk about the importance of this and how he and others in the practice discuss this with their patients. [00:43:06] Marcas explains that ACL tears often require surgery and are among the most common injuries for athletes and workers in physically demanding jobs, with approximately 500,000 ACL tears each year. Marcas asks Brian to give a sense of what happens to a person when they experience an ACL injury. [00:46:05] Marcas comments that according to the American Academy of Pediatrics, ACL tears have skyrocketed among 14- to 18-year-olds, increasing by 148 percent over the past 10 years. Marcas asks what is causing this increase. [00:48:28] Ken follows up on the previous question mentioning that there is a critical need to develop novel strategies to enhance ACL healing and accelerate recovery time after an ACL reconstruction. Ken goes on to mention that Brian has a study that was designed to assess the effect of bone marrow aspirate concentrate to reduce recovery time and asks about the findings of this study. [00:51:03] Marcas comments that in the late 1900s, cultured chondrocytes implanted beneath a periosteal patch were used as a treatment for chondral injuries. Animal studies had demonstrated hyaline-like repair. Along with encouraging early clinical results, this led to the widespread implementation of autologous chondrocyte implantation, or ACI, in the U.S. and Europe. Marcas goes on to say that many clinical studies supported the long-term efficacy and durability of ACI, but today, scientists are investigating alternative methods of enhancing the biological repair and the surgical technique using ACI. Marcas asks about Brian’s paper – titled  “Current Status of Autologous Chondrocyte Implantation” –that recently appeared in Sports Medicine Reports. [00:53:52] Ken asks Brian to discuss meniscal tears, which are the most common pathology of the knee, and one of the most common pathologies in sports medicine. Ken mentions that Brian coauthored an editorial in the Journal of Arthroscopic and Related Surgery that pointed out the most important first step in terms of treatment is determining whether the injury is an acute traumatic tear or a degenerative one. [00:56:11] Ken asks Brian about the use of bone marrow aspirate, or platelet-rich plasma, as a source of growth factors in progenitor cells in rotator cuff repair, a topic on which Brian has a paper coming out highlighting reductions in re-tear rates. [00:58:30] Marcas mentions that Brian has also been involved in a few biomechanics studies looking at fixation of soft tissue to bone and also fixation of soft tissue using sutures, and asks Brian to give a sense of why this work is important. [01:00:31] Marcas explains that current research on osteoarthritis and treatments for it are moving beyond the diseased joint, integrating other articular tissues, including synovium, fibrocartilage, and bone, as well as periarticular structures like muscles, tendons, and ligaments. Marcas asks how this model affects treatment plans. [01:03:43] Marcas explains that until recently, the impact of inflammation on OA pathogenesis was perhaps underappreciated, as OA was not considered an inflammatory disease. He goes on to explain that the field seems to have shifted in this thinking to now include effects of inflammation on periarticular tissues. Marcas asks Brian what his thoughts are on this. [01:08:05] Ken mentions that one of the more promising developments in the field is the use of stem-cell treatments of various kinds, and to this point Ken mentions that there are a number of different approaches. Ken asks Brian to talk about this and perhaps separate fact from fiction on the matter. [01:10:23] Ken asks about cultured stem cells, which are used in treatments for which thousands of Americans travel overseas for each year. Ken asks if there are studies that show increased efficacy in any of these methods. [01:11:29] Ken mentions that Brian also specializes in the treatment of glenohumeral arthritis, which is a degenerative joint disease affecting the shoulder, and is characterized by the degeneration or wearing away of the protective cartilage covering the ends of the bones in the joint. Ken asks Brian to explain what the standard of care is for this disease. [01:13:41] Marcas asks what the average lifespan of a modern shoulder replacement can be expected to be. [01:15:44] Ken asks how reverse shoulder replacement compares to anatomical shoulder replacement. [01:17:10] Ken asks about a 2019 study in the British Medical Journal that reported the risks associated with shoulder replacement surgery for arthritic conditions is much higher than previously thought. Ken explains that the study found that one in four men aged 55 to 59 were at risk of needing further revision surgery, and that the risk of serious adverse events like heart attacks and major blood clots within 90 days of surgery were much higher than previously estimated, particularly in people over 85 years of age. [01:21:29] Marcas closes the interview mentioning that Brian, in addition to his medical practice, is also in the podcast business, hosting a weekly show called “Sports Medicine Weekly Podcast with Dr. Brian Cole.” Marcas asks Brian to discuss the range of topics covered in the podcast.

