Episode 178: Karl Herrup discusses the shortcomings of Alzheimer’s research

Today we have JP Errico, a scientist and inventor whose work focuses on neuroimmunology and the many ways it impacts cellular metabolism, inflammation, mental health and how we age. He recently joined IHMC as a Senior Research Scientist. JP is particularly known for his research on vagus-nerve stimulation and is the author of the book, The Vagus-Immune Connection: Harness Your Vagus Nerve to Manage Stress, Prevent Immune Dysregulation, and Avoid Chronic Disease. He also is the co-host of the podcast, The Health Upgrade. JP has more than 250 patents and is the founder of ElectroCore, a company that specializes in neuromodulation and noninvasive vagus-nerve stimulation. He has an undergraduate degree in aeronautical engineering from the Massachusetts Institute of Technology and worked at Lincoln Laboratories. JP also holds graduate degrees in both law and mechanical/materials engineering from Duke University. Show notes: [00:03:08] Tim opens our interview mentioning that as a child JP was focused on both sports and academics. [00:04:50] Tim talks about how hard it is to find quality math and science education today similar to what JP experienced at his high school. [00:05:16] Tim asks JP what it was that led him to pursue an undergraduate degree at MIT. [00:05:53] Tim asks if it was always JP’s plan to go into aeronautical engineering. [00:07:22] Tim mentions that as a kid, JP would scour bookstores and libraries for textbooks on physics and quantum mechanics and asks JP if there were any books that particularly inspired him. [00:10:12] Ken mentions that after MIT, JP went to Duke University where he pursued mechanical engineering and also went to law school. Given this workload, Ken asks if JP ever had any free time while studying at Duke. [00:13:26] Tim mentions that while JP was in law school, he got a job at a patent firm. After obtaining his law degree, JP’s uncle called and offered JP an opportunity. [00:17:42] Tim explains that JP’s career has focused on neuroimmunology, or the study of how the nervous system and immune system interact. Neuroimmunology affects a wide range of health factors including inflammation, mental health and aging. Tim also explains that JP has recently authored a book on neuroimmunology titled “The Vagus Immune Connection: Harness Your Vagus Nerve to Manage Stress, Prevent Immune Dysregulation and Avoid Chronic Disease.” Tim asks JP to touch on the key features of neuroimmunology that people should be aware of. [00:21:59] Tim asks JP to touch on the epigenetic factors regarding neuroimmunology. [00:25:01] Since JP brought up Dr. Kevin Tracey’s work, Ken mentions that Kevin was recently interviewed on STEM-Talk episode 172 and encourages listeners to listen to that episode for more context on the vagus nerve and neuroimmunology. [00:25:48] JP talks about how he stumbled upon the idea of how stimulating a nerve may have the same clinical benefit that sometimes occurs as a result of cutting a nerve. [00:28:16] Tim talks about the unintended consequences he observed as surgeon when he cut a patient’s vagus nerve. [00:30:50] Ken mentions that another area where JP has had impact with respect to stimulating the vagus nerve is the treatment of asthma and asks JP to talk about his findings in this area. [00:40:10] Tim notes that after JP knew that non-invasive approaches to vagus-nerve stimulation were possible, he went on to optimize a delivery device. These efforts resulted in a device called gamaCore. Tim asks JP to talk about this device and how it works. [00:43:27] Tim asks JP to talk about what it feels like for patients to have their vagus nerve stimulated. [00:44:50] Ken asks if JP thinks that his and others’ work in vagus-nerve stimulation inspired the development of similar devices for orthopedic pain, where the device is implanted near the nerve on the knee or other area experiencing pain.

Today we have Dr. Karl Herrup, a neurobiologist known for his investigations into the roles that DNA damage and noncoding genetic variants have in Alzheimer’s disease. Joining Ken today to interview Karl is Dr. Tommy Wood, a visiting scientist here at IHMC.  Tommy also is an associate professor of pediatrics and neuroscience at the University of Washington, where he focuses on brain health across lifespan. He has been our guest several times on STEM-Talk and we will have links to those interviews in our show notes for today’s episode. After more than a century of research, the underlying cause of Alzheimer’s remains a mystery. For the past few decades, the leading theory has been the amyloid cascade hypothesis, which proposes that abnormal amyloid plaques in the brain are the central cause of the disease. Today we talk to Karl about his lab and research as well as his view that the amyloid cascade hypothesis is not only flawed,  but also could be holding back research for a cure of Alzheimer’s. A professor of neurobiology and an investigator in the Alzheimer’s Disease Research Center at the University of Pittsburgh School of Medicine, Herrup is the author of How Not to Study a Disease: The Story of Alzheimer’s. Show notes: [00:03:50] Tommy asks Karl what he was like as a kid to open the interview. [00:04:36] Tommy asks Karl about his educational environment growing up. [00:05:10] Ken mentions that Karl went to Brandies University originally with the intent of becoming a physician and asks Karl what happened to change his mind. [00:06:14] Ken asks Karl if it is true that his father was disappointed with Karl’s decision to abandon medical school in favor of genetics. [00:07:02] Tommy mentions that Karl began researching genetics in the late 1960s when researchers were just beginning to unravel the secrets of DNA. Tommy asks Karl to discuss why this was such an exciting time to study genetics. [00:08:38] Tommy asks Karl what prompted him to pursue a PhD in neuroscience. [00:11:34] Continuing on the theme of happy accidents, Ken asks if it was also an accident that led to Karl moving to Switzerland for a second post-doc. [00:12:36] Ken asks Karl to expound on his experience taking an overseas post-doc, which was not a common practice in the 1970s. [00:14:11] Ken mentions that Karl has seemed to benefit in his life from the combination of preparation and the willingness to explore opportunities that present themselves. [00:15:00] Tommy mentions that when Karl arrived back in the US from Switzerland, he accepted a faculty position at Yale and asks him to discuss this experience. [00:17:06] Tommy mentions that after Yale, Karl had several faculty appointments, including a seven-year stint in Hong Kong, and asks Karl to talk about that experience. [00:21:36] Tommy asks Karl why, in 2019, he moved back to his hometown to become a professor of neurobiology at the University of Pittsburgh and co-investigator at the university’s Alzheimer’s research center. [00:24:45] Ken asks Karl to talk about his lab at the University of Pittsburgh, which focuses on the biology of neurodegeneration. [00:26:32] Ken asks Karl if there was anything specific that caused him to shift his focus at this stage in his career so heavily towards Alzheimer’s research. [00:28:21] Tommy comments on Karl’s hypothesis of the aging brain, noting that it would make sense for the same processes involved in the developing brain to relate to what we see in the aging brain, as these processes are continuous throughout the lifespan. [00:29:54] Tommy pivots to talk about Karl’s book, entitled “How Not to Study a Disease: The Story of Alzheimer’s” for which Karl interviewed a number of experts and colleagues, asking each one to define Alzheimer’s disease in their own words. [00:30:51] Tommy reiterates the point that we still do not have a universally accepted definition of Alzheimer’s disease and asks Karl wh...

Today we have Dr. Frank Butler, a retired Navy Undersea Medical Officer and an ophthalmologist who served as a Navy SEAL platoon commander prior to attending medical school. Just a few weeks after our interview, President Joe Biden awarded Frank a Presidential Citizens Medal during a White House ceremony. The medal is one of the highest honors a civilian can receive and recognized Frank’s many contributions to civilian and military trauma care. Frank is credited with founding Tactical Combat Causality Care, also known as TC Three, which has transformed battlefield medical care and saved thousands of lives.  