Today we have our good friend and colleague Dr. Dominic D’Agostino returning for his third appearance on STEM-Talk. Dom, as most of our longtime listeners know, is well-known for his research into the ketogenic diet and the physiological benefits of nutritional ketosis. Since our last conversation with Dom in 2019, a tremendous body of research has been added to the literature about the therapeutic potential of ketosis. The high-fat, low-carb ketogenic diet has been linked to advances in the treatment of Alzheimer’s, cancer, migraines, type-2 diabetes, psoriasis, sleep apnea, psychiatric disorders, traumatic brain injuries as well as a host of other diseases and disorders, which we cover in today’s interview. In episode 14 of STEM-Talk, we talked to Dom about his development and testing of metabolic therapies involving the ketogenic diet for a wide range of diseases and conditions. In episode 87, Dom returned to reflect on his 10 years of research focused on the high-fat/low-carbohydrate diet. In today’s interview, we talk to Dom about this latest work as well as his extensive research on hyperbaric oxygen. Dom is a tenured Associate Professor in the Department of Molecular Pharmacology and Physiology at the University of South Florida Morsani. He specializes in neuroscience, molecular pharmacology, nutrition, and physiology. Dom also is our colleague and a research scientist here at the IHMC. Show notes  [00:02:50] Dawn opens the interview mentioning Dom’s recent IHMC Evening Lecture, in which he mentions the film “First Do No Harm” starring Meryl Streep. The film is based on the true story of a four-year-old boy diagnosed with severe epilepsy, whose extreme seizures continued despite extensive medical treatments. The boy’s mother reached to Dr. John Freeman, a physician who had successfully treated patients with a ketogenic diet. Dawn asks Dom to give some context about this fictional film based on a true story. [00:05:05] Dawn asks Dom to discuss the many evidence-based applications of the ketogenic diet that he highlighted in his IHMC evening lecture. [00:07:11] Ken asks Dom about another story involving Russell Winwood, a man with severe chronic obstructive pulmonary disease, also known as COPD. Russell reached out to Dom with respect to treating his COPD with a ketogenic diet. [00:11:21] Ken asks if Russell only engaged in the ketogenic diet or if also used exogenous ketones. [00:12:10] Ken mentions that the ketogenic diet has the broad potential to be an anti-inflammatory diet. Ken goes on to mention that COPD is an inflammatory disease. As Dom’s case report suggested, Ken wonders if the ketogenic diet has the potential to have strong therapeutic effects for other inflammatory conditions as well. Ken asks what other conditions Dom thinks might benefit from therapeutic ketosis. [00:14:02] Dawn mentions that Dom has been busy since his last appearance on STEM-Talk, having authored or collaborated on more than 40 papers, one of which garnered a lot of attention and was published in Frontiers in Neuroscience. This paper investigated whether therapeutic ketosis via ketone esters could represent a viable way to treat epilepsy and other seizure disorders. Dawn asks Dom to elaborate on this paper’s findings and their significance. [00:16:26] Ken mentions that those listeners who are unfamiliar with ketone esters may want to check out our interview with Dr. Brianna Stubbs. Ken asks Dom to give a quick primer on ketone esters and why so many researchers in the field are excited about their potential. [00:19:20] Ken mentions that in addition to ketone salts and ketone esters, there are other product formulations out now, like the one from a company called Kenetik. Ken asks Dom what he thinks about this formulation. [00:23:33] Dawn mentions that Dom has had a number of animal studies published since 2019 looking at ketone induced neuroprotection and asks Dom to give an overview of some of this work. [00:25:57] Dawn asks Dom about his research on Angelman Syndrome, which is a rare genetic and neurological disorder that causes seizures, developmental delay, loss of body movements, and lack of speech. Dawn mentions that Dom was a part of a mouse study that explored whether ketone supplementation could mimic the ketogenic diet as an anticonvulsant, as well as the effects of ketone esters on behavioral and metabolic outcomes. The results of this study were promising, and Dawn asks Dom to talk about some of the key takeaways. [00:29:37] Ken mentions that it makes sense that the ketogenic diet would elevate NAD (nicotinamide adenine dinucleotide) levels. Ken asks Dom whether this same effect is observed with exogenous ketones. [00:30:32] Ken mentions that in the last decade there have been numerous human studies