TCCC is now used throughout the U.S. military and much of the world. In today’s interview, we talk to Frank about his recent book, “Tell Them Yourself: It’s Not Your Day to Die,” which describes the challenges and improvements TCCC has experienced over the past three decades. Frank spent most of his 26-year career in Navy Medicine supporting the Special Operations community. He served a five-year stint as a Diving Medical Research officer at the Navy Experimental Diving Unit in Panama City, Fla., where he helped develop many of the diving techniques and procedures used by Navy SEALs today. Show notes: [00:03:31] Dawn opens the interview asking Frank what it was like growing up in Savannah, Ga., in the 50s and 60s. [00:04:40] Dawn asks Frank about his father, who was an industrial engineer, and who became director of urban housing in Savannah during a time when the city was developing public housing. [00:05:47] Ken asks Frank if it’s true that most of his family went into the medical field. [00:06:33] Ken asks Frank about his experience attending a Navy SEALs demonstration during his sophomore year of college. [00:08:09] Dawn asks Frank about his experience going through Navy SEAL training, particularly the Basic Underwater Demolition SEALs School. [00:09:29] Dawn asks if it’s true that five people in Frank’s family have become Navy SEALs. [00:10:08] Ken explains that after Frank left the SEALs in 1975, he had to figure out what to do next with his life. Frank talks about what led to his decision to go to medical school. [00:11:14] Ken asks Frank how he ended up at Jacksonville Naval Hospital to do an internship in family medicine. [00:11:46] Dawn explains that after Frank’s internship, he was assigned to the Navy Experimental Dive Unit. She asks him to talk about this experience. [00:12:25] Frank talks about some of the projects he worked on during this period. [00:14:43] Ken asks Frank how he decided on ophthalmology as his surgical specialization. [00:15:47] Dawn asks Frank what his experience as a resident at Bethesda Naval Hospital was like. [00:16:52] Dawn explains that after Frank completed his residency, he was assigned to Pensacola Naval Hospital. Dawn asks Frank how he ended up becoming the biomedical research director for the Navy SEALs. [00:18:48] Ken mentions that Frank worked on several important projects as research director for the SEALs, including battlefield trauma care, a tactical athlete program, improved treatment of decompression sickness, and the Navy SEAL nutrition guide. Ken begins by asking Frank to talk about his work on the tactical athlete program. [00:20:33] Dawn explains that another one of Frank’s projects as research director for the SEALs was the design of the Navy special warfare decompression computer. Dawn asks Frank to explain what a decompression computer does for a diver. [00:21:35] Dawn asks Frank to elaborate on the process of designing this decompression computer and the algorithm as well as the process of getting it approved for the Navy. [00:23:31] Ken asks Frank to talk about a program he worked on to promote refractive surgery. While this program was initially designed to improve combat vision for SEALs, the program has expanded to all active-duty service members, including aviators.

Today our guest is Dr. JoAnn Manson, an endocrinologist, epidemiologist, and Principal Investigator of several research studies, including the landmark Women’s Health Initiative. She is a highly cited researcher and was one of the physicians featured in the National Library of Medicine’s exhibition, History of American Women Physicians. Her primary research interests include clinical prevention trials of nutritional and lifestyle factors related to heart disease, diabetes, and cancer and the role of endogenous and exogenous estrogens as determinants of chronic disease. Show notes: [00:02:53] Dawn kicks off the interview by asking JoAnn what it was that drew her to endocrinology. [00:04:33] Ken asks how the things JoAnn witnessed in her early medical practice influenced her interest in disease prevention. [00:05:51] Dawn asks JoAnn to discuss how her mother, who suffered from ovarian cancer, influenced JoAnn’s focus on women’s health. [00:06:40] Dawn asks JoAnn what prompted her interest in clinical research. [00:08:06] Noting the difference between public health and laboratory medical research, Dawn asks JoAnn what the most valuable thing is that she learned from her master’s and Ph.D. work in public health at Harvard. [00:09:10] Ken mentions that while JoAnn and many others are interested in the prevention of disease, our healthcare system does not seem focused on prevention. Ken goes on to asks if this was part of what led JoAnn to work on the Nurses’ Health Study. [00:10:17] Ken asks JoAnn to give an overview of the Nurses’ Health Study for listeners who may not be familiar. [00:11:41] Dawn explains that the Nurses’ Health Study found that women taking hormone therapy had a lower risk of heart disease and a reduction in all-cause mortality. Dawn asks JoAnn to talk about this finding. [00:15:00] Ken asks JoAnn what the impact of the Nurses’ Study has been on public health and women’s health in general. [00:16:29] Dawn asks JoAnn about her experience being a principal investigator in the Women’s Health Initiative starting in 1993. [00:18:17] Ken asks JoAnn to give context regarding how the Women’s Health Initiative (WHI) was designed, how the women were recruited, and what the specific questions were that the study aimed to answer. [00:21:34] Dawn mentions that the three interventions that were evaluated in the WHI were hormone therapy; calcium and vitamin D supplementation; and a low-fat diet. Dawn starts by asking JoAnn about the hormone therapy interventions, and how it was decided which hormone therapies to test. [00:24:25] Dawn asks JoAnn to give some context to the finding from the WHI that women taking the combination of conjugated estrogen and medroxyprogesterone acetate had higher risks of breast cancer and stroke. [00:27:01] Ken asks if the worse outcomes from hormone therapy for older women was due to their advanced age, or the hormone therapy itself. [00:30:25] Ken asks JoAnn to talk about the risk factors for breast cancer that were uncovered by the WHI. [00:35:38] Dawn explains that because of the WHI’s findings, it is more common to use transdermal estradiol, as opposed to the oral form evaluated in the original trial. Dawn asks JoAnn to explain how the different ways these hormone formulations are processed in the body affects the risk benefit ratio. [00:39:04] Dawn asks if these transdermal estradiol treatments might have benefits regarding cognitive decline. [00:43:26] Ken asks JoAnn for her thoughts on the overuse and potential misuse of the term ‘bioidentical hormones.’ Ken goes on to note that the term has seemingly become more related to marketing and further distanced from clinical science. [00:46:48] Dawn asks JoAnn to talk about the role that perimenopausal birth control decisions can play in the management of hot flashes for women in their 40s and 50s. [00:49:14] Ken shifts the conversation to discuss the second pillar of the WHI,

Today we have Dr. Hans Van Dongen, director of the Sleep and Performance Research Center at Washington State University in Spokane. Dr. Kevin Gluck, a senior research scientist at IHMC, joins Dr. Ken Ford to interview Hans about his studies on inter-individual differences in vulnerability to fatigue as well as the cumulative cognitive deficits that follow chronic sleep restriction. Hans is known for his mathematical modeling of fatigue’s effects on performance. At the Sleep and Performance Research Center, Hans and his colleagues investigate how sleep loss and circadian misalignment impact brain function, cognition and behavior. Show notes: [00:02:50] Kevin opens the interview by asking Hans about his childhood growing up in The Netherlands. [00:03:23] Ken asks Hans what he was like as a kid. [00:03:50] Kevin mentions Hans’s father was a math and science teacher and wonders if that influenced Hans’ interest in science. [00:04:48] Hans talks about attending Leiden University and explains why he majored in astrophysics. [00:06:09] Hans shares how working in a psychophysiology lab put him on a path to specialize in sleep research. [00:08:00] Hans talks about how he was part of a study that proved the morning-evening chronotype was a biological trait, rather than a psychological one. [00:09:55] Ken asks Hans what led him to take a post-doc position at the University of Pennsylvania. [00:11:22] Hans explains what led him to move from the University of Pennsylvania to Washington State University. [00:13:36] Ken mentions that The Sleep and Performance Research Center, where Hans serves as the director, is a coalition of basic and applied research laboratories that aim to understand the neurobiology of sleep and sleep loss. Ken goes on to mention that Hans and his colleagues investigate sleep and biological rhythms, and their impact on health and performance. Kevin asks Hans to give an overview of what sleep loss is and the effect it has on our metabolism, immune system, and cognitive performance. [00:15:57] Kevin mentions Hans’ recent paper which investigated how circadian misalignment due to night shift work has been associated with an elevated risk of chronic disease. The paper demonstrated that just a few days of being on a night shift schedule throws off protein rhythms related to blood glucose regulation, energy metabolism, and inflammation. Kevin asks Hans to talk more about the findings. [00:21:18] Ken asks how long it takes for a person’s circadian rhythm to normalize after ceasing to work night shifts. [00:22:13] Kevin brings up Hans’ paper on the continually operating neurobiological mechanisms of homeostatic and circadian processes and their effects on neurobehavioral performance. Before asking about the paper itself, Kevin asks Hans to give an overview of the homeostatic process and its relationship to the circadian process. [00:24:14] Ken notes that the bio-behavioral function and evolutionary advantage of the circadian process is widely recognized, but that the neurobiology of the homeostatic process and its effects on performance are still poorly understood. In a 2011 paper, Hans attempted to shed light on the underlying mechanisms of the homeostatic process to provide an explanation for why the buildup of homeostatic pressure resulting from sleep loss leads to instability in vigilant attention. To explore this, Hans first explored the time-on-task effect. Ken asks Hans to explain the time-on-task effect and its role in cognitive performance. [00:27:06] Kevin brings up the “local sleep hypothesis,” which attempts to explain the time-on-task effect. According to the local sleep hypothesis, groups of neurons involved in performing a task will “fall asleep” as a homeostatic consequence of sustained use, which leads to an interruption in information processing, leading to impaired performance. Kevin asks Hans what empirical and scientific evidence exists for the hypothesis...