that have investigated the therapeutic role of ketogenic diets in various neurological disorders, with recent work looking into the potential therapeutic effects of ketosis on Alzheimer’s disease. Ken asks Dom to touch on some of this research, and also mentions that episode 59 of STEM-Talk with Steven Cunnane focused a good bit on Alzheimer’s in the context of exogenous ketones. [00:35:02] Dawn mentions that Dom was part of two studies that examined the effects of a ketogenic diet on athletic performance. Dawn goes on to explain that high-carbohydrate, low-fat diets have been the standard for athletes for years, but recent research has challenged the superiority of carb loading. Dawn mentions that former IHMC colleague Dr. Andrew Koutnik published a study that had middle aged athletes undergo two different 31-day isocaloric diets, one which was high carb, and the other ketogenic. Dawn explains that both Dom and Jeff Volek participated in this study and asks Dom what the key takeaways were. [00:37:46] Ken explains that Dom and Jeff Volek also collaborated with Andrew Koutnik on another study on the crossover effect. Before diving into that study specifically, Ken asks Dom to explain what the crossover effect is. [00:40:13] Dawn mentions that Dom has been a part of many studies that have demonstrated the positive impact of a ketogenic diet, but addressing the elephant in the room, Dawn asks Dom what his thoughts are on the fact that some individuals respond to the ketogenic diet by developing a marked elevation of LDL cholesterol on the ketogenic diet, otherwise known as the lean mass hyper-responder phenotype. Dawn specifically asks Dom about an article he and other researchers published in the Journal of Clinical Lipidology on this topic, titled “Elevated LDL-cholesterol levels among lean mass hyper-responders on low-carbohydrate ketogenic diets deserve urgent clinical attention and further research.” [00:45:16] Dawn explains that there is no one-size fits all diet, with some people breezing through a ketogenic diet and others who do not tolerate it as well. She mentions that Dom had a review published a few years ago that examined genetic and other markers in an effort to identify how people might respond to a ketogenic diet, the goal being to identify individuals who were most likely to benefit from a ketogenic diet, and pinpoint individuals who might be at risk of adverse health outcomes because of the diet. Dawn asks Dom to walk through this review and explain its findings. [00:50:03] Ken mentions that Dom has done a lot of research on hyperbaric oxygen, which is a well-established treatment for decompression sickness, which is a risk among divers. Ken goes on to explain that hyperbaric oxygen therapy is now being used to treat several medical conditions including traumatic brain injury. There is controversy, however, regarding this therapy. Ken asks Dom to give a short primer on hyperbaric oxygen and why it has lately attracted so much attention. [00:52:56] Dawn follows up by jumping into a discussion about the NASA project NEEMO that sends crews of astronauts, aquanauts, engineers, and scientists to live in a facility at the bottom of the Atlantic, known as Aquarius. It is the world’s only undersea research station. Dawn explains that NEEMO provides a good analog for space exploration, by mimicking the high physiological stress environment that astronauts experience during space missions. Dawn explains that she was on the crew of NEEMO 21 and Dom was on the crew of NEEMO 22, and Dom’s wife was a NEEMO support diver during NEEMO 22. She later became a part of the all-women crew in NEEMO 23. Dawn asks Dom to talk about his experience on NEEMO as well as the research he conducted. [00:57:58] Dawn asks about Dom’s paper he published after his experience on NEEMO, titled “Human Adaptations to Multiday Saturation on NASA NEEMO,” which explored the physical and psychological effects of living in a multiday hyperbaric environment. Dawn asks Dom to discuss this paper’s findings and its significance. [01:04:25] Ken mentions that Dom and his wife have moved to a farm and asks what life on the farm is like. Links: Dominic D’Agostino USF bio Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio  

Today we have the former chief scientist of NASA’s Human Research Program, Dr. Mark Shelhamer. Mark specializes in neurovestibular adaptation to spaceflight. He is an otolaryngology professor at Johns Hopkins School of Medicine and the director of the school’s Human Spaceflight Lab. He also the director and founder of the Bioastronautics at Hopkins initiative. In addition to his work with NASA, Mark is an advisor to the commercial and consumer spaceflight industry. In today’s interview, we talk to Mark about some of this work, as well as the research he conducted on the first all-civilian crew that successfully orbited the Earth for three days in a SpaceX capsule. We mostly talk to Mark, however, about how the harsh conditions of space imperil humans. We have a fascinating discussion about Mark’s role in NASA’s planned human mission to Mars and how he is investigating ways to maintain the health and performance of astronauts on such a long-duration spaceflight.  We also discuss how the lessons Mark is learning about how the lessons of human spaceflight can be applied to healthcare on Earth. Show notes: [00:02:42] Dawn starts the interview mentioning that Mark grew up in Philadelphia in the ‘70s. She asks Mark what he was like as a kid. [00:03:32] Dawn asks if it is true that Mark played drums in a band in school. [00:03:54] Ken asks Mark to talk about an uncle who was key in fostering Mark’s interest in math and science. [00:05:31] Ken mentions that Mark was only 10 years old when he took up an interest in electronics and asks what sparked that and what electronics he specifically found interesting. [00:08:14] Dawn mentions that Mark attended Drexel University and initially wanted to become an electrical engineer but changed his mind somewhere along the way. Dawn asks what caused this shift. [00:10:20] Ken asks Mark why he selected to attend MIT after Drexel. [00:13:52] Ken asks Mark how he ended up at Johns Hopkins after finishing his studies at MIT. [00:15:52] Dawn mentions that when Mark arrived at Johns Hopkins as a postdoc fellow in 1990, he continued the research he had been doing at MIT on sensory motor physiology and modeling, including astronaut adaptation to space flight. Dawn asks Mark to give an overview of this research as well as how he tracked back into studying astronauts. [00:17:15] Ken mentions Mark’s 2007 book “Nonlinear Dynamics in Physiology: A State-Space Approach,” which provides mathematical-computational tools for analyzing experimental data. Ken asks Mark to talk about the book and its goals. [00:20:43] Ken mentions that Mark has done quite a bit of research into motion sickness and vestibular issues, and asks about his more recent work on Space Motion Sickness. [00:24:53] Dawn explains that on Mark’s Wikipedia page, there’s a reference to his pioneering work on a multidisciplinary approach to human space flight research. She asks Mark to give an overview of this work. [00:29:17] Dawn explains that spaceflight has widespread effects on many different body systems at the same time, and that Mark has been an advocate for developing approaches to examining all these interactions in a rigorous way. Dawn asks if Mark feels that we should be taking this rigorous multidisciplinary approach and applying it to terrestrial medicine as well. [00:34:08] Ken asks Mark to talk about some of the progress he has made in convincing certain groups that they need to embrace a multidisciplinary approach to their research. [00:38:37] Dawn mentions that getting people, especially groups, to change their approach to research can be a daunting task. She goes on to mention that Mark has been quoted as saying “If there’s one thing I’m known for, it’s banging my head against the wall trying to convince people to do integrative research.” Dawn asks Mark how many scars he has on his forehead from these efforts. [00:43:00] Dawn asks Mark to talk about his informal expertise on the history of NASA’s early stages of human spaceflight. [00:48:54] Dawn explains that we may be on the cusp of another exciting time with NASA’s Artemis program and plans to return to the moon. Dawn also mentions that two years ago, the first all-civilian crew was sent on a 3-day mission orbiting Earth by SpaceX in a Falcon rocket. Dawn explains that there were several research projects related to Inspiration4 and that Mark was the principal investigator for one of them. Dawn asks Mark to talk about this project, which is part of a NASA-supported experiment to test and study astronauts through the year 2033. [00:57:16] Ken points out the success of Apollo 17’s scientific inquiries thanks to Jack Schmitt being a scientist who had the chance to fly the mission as an astronaut. Ken and Mark talk about the importance of having more subject-matter experts go into space so that detailed spontaneous scientific observations can be made. [01:00:16] Dawn mentions that in 2013, Mark took leave from Johns Hopkins to serve as the chief scientist of NASA’s Human Research Program. In this capacity, Mark particularly looked at the effects of space radiation on people as well as the behavioral risks of being confined with a small group of people in tight quarters on a long-duration spaceflight. Dawn asks Mark to talk more about this research. [01:04:43] Mark