Today we have Dr. Rudolph E. Tanzi, who is perhaps best known for co-discovering all three familial early-onset Alzheimer's disease genes. In addition, Rudy’s lab was the first to use human stem cells to create three-dimensional human brain organoids and three-dimensional neural-glial culture models of Alzheimer’s disease, which became known as “Alzheimer’s-in-a-Dish.” These models were the first to recapitulate all three of the key pathological hallmarks of Alzheimer’s disease and have made drug screenings faster and cheaper. Rudy is the director of the Genetics and Aging Research Unit as well as the director of the Henry and Allison McCance Center for Brain Health. Rudy is also co-Director of the Massachusetts General Institute for Neurodegenerative Disease at Massachusetts General Hospital and serves as the Joseph P. and Rose F. Kennedy Professor of Neurology at Harvard Medical School. Rudy has published more than 700 research papers and is one of the top 50 most cited neuroscientists in the world. He is author of “Decoding Darkness,” and a co-author of two books with Deepak Chopra, “Super Brain” and “The Healing Self.” Show notes: [00:03:18] Ken opens the interview mentioning that Rudy began playing the accordion when he was just seven years old. Ken goes on to ask Rudy about the time his father gave him a Jimmy Smith album and some advice. [00:05:51] Ken mentions that, in addition to Rudy’s musical talents, he was also interested in science growing up. Ken asks about Rudy’s participation in the Westinghouse Science Talent Search and what that experience was like. [00:07:09] Ken asks Rudy about growing up in Cranston, Road Island. [00:08:39] Rudy talks about how he ended up at the University of Rochester after high school. [00:09:51] Ken mentions that both Rudy’s grandfather and father passed away at the age of 45. Ken asks Rudy if this played a role in his pursuit of a career in genetics research. [00:10:57] Rudy explains how he chose Harvard Medical School for his Ph.D. [00:12:47] Ken pivots to ask Rudy about his time working with Jim Gusella in the early 80’s at Mass General, where they were the first to ever find a disease gene. Family studies at the time had shown that the Huntington's disease gene was linked to a polymorphic DNA marker. Rudy talks about this discovery and how the chromosomal localization of the Huntington's disease gene was the first step in using recombinant DNA technology to identify the primary genetic defect in this disorder. [00:16:07] Ken asks Rudy about his work in 1987, when he discovered the first Alzheimer’s gene, recombinant DNA technology, which causes the production of amyloid. Ken goes on to explain that mutations in the APP gene can cause a rare form of early onset Alzheimer’s. Rudy talks about the paper that came out in “Science” that detailed this discovery. [00:18:38] Rudy discusses his personal philosophy and approach to research. [00:19:43] Ken mentions that in Rudy’s book, Decoding Darkness, he writes that few nightmares on Earth can compare to Alzheimer’s disease. Ken asks Rudy to talk more about this book. [00:21:50] Ken explains that in the same way our physical capabilities will suffer some form of decline with age, it is also expected that we have some decline in memory and cognitive ability as we age as well. However, Ken goes on to say that when people begin to experience age-related memory lapses, it can lead to a lot of anxiety about their genetic predisposition to Alzheimer’s. Ken asks Rudy to talk about the lifestyle factors that play into whether someone predisposed to develop Alzheimer’s can stave off or avoid disease development. [00:26:09] Ken explains that aging appears to intensify when people stop challenging themselves with new things. Given this, Ken asks Rudy what his thoughts are on challenging our brains as they age to protect our cognitive abilities. [00:29:08] Ken asks Rudy about the principal advances in...

Our guest today is Dr. Anurag Singh, the chief medical officer at Timeline Nutrition, a Swiss life-science company that focuses on ways to improve mitochondrial and cellular health. Anurag is particularly known for his research into the gut metabolite, urolithin-A, which has been shown to improve muscle strength, protect immune systems and optimize mitochondrial efficiency. Anurag is an MD in internal medicine with a Ph.D. in immunology. He has led more than 50 randomized clinical trials, many of them focusing on urolithin-A over the past decade. In today’s episode we talk to Anurag about his investigations into urolithin-A and the role it plays as a postbiotic that enhances mitochondrial function. Foods that contain the polyphenols needed to produce urolithin-A include pomegranates, strawberries, raspberries and walnuts. Show notes: [00:02:48] Marcas starts the interview by mentioning that Anurag grew up in India, in Lucknow, and asks what Anurag’s childhood was like. [00:03:56] Marcas follows up, asking Anurag what he was like as a kid, given the competitive environment he grew up in. [00:04:47] Ken asks Anurag if it is true that, at an early age, his parents noticed he was gifted in biology and encouraged him to think about pursuing medical school. [00:05:47] Ken asks if Anurag started medical school at only 18 years of age. [00:06:28] Marcas explains that Anurag went to India’s Armed Forces Medical College for training in internal medicine and asks if it is true that this is one of India’s top medical schools. [00:07:07] Marcas explains that it is typical for graduates from the India Armed Forces Medical College to serve a few years in the Indian army after graduation. Marcas asks Anurag to tell the story of how he was able to go to the U.S. post-graduation rather than serving time in the army. [00:08:00] Ken asks if Anurag’s interest in medical research led him to pursue a Ph.D. in immunology. [00:08:56] Ken asks Anurag what his Ph.D. research was on. [00:09:37] Marcas mentions that in 2009, Anurag accepted a position at Nestlé at a time when the company was entering into the space between food and pharma. Marcas asks Anurag how this move came about. [00:11:20] Ken explains that Anurag quickly became medical director at Nestlé and started initiating clinical trials around food and allergies, as well as research on aging and how the immune system declines with age. Ken asks Anurag to explain what his time at Nestle was like. [00:12:53] Marcas mentions how the shift from practicing physician to research scientist is an interesting course and asks Anurag to talk about a mentor who gave him the advice that led to his career shift. [00:13:55] Ken mentions that in 2014 Anurag joined a Swiss company, Amazentis, as chief medical officer, and later became the lead for their medical and clinical research strategies. Ken asks Anurag to talk about the company and the work he does. [00:15:00] Ken asks Anurag to describe the relationship between Amazentis and Timeline. [00:15:42] Marcas asks Anurag to elaborate on his biotech approach to nutrition science, and how hard biology is used in his nutritional approaches at Amazentis. [00:18:02] Marcas asks Anurag to give listeners an overview of the function and importance of mitochondria. [00:19:15] Ken asks Anurag if there are any other benefits to good mitochondrial health, other than an increased energy supply. [00:20:24] Ken asks Anurag to define the terms “mitochondrial biogenesis” and “mitophagy.” [00:22:13] Marcas pivots to discuss age-related frailty and healthspan, specifically bringing up a study Anurag conducted on a Dutch population comparing active seniors to sedentary seniors. [00:25:09] Ken mentions that Marcas likes to refer to exercise as medicine, given its potent effects on a wide variety of biomarkers. Ken asks Anurag to discuss the importance of exercise. [00:26:59] Following up on the Dutch study,

Few people know as much about inflammation and neuroscience as Dr. Kevin Tracey does. In this episode of STEM-Talk, we learn much from Tracey, who was the first to identify the inflammatory reflex, a physiological mechanism that regulates the body’s immune response to injury and invasion. He is a neurosurgeon, a pioneer in bioelectrical medicine and president and CEO of the Feinstein Institutes for Medical Research in Manhasset, N.Y. The conversation in this episode covers a career spent working on “producing tomorrow’s cures today” in the treatment of inflammatory diseases, including: How the death of his mother from a brain tumor when Tracey was 5 years old ultimately influenced his scientific journey. How the death of a young patient of his from sepsis further fueled his path, leading him to the insight that “good science begins with hard questions,” as Tracey shared in a TedTalk.  The molecular mechanisms of inflammation and the use of vagus nerve stimulation to treat it. His 1987 discovery of tumor necrosis factor (TNF), which contributed to a new class of drugs for inflammatory and autoimmune diseases. Another discovery that allowed him and his colleagues to merge neuroscience and immunology. His work on “The Inflammatory Reflex”, which emphasized the basic neural pathway that reflexively monitors and adjusts the inflammatory response. A sketch he drew while having lunch, which laid out how treating inflammatory diseases using a bioelectronic device might be possible. What advances in bioelectronic medicine he envisions in the next decade, and much more. [00:03:04] Dawn asks Kevin to tell the story of how he developed an interest in science that evolved into him becoming a neurosurgeon. [00:04:56] Dawn mentions that Kevin was a curious youth and asks if it is true that after getting his first car, Kevin removed the entire engine because he wanted to better understand how to do a valve job. [00:06:33] Ken mentions that after Kevin graduated from high school, he enrolled in Boston College where he earned a bachelor’s degree in chemistry. Ken explains that Kevin went to Boston University Medical School for his M.D. and asks Kevin about the transition. [00:08:41] Ken asks if it is true that during Kevin’s first year at medical school his classmates had better luck finding him on the golf course than in the classroom. [00:10:42] Dawn asks Kevin about his transition from medical school to the neurological surgery training program at New York Hospital, home of the Cornell University Medical College. [00:13:11] Dawn pivots to talk about sepsis, which kills more than 350,000 people annually. She asks Kevin to discuss his tragic story of treating a patient with sepsis as a young neurosurgeon and how that changed the trajectory of his career. [00:16:38] Ken explains that since the aforementioned incident, Kevin has focused on determining why septic shock occurs. Ken refers to a Ted Talk of Kevin’s in which he says, “good science begins with hard questions.” Ken asks Kevin to elaborate on this point. [00:20:49] Dawn mentions that Kevin often describes himself as a brain surgeon who is fascinated by inflammation. Dawn asks Kevin how he responds when people ask him what inflammation is. [00:22:29] Ken follows up by explaining that in 1987 Kevin made progress investigating inflammation with his discovery of tumor necrosis factor (TNF), which contributed to a new class of drugs for inflammatory and autoimmune diseases. Ken asks Kevin to discuss this discovery. [00:25:56] Dawn mentions that in the late ‘90s, Kevin made another discovery that allowed him and his colleagues to merge neuroscience and immunology. Before getting into that discovery, Dawn asks Kevin to explain how humans have simple reflex circuits that harmonize the activity of our organs. She also asks him to talk about Charles Sherrington’s Nobel Prize-winning research, which laid the groundwork for contemporary neuroscience by...

In today’s Ask Me Anything episode, Ken and Dawn answer a wide range of questions that cover: A recent FDA approval of a neural implant device for people with degenerative neuromuscular disease or spinal-cord injuries. Global security in the age of AI. A study that looked at ways to optimize glymphatic clearance for people with acute or chronic sleep deprivation. Why more gyms don’t offer blood-flow restriction classes for their clients. Developments in the realm of Generative AI. The tradeoffs between a low-carb diet versus a ketogenic diet. A study on Alzheimer’s titled, “APOE 4 Homozygosity Represents a Distinct Genetic Form of Alzheimer’s Disease.” Plus, Ken reveals his favorite science-fiction author. [00:02:38] Dawn opens the episode with a question for Ken about the FDA’s recent approval of a neural implant device which is touted as a means of allowing people with degenerative neuromuscular disease, or spinal-cord injuries, to interface with external technology via neural signals. The listener asks Ken for his insights into what is being called “brain-computer interface technologies.” [00:05:44] A listener asks Ken if he has a favorite science-fiction writer, or if there is a particular sci-fi series/story that really moves him. [00:08:48] Multiple listeners ask Ken about a paper recently published titled: “APOE 4 Homozygosity Represents a Distinct Genetic Form of Alzheimer’s Disease.” Listeners ask if it is true that people with two copies of APOE4 allele are certain to develop the disease. [00:19:30] A listener asks Ken about his time on the National Security Commission on Artificial Intelligence. The commission issued its report five years ago with specific recommendations on how the government should prepare for and defend against the national security implications of AI. Ken shares his thoughts on the implementation of the commission’s recommendations. [00:21:16] A listener asks Dawn about her collaboration with Dr. Jeff Iliff that looked at a potential approach to optimizing glymphatic clearance for people with acute or chronic sleep deprivation. [00:27:10] A listener asks Ken why more gyms and physical therapy centers don’t have blood flow restriction devices (BFR) available for their clientele, given that studies have shown that BFR improves strength and muscle mass in both young and older adults. (Two STEM-Talk episodes that cover blood-flow restriction include episode 34 and episode 161. [00:28:38] A listener asks Ken for his thoughts on AI given the recent developments in the field, particularly in the realm of Generative AI, with programs like Chat GPT becoming a household name. The listener mentions that one of their friends thinks that AI is about to peak, and another says that AI is just getting warmed up. [00:37:00] A listener writes that they are astounded at how many disorders can be treated with a ketogenic diet and mentions that they themselves have difficulty with a ketogenic diet. Instead, the listener eats low-carb diet and asks if the benefits of a low-carb, non-ketogenic diet are similar to a ketogenic one. [00:38:19] A listener asks if Ken could talk about carotid scans and if this is a test that those with high LDL should consider getting. [00:40:17] A 72-year-old listener explains how they structure their daily exercise routine between resistance and endurance training. The listener asks Ken whether they should focus more on resistance training as they are beginning to lose strength, and if so, how they should implement that given their age and the increasing risk for injury. [00:45:51] To wrap up this episode, a listener asks Ken if he has any new annoyance that he would like to share, as he did in 2022, when he noted his disdain for the phrase “new normal” and the prevalence of cellphone addiction. Links: Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio

Today Dr. David LeMay steps in to co-host with Dr. Ken Ford for our interview with Dr. Charles Serhan. Charles is a Harvard professor best known for his discovery of specialized pro-resolving mediators. SPMs are molecules that can activate the natural resolution of inflammation and help people avoid anti-inflammatory drugs. The discovery of SPMs spurred a paradigm shift in our understanding of inflammation and human disease. Charles is the Simon Gelman Professor of Anesthesia at Harvard Medical School and the director of the Center for Experimental Therapeutics and Reperfusion Injury at Brigham and Women’s Hospital. He also is a co-director of the Brigham Research Institute. David, who was our guest on Episode 69 of STEM-Talk, is a sports medicine and rehabilitation physician with a Pensacola, Florida practice that focuses on lifestyle and performance medicine. He also is a visiting research scientist here at IHMC. Show notes [00:03:33] David opens the interview mentioning that Charles grew up in New York City with a passion for music. David explains that Charles learned to play the vibraphone in junior high and played professionally for a year before going to college. David asks Charles why he decided to pursue science instead of music. [00:04:22] Ken asks Charles what kind of vibraphone he plays. [00:06:02] Ken asks, aside from the desire to help people, if there was something particular about studying science that Charles really enjoyed. [00:06:45] David asks about Charles’ experience at the State University of New York at Stonybrook studying biochemistry and immunohistochemistry. [00:07:16] David asks if there was any carry over of skills for Charles from his career in music to his career in science. [00:08:16] Ken mentions that after Charles earned his bachelor's degree, one of his professors persuaded him to go to New York University for a master's and Ph.D. Ken also mentions that at the time Charles worked in the lab of Gerald Wiseman at Woods Hole Marine Biological Laboratory and asks about that experience. [00:12:37] David asks if this experience led Charles to a focus on neutrophil membrane remodeling for his Ph.D. [00:13:59] David asks Charles if it was at the Karolinska Institute where he met his future wife. [00:14:38] Ken asks Charles about one of his mentors, Michael Heidelberg, who gave Charles advice about how to be a good scientist. [00:17:13] David explains that in the 1990's Charles discovered Specialized Pro-Resolution Mediators and has since pioneered a new field on the utility of SPMs for a variety of inflammatory diseases. [00:25:01] Ken backs up to ask Charles what drew him to study inflammation in the first place and how that led him to do more research on the subject than any other scientist. [00:26:26] David asks Charles to touch on some different types of inflammation that the body experiences. [00:35:12] Ken asks Charles about how a trip to Asia during which he developed a hole in his intestines, resulted in first-hand experience on the importance of controlling inflammation. [00:41:00] David asks if Charles was taking any non-steroidal anti-inflammatory medications when he developed peritonitis. [00:41:53] David asks Charles to explain what non-steroidal anti-inflammatory medications do to the healing process. [00:45:35] David brings up a recent discovery in animal models that as animals age, their ability to produce resolution mediators declines, possibly contributing to the loss of muscle mass with age. [00:48:09] Ken asks Charles to talk about the explosion of research into the potential therapeutic applications of SPMs in the treatment of a variety of chronic diseases known to be driven in part by chronic inflammation. [00:51:06] David asks Charles to explain the differences between resolvins, protectins, and maresins, as well as what role each plays in the healing process. [00:56:04] Ken mentions a review article that Charl...