Ken and Dawn discuss the psychological, mechanical, and physiological pros and cons of artificial gravity for a Mars mission. [01:07:39] Dawn mentions that most human research has been focused on keeping people healthy in space. However, one thing that Mark is excited about is the potential of spaceflight research to enhance terrestrial healthcare. Dawn mentions that not everyone sees the broader scientific value of human spaceflight research. To address this, Mark and a group of colleagues published a paper in 2020 titled, “Selected discoveries from human research in space that are relevant to human health on earth.” Dawn asks Mark to talk about what some of the reservations are that people have about the ability of spaceflight research to enhance terrestrial healthcare. [01:12:23] Ken mentions that this 2020 paper looked at five areas of physiology that support Mark’s contention of the broader implications of spaceflight research. Ken asks Mark to discuss these and their potential relevance to scientific and medical issues on Earth. [01:17:53] Ken starts a dialogue about the assessment of risk for a Mars mission, as well as proposing pharmacological interventions for things like bone loss in long duration space flights. [01:21:03] Ken explains that NASA estimates that it will take around seven months to get to Mars with a good planetary alignment. Ken goes on to explain that NASA is planning to send humans to Mars in the 2030s and asks Mark to give his thoughts about a future Mars Mission and the role that human research might play in enabling such missions. [01:26:08] Dawn explains that in addition to Mark’s NASA work, he also has projects involving SpaceX and Blue Origin, and mentions that he must be very busy at the moment. [01:26:45] Dawn mentions that Elon Musk has gone on record as saying that SpaceX will land humans on Mars by 2026 and asks Mark what his take on this is. [01:28:16] Ken asks if it is true that Mark remains an avid ham radio hobbyist and still plays drums in his spare time. [01:29:32] Dawn mentions that Mark’s high school is so proud of what he has accomplished in his career that last year he was inducted into his high school’s inaugural Hall of Fame class. [01:31:15] Dawn asks if Mark’s previously mentioned connection to the Hubble Space telescope research program is in fact his wife. [01:31:48] Dawn mentions that she has heard that Mark is a cat person and to close the interview asks Mark about that.

Back in early days of the COVID-19 pandemic, Dr. John Ioannidis wrote an article in March of 2020 questioning government statistics about the fatality rate associated with COVID-19. The backlash was swift and brutal and John’s reputation as one of the most influential scientists in the world took a beating. Today, John makes his second appearance on STEM-Talk to discuss his extensive research into the COVID-19 pandemic as well as the public shaming he received in 2020 for questioning the World Health Organization’s prediction of a 3.4 percent fatality rate associated with COVID-19. John also talks about his most recent peer-reviewed paper that looked at the age-stratified infection fatality rate of COVID-19 in the non-elderly population.  The study found that the pre-vaccination fatality rate for those infected may have been as low as 0.03 percent for people under 60 years old, and 0.07 percent for people under 70, far below the World Health Organization’s prediction of a 3.4 percent fatality rate. In today’s episode, John walks us through this paper, which was published in January, as well as what he describes as the U.S. government’s bungled response to COVID-19. He also discusses the importance of collecting reliable data in the future to guide disease modelers and governments before they make decisions of monumental significance like lockdowns. He goes on to share how he underestimated the power that politics and the media, or powers outside of science, can have on science. Over the past two decades, John’s research has earned him a global reputation as a consummate physician and researcher, which contributed to The Atlantic describing John in 2010 as one of the most influential scientists alive. He is a professor of Medicine, Epidemiology and Population Health as well as a statistician and professor of biomedical data science at Stanford University. Back in 2018 when we interviewed John on episode 77 of STEM-Talk, we talked to him about his 2005 paper questioning the reliability of most medical research. The paper, titled, “Why Most Published Research Findings Are False,” found that much of the medical science reported in peer-reviewed journals is flawed and cannot be replicated. The paper is the most citied article in the history of the journal PLoS Medicine and has been viewed more than 3 million times. Show notes: [00:03:16] Dawn opens the interview welcoming John back to STEM-Talk. his last appearance being in 2018. Dawn explains that when John last appeared on STEM-Talk in 2018, he was described by Atlantic Magazine as “one of the most influential scientists alive.” But in the intervening years, John became public enemy number one in 2020 after a paper he published questioning government statistics about COVID 19’s fatality rate. Dawn asks John if it’s fair to say that he has been on a rather rocky ride for the past few years. [00:03:54] Dawn explains that John was trained at Harvard and Tufts universities in internal medicine and infectious disease, and asks John what led him to study infectious disease. [00:04:54] Ken asks John about his initial thoughts in 2019 when he first heard the reports coming out of China about COVID-19. [00:05:52] Ken explains that in March of 2020, John fell into some hot water for writing a piece questioning the 3.4 percent fatality rate associated with COVID-19. John found this number to be inflated and wrote that while COVID-19 was indeed a threat, it did not behave like the Spanish Flu or a pandemic that would lead to a 3.4 percent fatality rate. Ken asks John how he came to this conclusion. [00:08:37] The article that John wrote in 2020 was titled “A fiasco in the making? As the coronavirus pandemic takes hold, we are making decisions without reliable data.” John argued in his article that the data collected in the first three months of the pandemic was “utterly unreliable.” He went on to write that no one had a good way of knowing how many people were infected and therefore how the pandemic would evolve over time. Dawn asks John what could have been done so that governments and health agencies could have more accurately estimated incidents of new infections, particularly in the early months of the pandemic. [00:10:19] Dawn mentions that John initially supported the lockdown, but only as a temporary measure, and that he was of the mind that after February of 2020, we had missed the window to nip the pandemic in the bud. Dawn goes on to say that John believed that if we had acted earlier and more aggressively with testing, tracing, and isolating, like in South Korea, that we could have significantly slowed the spread of the virus. Dawn asks if John still feels this way now. [00:12:53] Dawn mentions that John wrote that the bulk of the mortalities related to COVID-19 occurred in people with limited life expectancy rather than young people. Dawn goes on to say that John was criticized for this, accused of minimizing the lives of the elderly and was even referred to as a “heartless granny killer.” Dawn asks John to expand on his point that age predicts mortality better than comorbidities. [00:15:16] Ken follows up regarding the disproportionate infections in nursing homes, mentioning that, among other stories, New York City showed very negative outcomes in terms of nursing-home populations. [00:16:13] Dawn asks if John investigated the nosocomial spread of COVID-19. [00:17:53] Ken mentions that one of the things we heard early on in the pandemic, was talk of flattening the curve so that we wouldn’t overwhelm hospitals. Ken asks John for his thoughts about this. [00:20:04] Dawn asks John what he thought of the Great Barrington Declaration, a paper that questioned school closings, lockdowns, travel restrictions and other governmental responses to the COVID-19 pandemic. Dawn goes on to mention that one of the authors of that paper, Dr. Martin Kulldorff, was our guest on episode 132 of STEM-Talk. Dawn goes on to say that Martin and his co-authors recommended protecting senior citizens and others who were most at risk from COVID, while allowing young people and others who face minimal risk to lead their normal lives. Dawn asks John about the recommendations found in the Great Barrington Declaration. [00:23:26] Ken mentions that outrage propagated by social media and news sources became such a negative force that it shut down civil discourse in public and academic circles. Ken goes on to say that this led to harsh control over conversations regarding important topics. There were swift attacks against anyone who dissented with official narratives, no matter how well founded someone’s opinions were. Ken asks John about his experience now that he has being on the receiving end of these brutal attacks. [00:27:00] Ken follows up and agreees that the self-censorship among scientists with regards to COVID-19 has been severe and problematic. [00:28:33] Dawn brings up John’s recent paper published in January of this year in Environmental Research. Dawn explains that this paper points out that the largest burden of COVID-19 is carried by the elderly, but that 94 percent of the global population is younger than 70 years old, and 86 percent is younger than 60. Dawn goes on to explain that John set out to accurately estimate the infection fatality rate of COVID-19 among non-elderly people in the absence of vaccination or prior infection. Dawn asks John how he and his co-authors came together to work on this study. [00:31:45] Dawn mentions that John’s aforementioned study reported infection survival rates around the world. John found that wealthy nations had infection survival rates of 99.962 percent for those under 60, and 99.902 percent for those under 70. In poorer nations, however, the survival rates were even better: 99.992 percent and 99.988 percent respectively. Dawn goes on to mention that John and his co-authors speculate that lower obesity rates in poorer countries may have improved their survival rates, and asks John how the U.S. would have fared if the obesity rate was at levels more common in the 1970s or ‘80s. [00:35:08] Ken mentions that unsurprisingly the countries hit the hardest by COVID-19, like Italy and China, had two of the most elderly populations in the world. [00:38:09] Dawn mentions that John’s paper noted that 44 percent of the population had already been infected with COVID-19 before Omicron arrived in the fall of 2021. Because of this, John points out in the paper that an infection rate of 50 percent would have only caused modestly higher fatality rates than seasonal flu fatalities for those under 70. Dawn asks John to elaborate on this. [00:40:52] Dawn mentions that around the time John published his paper in STAT in March of 2020, the Imperial College of London predicted Covid-19 would kill 40 million people. [00:41:56] Ken mentions that miscalculations like the one by the Imperial College of London were unfortunate because they prompted lockdowns and other heavy-handed responses from governments. Ken goes on to say that John wrote in 2020 that we need data to inform us about the rationale of lockdowns, mask mandates and social distancing measures. At a minimum, Ken said, we needed unbiased prevalence and incidence data for the evolving infectious load to guide decision-making. Ken asks John for his thoughts about why this never happened. [00:46:34] Ken asks John what were some of the unintended consequences that resulted from lockdowns, school closures, and travel bans. [00:49:47] Dawn mentions that John has published dozens of peer-reviewed COVID-19 related papers. John has mentioned before that any scientific papers will have some weaknesses. Dawn asks John what, in hindsight, he sees as weaknesses in his papers. [00:50:41] Ken asks about John’s investigation into the recent study commissioned by the British nonprofit Cochrane that found no clear reduction in respiratory viral infection as a result of mask mandates. Ken mentions that the paper noted that the use of medical/surgical masks, including N-95 masks, were not effective in reducing the spread of acute respiratory viruses. [00:55:02] Ken mentions a Zoom call he was on with a government official who was alone in his house wearing a mask during the Zoom call. Ken discusses the gentleman’s response after he was asked about wearing the mask even though he at home by himself. [00:56:48] With respect to randomized controlled trials regarding the effectiveness of masks, Ken mentions that the media’s portrayal of such studies shows that the media does not understand statistics, and specifically the difference between relative and absolute risk. [00:57:51] Ken launches into a discussion about the education of journalists in modern times, and how education in journalism should include a sophisticated understanding of statistics. [01:00:24] Ken asks John what his thoughts are about the possibility of future pandemics and how this kind of situation might be handled differently. [01:02:50] Ken mentions the issues created by funding agencies during times of pandemic and other world shaping events. [01:03:41] Ken explains that trust, or lack thereof, in institutions and the media has turned out to be a key factor in people’s reaction to non-pharmaceutical interventions such as lockdowns and mask mandates and vaccine mandates. Ken goes on to say that surveys of trust are showing a substantial decline and offers that there may be strong negative consequences from this lack of trust in the future. Ken goes on to say that this trust could, of course, be reestablished through transparency and accountability and asks John if he sees this happening anytime soon. [01:06:28] Ken closes the interview asking John if there are any other COVID-19 studies he is working on or hopes to pursue. Links: John Ioannidis bio Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio