Dr. Satchin Panda is a professor and researcher at the Salk Institute who has become recognized as one of the world’s leading experts on circadian rhythm. In today’s wide-ranging interview, he discusses how the body’s natural day-night cycle can help us improve our health, get a better night’s sleep and lose weight. He also shares how adopting a lifestyle that is aligned with the body’s natural internal clock can even help us prevent and reverse disease. Satchin also has been generating significant attention for his research into the health benefits of time-restricted eating. He is the author of “The Circadian Code” and in today’s interview he shares how listeners can become involved in a research project he and his colleagues are conducting through a smartphone app called My Circadian Clock. In addition to his work at the Salk Institute, Satchin is also a founding executive member of the Center for Circadian Biology at the University of California, San Diego.  Key topics covered in today’s interview include: [00:03:46] How a rapidly evolving modern society disrupts the interconnectedness of our biological rhythms. [00:13:41] How Satchin became interested in circadian rhythms and metabolism. [00:17:11] Satchin’s first mouse study on time-restricting feeding, which so surprised him that he ended up repeating the study three times. [00:21:37] The role of ketosis in time-restricted eating, particularly in regard to weight loss and potential health benefits. [00:25:01] Whether having black coffee signals the beginning of a person’s eating window. [00:27:31] The potential use of caffeine to treat jet lag induced by international time-zone travel. [00:29:31] Satchin’s mouse studies that looked at obesity and type-2 diabetes. [00:30:58] The dangers of shift work and the importance of sleep. [00:45:39] Satchin talks about the importance of darkness when it comes to sleep and our circadian rhythms. [00:48:42] Satchin’s 2017 paper in Aging Research Reviews titled “ Circadian rhythms, time-restricted feeding, and healthy aging.“ [00:51:59] Satchin’s recent paper in Cell Metabolism, “Time-Restricted Feeding Prevents Obesity and Metabolic Syndrome in Mice Lacking a Circadian Clock.” [01:00:19] The role of diet in people who lost weight during time-restricted feeding. [01:06:30] “My Circadian Clock,”an app Satchin and his lab at Salk Institute have developed. [01:20:02] Satchin discusses how he convinced his mother to try time-restricted eating. [01:25:32] What Satchin’s diet and eating window looks like on a typical day.  Show notes: [00:03:05] Satchin begins the interview talking about being raised in India and his parents’ expectation that he would become a doctor or engineer. [00:03:46] Satchin talks about his book “The Circadian Code,” which is dedicated to his maternal and paternal grandparents. He touches on how a rapidly evolving modern society disrupts the interconnectedness of our biological rhythms. [00:06:14] Satchin shares how when he was a junior in high school, he lost his father in an accident with a truck driver. [00:07:21] Dawn asks Satchin to talk about how going to agricultural school like his father did cemented Satchin’s interest in science. [00:08:44] Dawn asks how Satchin ended up with a research job at a flavor and fragrance manufacturer in India after finishing his master’s degree. [00:10:10] Satchin talks about what led him to Canada and eventually the U.S. [00:11:21] Ken asks Satchin why he decided to pursue at Ph.D. in plant circadian rhythm. [00:13:41] The circadian rhythm field primarily focuses on understanding the timing mechanism in biological systems like plants, fruit flies, mice and humans.  Satchin discusses how he took a different route and became interested in circadian rhythms and metabolism. [00:15:13] Dawn asks what it is like to work at the Salk institute, a place where Nobel laureates such as Francis Crick once worked. [00:17:11] Satchin talks about his first time-restricted feeding mouse study, which so surprised him that he repeated the study three times. [00:19:03] Ken asks Satchin what he was expecting to learn when he started the mouse studies. [00:20:06] Dawn asks about Satchin’s published findings of his experiments in 2012, which raised the question of whether eight hours was the magic number for time-restricted eating. [00:21:37] Knowing that people go into ketosis after 12 to 16 hours without food, Dawn asks if Satchin has looked at the role of ketosis in time-restricted eating, particularly in regard to weight loss and potential health benefits. [00:22:39] In the mouse studies, the mice that followed time-restricted eating also had an endurance benefit. Dawn asks if Satchin thinks this might also be related to ketosis. [00:25:01] Satchin says in his book, “The moment you eat breakfast, or have your first cup of coffee or tea, is the beginning of your eating window.” Dawn points out that Satchin also says in the book that water doesn’t signal the start of the eating window. She then asks about black coffee, which, like water, has no calories. [00:27:31] Ken asks about the potential use of caffeine to treat jet lag induced by international time-zone travel. [00:29:31] Satchin talks about mouse studies his lab did a few years ago that looked at obesity and type-2 diabetes. [00:30:58] Satchin discusses the point he makes in his book about the dangers of shift work and the importance of sleep. [00:35:11] Dawn asks about a study Satchin is currently undertaking looking at firefighters and shift work. [00:38:10] Numerous studies have shown that time restricted feeding schedules may be able to shift the phase of activity in animals such as mice. Ken asks what Satchin thinks the underlying mechanisms of this may be. [00:40:56] In his book, Satchin mentions that chronotypes — the existence of night owls and morning larks — are largely a myth. Ken asks if we really know whether chronotypes exist or not. [00:44:14] Satchin talks about how he responded when, while at a symposium in Stockholm, a well-respected scientist in the area of obesity came up to Satchin after his talk and said there was no data that shift work causes more disease. [00:45:39] Satchin talks about the importance of darkness when it comes to sleep and our circadian rhythm. [00:48:42] Satchin’s 2017 paper in Aging Research Reviews titled “ Circadian rhythms, time-restricted feeding, and healthy aging.“ points out that circadian rhythms optimize physiology and health by temporally coordinating cellular function, tissue function and behavior. Dawn asks how this study found that optimizing the timing of external cues with defined eating patterns could sustain a person’s circadian clock and possibly prevent disease. [00:51:59] Satchin discusses his mouse study that was detailed in his recent paper in Cell Metabolism titled, “Time-Restricted Feeding Prevents Obesity and Metabolic Syndrome in Mice Lacking a Circadian Clock.” [00:54:59] Ken asks if the benefits of time-restricted feeding reproduced in different mouse strains and across genders, or if all studies been done on the same mouse strain/gender. [00:56:43] Dawn asks if the experimental models using mice, who are nocturnal animals, are presenting difficulties in terms of translating the effects of time-restricted feeding on humans. [00:58:39] Ken asks Satchin for his thoughts on the findings of Joseph Takahashi’s work. Ken wonders if Takahashi’s findings imply that some of the benefits of caloric restriction in mice may actually be due to time restriction. [01:00:19] In Satchin’s human studies, people who had 8- to 12-hour eating windows also had some health benefits and lost weight. Dawn asks what role a person’s diet played in weight loss. [01:03:03] Satchin discusses his thoughts on the translatability of research examining circadian rhythm and inflammatory mechanisms in mice. [01:06:30] Satchin and his lab at Salk Institute have developed an app called “My Circadian Clock,” which is part of a research project that’s using smartphones to track people’s daily behaviors. Dawn asks Satchin to give an overview of the project and discuss how people can participate in the research. [01:09:53] Satchin briefly talks about any potential efficacy in commercial sleep tracking devices. [01:12:08] Satchin talks about the findings of a National Institute of Aging paper that showed time-restricted eating might increase longevity. [01:14:40] Satchin talks about his work with Dr. Valter Longo, who was the guest on episode 64 of STEM-Talk. [01:16:45] While research on chronopharmacology is encouraging, Satchin discusses what some of the main logistical constraints we face in trying to apply its tenets in the clinic. [01:20:02] Satchin discusses how he convinced his mother to try time-restricted eating. [01:23:01] Commenting on how all of Satchin’s mother’s siblings have some sort of metabolic disease, either high cholesterol, diabetes, hypertension or a combination of the three, Dawn asks what is it about the Indian diet that is so unhealthy. [01:25:32] Satchin talks about what his diet and eating window look like on a typical day. [01:26:28] Regarding the symposium Satchin attended in Stockholm. Ken asks how he deals with travel and jet lag in terms of his circadian rhythm. [01:28:27] In terms of the future, Dawn ends the interview asking Satchin what new studies he is considering and what direction he thinks his research will take. Links Salk Institute Dr. Satchin Panda bio “The Circadian Code” My Circadian Clock app Circadian rhythms, time-restricted feeding, and healthy aging Time-Restricted Feeding Prevents Obesity and Metabolic Syndrome in Mice Lacking a Circadian Clock Dr. Valter Longo, who was the guest on episode 64 of STEM-Talk. Learn more about IHMC STEM-Talk homepage Ken Ford bio Dawn Kernagis bio

SEO: Jeff Phillips, Naval Medical Research Unit, University of Alabama, F-22 Raptors, hypoxia, oxygen saturation measurement, arterial gas embolism, aircraft oxygen systems, physiologic episodes, Delores Etter Award, Ken Ford,Dawn Kernagis,Jon Clark,IHMC Today’s interview is with IHMC Research Scientist Dr. Jeff Phillips. Jeff joined IHMC a year ago after spending six years as a research psychologist at the Naval Medical Research Unit in Dayton, Ohio. He worked almost exclusively on hypoxia in tactical aviation and was part of team that was instrumental in getting the F-22 Raptors back into operation after a series of hypoxia-related episodes among jet pilots. In 2012, Jeff won the Dolores Etter Award, which the Department of Navy annually awards to its top performing scientists and engineers. Jeff is a University of Alabama graduate who earned his Ph.D. in experimental psychology. At IHMC, he works on research that ranges from physical and cognitive performance in extreme conditions to the role that ketone esters can play in protecting special operators from hypoxia, fatigue and other issues. Because Dawn Kernagis was in London giving a presentation when we conducted our interview with Jeff, IHMC Senior Researcher Jon Clark joined Ken Ford to co-host the episode. In today’s episode, we discuss: [00:15:45] Jeff’s participation on a team that investigated hypoxia-like episodes F-22 pilots in the Air Force were having. [00:17:02] The problems with aircraft oxygen systems (OBOGs) and the related physiologic episodes (PE) that extend beyond the F-22 to virtually all frontline tactical jet aircraft. [00:18:19] The physiological effects of hypoxia on the brain and the associated cognitive and perceptual performance deficits. [00:19:54] The most promising technologies for detecting a hypoxia event. [00:29:10] The challenge of understanding what may be a multifaceted phenomenon like OBOGS-related PE events. [00:32:30] Studies that have shown pure oxygen in the lungs causes the alveolar cells to collapse. [00:37:10] The possibility that increased breathing (hyperventilation) may be occurring in aircrew involved in PE events who develop rapid onset hypoxia-like symptoms. [00:48:36] The role that mindfulness plays in elite performance as well as day-to-day life. Show notes: [00:06:06] Jeff talks about growing up in Sandflat, Alabama. [00:06:57] Jon asks Jeff what he was like as a kid. [00:07:32] Jeff talks about the impact that reading Stephen Hawking’s “A Brief History of Time” had on him. [00:08:19] Jeff explains how he headed off to the University of Alabama expecting to become a newspaperman, but ended up switching his major to psychology. [00:09:50] Jon asks Jeff about his mentors at Alabama who encouraged him to purse a doctorate in experimental psychology. [00:11:50] Jeff talks about a paper he helped author on handshaking and how it generated so much attention that he was interviewed by the Associated Press and network news shows. [00:14:16] Jon asks Jeff how he ended up at the Naval Aerospace Medical Research Laboratory in Pensacola, Florida. [00:15:02] Ken asks Jeff to describe the work he did at the Pensacola lab. [00:15:45] Jeff talks about becoming part of a team that investigated hypoxia-like episodes F-22 pilots in the Air Force were having when the Pensacola lab relocated to Dayton, Ohio. [00:17:02] Ken points out that problems with aircraft oxygen systems (OBOGs) and the related physiologic episodes (PE) extended beyond the F-22 and affected virtually all frontline tactical jet aircraft. Ken asks Jeff to talk about the how the different military services approached the problem. [00:18:19] Ken asks Jeff about the physiological effects of hypoxia on the brain and the associated cognitive and perceptual performance deficits. [00:19:16] Jon asks Jeff about his participation in studies that assessed different oxygen saturation measurement techniques. [00:19:54] Ken asks Jeff about the most promising technologies for detecting a hypoxia event. [00:21:29] Jon points out that Jeff has been involved in studies that demonstrated a residual cognitive deficit that pilots had following a hypoxic exposure that was still present at two hours after recovering on room air. Jon asks Jeff if he knows why this deficit exists so far after hypoxic exposure. [00:23:41] Jon points out one possible cause of prolonged symptoms is arterial gas embolism causing bubbles in the brain. This is why US aircraft carriers have been recently fitted with hyperbaric chambers to treat aircrew for AGE. The suspected mechanism is sudden pressure fluctuations in the breathing system that is causing over-pressurization to the lungs that some aircrew have experienced. Jon asks Jeff if he thinks that this mechanism could account for prolonged symptoms. [00:024:52] Ken asks if there is a good return-to-duty marker or assessment tool for pilots following a hypoxic exposure. [00:26:14] Jeff gives an overview of the different laboratory-based simulations for studying hypoxia. [00:28:02] Ken asks to what extent pilots in tactical aircrafts are experiencing breathing resistance? [00:29:10] Jeff talks about the challenge of understanding what may be a multifaceted phenomenon like OBOGS-related PE events. [00:32:30] Jon mentions that studies have shown that pure oxygen in the lungs causes the alveolar cells to collapse. He asks Jeff if this is one of the reasons pilots experience hypoxia. [00:35:36] Jon points out that g-forces expose tactical aircraft pilots to atelectasis. He asks if the effects of oxygen atelectasis could increase the potential for hypoxia-like symptoms. [00:37:10] Now that the comprehensive clinical case review has been completed, Ken says it is apparent that aircrew declaring a PE event have developed rapid onset hypoxia-like symptoms at altitudes incompatible with rapid onset hypoxia. Ken asks Jeff if this suggests that increased breathing (hyperventilation) may be occurring in aircrew involved, and can this be addressed with enhanced physiologic training on the consequences of hyperventilation. [00:38:55] Jon asks Jeff to elaborate on his study of emergency oxygen activation based on aircrew symptoms. [00:42:12] Jon mentions that Jeff was recognized by the Navy in 2012 as one of its top performing scientists and engineers. He asks Jeff to talk about the award and the research he was doing that led to the award. [00:44:12] Ken points out that much of the work Jeff has done over the years has been to help people maintain and improve their physical and cognitive performance. He asks Jeff if this played a role in his decision to join IHMC. [00:46:52] Ken asks Jeff about his research into the role that consciousness and mindfulness can pay in people’s lives. [00:48:36] Jon points out that mindfulness plays a role in elite performance as well as day-to-day life. He asks Jeff to talk about the next steps it would take to do proper research on mindfulness in the area of performance and resilience. [00:50:36] Jon points out that neuroplasticity is more easily accomplished in young brains. He asks Jeff how people can keep their brains more plastic as they age. [00:52:27] Jeff talks about the relationship between belief and knowledge and how they can work together to either advance or suppress science. [00:54:38] Jeff ends the interview talking about how his wife and two children live on five acres and that his best ideas often come to him while feeding the chickens or digging fence posts. Links: Jeff Phillips bio Learn more about IHMC STEM-Talk homepage Ken Ford bio Dawn Kernagis bio Jon Clark bio                  

Our guest today is Dr. John Ioannidis, a Stanford professor who has been described by “BMJ” as “the scourge of sloppy science.” Atlantic magazine has gone so far as to refer to him as one of the world’s most influential scientists. John is renowned for his 2005 paper, “Why Most Published Research Findings Are False,” which has been viewed more than 2.5 million times and is the most citied article in the history of the journal PLoS Medicine. He has authored nearly a thousand academic papers and has served on the editorial board of 30 top-tier journals. At Stanford, John is a professor of medicine, of health research and policy, and of biomedical data science in the school of medicine as well as a professor of statistics in the school of humanities and sciences. He is the co-director of the university’s Meta-Research Innovation Center and the former director of the Stanford Prevention Research Center. In today’s wide-ranging interview, John talks about: [00:07:43] What led him to begin questioning the reliability of medical research during his residency at Harvard. [00:12:03] His 2005 paper, “Why Most Published Research Findings Are False.” [00:26:27] How a major issue facing science is a lack of replication. [00:30:51] Which studies are worse, nutritional studies or drug studies. [00:38:25] If it’s possible to remove sampling biases like the healthy user bias. [00:46:50] The need for scientists to disclose their personal dietary biases as well as their personal diets when publishing research findings. [00:52:40] His recent paper, “Evidence Based Medicine Has Been Hijacked,” which argues that vested interests have transformed clinical medicine into something that resembles finance-based medicine. [00:55:36] The impact that funding pressure is having on the veracity of research being done today. [01:08:42] The need for future research to be designed by scientists without vested interests. [01:14:58] The ways John would fix the system if he had magic wand. [01:18:42] And as a bonus, John reads an excerpt from his latest book. Show notes: [00:02:37] Dawn begins the interview asking John about being born in New York but raised in Athens. [00:03:54] John talks about how his parents were physicians and researchers and how they instilled in him a love for mathematics at an early age. [00:05:26] Dawn asks John about winning the Greek Mathematical Society’s national award when he was 19 years old. [00:06:23] John talks about his decision to go to medical school and to attend Harvard. [00:07:43] Ken mentions that John began questioning the reliability of medical school during his residency at Harvard, and asks John to talk about his interest in an “evidence-based medicine” movement that was gathering momentum at the time. [00:08:47] Dawn asks John about his work with the late Tom Chalmers, who played a major role in the development of randomized controlled trials. [00:09:58] John talks about returning to Greece to take a position at the University of Ioannina. [00:12:03] John talks about his 2005 paper “Why Most Published Research Findings Are False,” which became the single most-cited and downloaded paper in the history of the journal PLoS Medicine. [00:15:32] Dawn mentions that when the paper came out, it was theoretical model. She asks John to talk about how now there are a number of studies pointing out problems with preclinical research on drug targets. [00:17:34] Dawn asks John about his decision to leave the University of Ioannina to take a position at Stanford University. [00:21:02] Dawn asks John for his thoughts on ways to improve the peer-review process. [00:24:09] John talks about how he and his colleagues have found that most medical information that doctors rely on is flawed. [00:26:27] Dawn points out that a major issue facing science is a lack of replication. She talks about how funding for repeat studies is hard to come by and that many journals will reject data that replicates previously published work. She asks John for his thoughts about ways to change this. [00:29:14] Ken asks John if he sees interesting variations across disciplines. [00:30:51] Ken follows up with a question about which studies are typically worse: nutritional studies or drug studies? [00:31:28] John talks about the issues with nutritional epidemiology that stems from the often-implausible results arising from food frequency questionnaires. [00:33:04] Dawn mentions that John has talked about the importance of getting nutritional epidemiology right because people are dying from bad decisions. She asks John if we’re at a point where we should scrap all nutritional epidemiological findings. [00:36:20] Ken talks about how John has shown that almost all of the variables in nutritional epidemiology are connected, which partly explains multiple positive results. Ken asks John if there is a way to adjust for that. [00:38:25] Ken points out that many studies proclaim they have adequately adjusted for multiple known health risk factors such as obesity, physical activity, and smoking. Ken asks John if it’s possible to do this in an accurate way in order to remove sampling biases like the healthy user bias. [00:41:21] Dawn mentions that John in the past has said that a way to move forward in nutritional science is to run more large, long-term randomized trials. Considering that the problem is often a lack of behavior change due to the physical and social environment rather than a lack of knowledge about what to eat, she asks John what is the likelihood that large and expensive trials would truly give a meaningful result. [00:44:49] Dawn asks John about the PREMIDED trial, which had originally been characterized as a rigorous and large randomized trial with long-term outcomes, but was later revealed not to be a randomized trial. [00:46:50] Ken asks John about his argument that scientists should disclose their personal dietary biases as well as their personal diets when publishing their research findings. [00:49:24] Dawn talks about the need for the scientific process to be objective, rigorous and ruthless about what is fact and what isn’t. She applauds John for his work that has shown how easy it is for researchers to manipulate data and results, and asks him to talk about the ways research is being manipulated. [00:52:40] Dawn asks John to talk about his paper, “Evidence Based Medicine Has Been Hijacked,” which makes the argument that vested interests have transformed clinical medicine into something that resembles finance-based medicine. [00:55:36]Dawn talks about how intense competition for funding has led to an aggressive environment where scientists are tempted to skew their findings to influence future funding. She asks John for his thoughts on the impact that funding is having on the veracity of research being done today. [00:56:59] Ken asks John to elaborate on his comments that the healthcare system has become a threat to human health. [00:58:39] John shares some ideas about ways to fix the healthcare system. [00:59:39] Ken mentions an article John wrote that described how the biomedical research community has promoted the idea that genetics coupled with information technology will improve and transform healthcare and human health. Ken asks John to talk about why he thinks this approach has largely failed, and also talk about his proposal for a wholesale reevaluation of biomedical research. [01:02:49] John talks about his research into “hyper-prolific” authors. [01:06:13] Dawn brings up the need for universities to do a better job educating future scientists on ways to design studies and recognize biases. She asks John if he thinks we’re making progress in this area. [01:08:42] Dawn points out that John in the past has talked about the entrenched bias in research and the need for future research to be designed by those without vested interests. She asks John if there’s a realistic way for researchers to balance expertise versus bias. [01:10:39] Ken says it seems that the research enterprise is currently following a model of “product control,” that is, assessing the research once it has been finished and written up. He adds that this model coupled the reality of “publish or perish” thinking seems to be driving a lot of the problems we’re seeing with research quality and replication. Ken asks John how do we move from a “product control” model to more of a “process control” method in science, as is used in manufacturing, to ensure that the finished product is good by default. [01:13:11] Dawn points out that there’s an increasing number of journals, including open access journals, and that this may lead to lower-quality research findings being published. She asks John for his thoughts. [01:14:58] John talks about ways he would fix the system if he had magic wand to wave at the problem. [01:17:29] Dawn points out that John has been writing literature since he was eight years old and has published seven books. She asks John about the role writing has played in his life. [01:18:42] John ends the interview reading an excerpt from his latest book. Links: John’s Stanford faculty bio List of John’s published research John’s Wikipedia page Atlantic article about Ioannidis Why Most Published Research Findings Are False Evidence-based Medicine Has Been Hijacked What Happens When Underperforming Big Ideas in Research Become Entrenched Learn more about IHMC STEM-Talk homepage Ken Ford bio Dawn Kernagis bio

Today’s episode features Dr. Dava Newman, the first female engineer to serve as NASA’s deputy administrator. Dava  is currently the Apollo Professor of Astronautics at the Massachusetts Institute of Technology. For more than 20 years, she has worked passionately to figure out what it will take to put humans on Mars. She is perhaps best known, however, for developing a next-generation spacesuit called the BioSuit, a slim-fitting compression suit that’s designed to make it easier for astronauts to move around on lunar surfaces. Dava joined the faculty at MIT in 1993 and served as NASA’s deputy administrator from 2015 to 2017. She also is on the faculty of the Harvard–MIT Health, Sciences, and Technology department. As the director of MIT’s Technology and Policy Program from 2003 to 2015, she led the institute’s largest multidisciplinary graduate research program with more 1,200 alumni. She is the author of “Interactive Aerospace Engineering and Design,” an introductory engineering textbook, and has published more than 300 papers. Links to Dava’s book, papers and bio, as well as videos of the BioSuit, are included at the bottom of the show notes. In today’s interview with Dava, we discuss: [00:03:01] Her memories of watching the Apollo Moon landings as a child. [00:06:36] How Dava made the Notre Dame women’s varsity basketball team as a walk-on. [00:09:49] Her work over the past 20 years to get people on Mars. [00:11:19] Dava’s thinking behind the design of a slim-fitting spacesuit. 00:15:12] The physiological monitoring systems she would like to see incorporated into next-generation spacesuits. [00:26:00] How she thought the call from the White House about the NASA position was a prank. [00:27:06] Dava’s takeaways from her four space missions to measure astronaut performance in microgravity. [00:28:41] Her transition back to MIT after her stint as NASA deputy administrator. [00:38:42] Dava’s advice for today’s young aspiring scientists and engineers, a group she says will become known as the Mars generation. Show notes: [00:02:30] Dawn begins the interview by asking Dava to elaborate on comments she has made about having the best job in the world. [00:03:01] Dawn asks Dava about growing up in Montana during the Apollo years and watching the moon landings on TV. [00:03:43] Dava talks about her years in middle school and high school. [00:04:17] Ken asks Dava about her decision to attend Notre Dame. [00:05:40] Dava talks about how she was often the only women in her science and engineering classes back in the early 1980s. [00:06:36] Dawn asks Dava about making the Notre Dame women’s varsity basketball team as a walk-on. [00:08:30] Dawn asks Dava about her decision to write an introductory aerospace engineering textbook shortly after accepting a faculty position at MIT. [00:09:49] Dava talks about how her goal of getting people to Mars has been a passion of hers for the past 20 years. [00:11:19] Ken points out that Dava is perhaps best known for designing a slim-fitting spacesuit call the BioSuit. Ken asks Dava what motivated her to redesign spacesuits. [00:13:38] Dawn asks Dava what human bio-energetic requirements will look like for lunar surface operations and how they differ from current EVA operations? [00:15:12] Dawn asks Dava about the physiological monitoring systems she would like to see incorporated into next generation spacesuits. [00:17:09] Dava talks about how spacesuit design has faced significant biomedical challenges, particularly for women. [00:21:30] Ken mentions that Dava wrote the proposal for the BioSuit while on a sailing trip during a sabbatical, and follows up by asking her to tell the story of how she and her husband became stranded in the middle of the Pacific. [00:26:00] Dava explains that when she got a call from the White House about becoming the deputy administrator for NASA, she thought the phone call was a prank. [00:27:06] Dawn points out that Dava has flown four space experiments to measure astronaut performance in microgravity. Dawn asks Dava what stands out in terms of those experiences. [00:28:41] Dava talks about her transition back to MIT after her time as NASA deputy administrator. [00:31:09] Ken asks Dava for her thoughts on the Space Launch System, a space shuttle-derived super heavy-lift expendable launch vehicle. [00:32:21] Ken talks about InSight, a robotic lander that has been designed to study the interior of Mars and is expected to land on the planet in time for Thanksgiving. Ken asks Dava to give an overview of the mission and how it might lead to a new understanding of Mars. [00:35:05] Dava talks about how in addition to Mars, teaching is another one of her passions and that she is particularly interested in getting more women and people of color into science. [00:37:29] Dawn asks Dava about her role models who helped guide her career path. [00:38:42] Dava ends the interview talking about how young people today, especially teen-agers, will become known as the Mars generation, the first generation to walk on Mars, and offers advice for aspiring scientists and engineers. Links: Dava’s MIT bio Dava’s NASA bio Dava’s Wikipedia page TED video: How to create a Spacesuit Adam Savage interview with Dava Amazon: “Interactive Aerospace Engineering and Design” Learn more about IHMC STEM-Talk homepage  Ken Ford bio Dawn Kernagis bio

Today’s guest today is Rob Mueller, one of NASA’s senior technologists who is leading an effort to establish a base station on the Moon, and eventually Mars, as well as other destinations in the solar system. Rob is the senior technologist for the Advanced Projects Development at NASA Kennedy Space Center and a co-founder of Swamp Works, an innovation lab that has brought together NASA engineers, researchers and scientists to work on creating Spaceports across the solar system. As most of our listeners know, NASA has been working toward an eventual mission to Mars. But before venturing to Mars, NASA first plans to build a lunar base on the Moon. In announcing the agency’s decision to return to the Moon, NASA Administrator Jim Bridenstine said that this time the agency isn’t interested in just leaving flags and footprints on the lunar surface. “This time when we go, we’re going to go to stay,” he said. As part of this mission, Rob’s work is particularly focused on ways to excavate and mine the resources of space so that astronauts and eventually others will be able to live off the land in space. In today’s interview, Rob talks about his nearly 30-year career with NASA as well as the future of space exploration. Topics we cover include: [00:12:40] In order to survive and thrive in space, we need to be able to build things in space. [00:14:51] Rob’s lab at NASA called Swamp Works. [00:18:44] Swamp Works’ goal of expanding civilization into the solar system. [00:20:33] The Regolith Advanced Surface Systems Operations Robot project. [00:24:59] How there are billions and billions of times the resources in outer space than here on Earth, and our potential to excavate these materials. [00:30:41] The Lunar Orbital Platform-Gateway. [00:35:29] NASA’s decision to return to the Moon before venturing to Mars. [00:37:33] How new technologies being developed for Spaceflight could eventually have applications on Earth as well. [00:40:29] How to survive and thrive on the Moon and Mars, we will need to be able to build landing pads, habitats and roads. [00:49:03] A partnership Swamp Works has with Astrobotic to develop a micro-rover. [00:51:11] How the regolith of the Moon, Mars and other planets as well as asteroids contain valuable resources. [00:54:12] The future of space exploration. [00:57:16] How Rob responds to people who question the cost and relevance of going to the Moon and beyond. [01:02:13] And if people are a little less likely to take Rob’s phone call given that there’s a Robert Mueller in Washington who’s conducting a Russian investigation. Show notes:  [00:03:26] Rob talks about growing up in Portugal and how Rob ended up with an international background as a kid because of his father’s work. [00:04:00] Dawn asks Rob if it’s true that as a 12-year-old he was a pioneer of surfing in Portugal. {00:04:40] Rob talks about how his interest in advanced technology led him to the states and the University of Miami after graduating from high school. [00:06:48} Rob describes how he graduated from Miami shortly after the Challenger accident and ended up applying for a job at NASA. [00:07:56} Ken points out that it was an O-ring on the Solid Rocket Boosters that failed to maintain a seal that led to the Challenger explosion. Ken asks Rob to talk about how he came to work on the Solid Rocket Boosters when NASA hired him in 1989. [00:10:09] Rob talks about he actually was more interested in robotics than space when he went to work at the Kennedy Space Center. [00:11:02] Dawn asks Rob about his decision to work on an MBA at the Florida Institute of Technology while he was working at NASA. [00:11:45] Dawn follows up with a question about how Rob ended up in the Netherlands studying for a master’s degree in internal space systems engineering. [00:12:40] Dawn points out that Rob has been at NASA for nearly 30 years and that he is often quoted as saying that if we are going to survive and thrive in space we need to be able to build things in space. She asks Rob to explain what he means by that. [00:14:51] Rob talks about his lab at NASA, called Swamp Works, and how the lab is trying to foster a more innovative environment at the space agency. [00:17:43] Dawn asks Rob how he came up with the name Swamp Works. [00:18:44] Rob mentions that a goal of Swamp Works is to expand civilization into the solar system. Dawns asks him to talk about what that means. [00:20:33] Ken points out the Rob is the lead technologist for the Regolith Advanced Surface Systems Operations Robot project, and asks Rob to talk about his work in this area. [00:24:59] Ken mentions that Carl Sagan was known to say that there are billions and billions of times the resources in outer space than here on Earth. Ken asks Rob to talk about the potential and possibilities that our ability to excavate these materials will provide. [00:27:56] Dawn talks about how we will need new technologies if we’re going to survive and thrive in space. She asks Rob about 3D printing, which is a good example of one of the technologies that could, with further development, completely change the game. [00:30:41]A few years ago, an asteroid mission was the official destination of NASA with respect to human spaceflight.  Ken mentions that many of NASA’s current plans for the future of human spaceflight are focused on development of what is currently referred to as the Lunar Orbital Platform-Gateway. Ken asks Rob to describe the Gateway and the rationale for its construction. [00:35:29] Mars remains the long-term goal for human spaceflight. But from an engineering and budgetary perspective, Ken says it seems more logical to first return to the moon and that, indeed, the conversation within the agency has shifted back to the Moon. In announcing the agency’s decision to return to the Moon, NASA Administrator Jim Bridenstine said that this time the agency isn’t interested in just leaving flags and footprints on the lunar surface. “This time when we go,” he said, “we’re going to go to stay.” Ken asks Rob to talk about this promising development. [00:37:33] Dawn mentions that IHMC is working with NASA on designing an exercise machine for human Spaceflight beyond LEO (low-Earth orbit). NASA has known for a long time that astronauts on long-duration spaceflights lose muscle strength and mass as well as bone density because their bodies spend so much time in microgravity. Dawn says that one aspect of this project is that it could end up developing a whole new way of resistance training not only for space flight, but also for here on Earth. She asks Rob if the new technologies for space that he’s working on could also eventually have applications on Earth as well. [00:40:29] To survive and thrive on Mars, we will need to be able to build landing pads, habitats and roads. Dawn asks Rob to talk about the work that’s being done in this area. [00:42:42] In addition to the civil engineering requirements that will be needed to enable a sustainable presence on the Moon and eventually Mars, Ken says it makes sense to “live off the land” to the extent possible. In particular, insitupropellant production on the Moon, says Ken, seems intriguing. But given that it can take billions of dollars up front and years to deploy the infrastructure required to produce industrial levels of cryogenic propellants on the moon, Ken asks how can we ever get to the point where we have reusable systems using insituresources when it’s so much cheaper and faster just to use Earth-supplied expendable systems? [00:49:03] Dawn asks Rob about a partnership Swamp Works has with Astrobotic to develop a micro-rover. [00:51:11] Ken talks about how on Earth, regolith includes soil, which is a biologically active medium and a key component in plant growth as well as life on Earth. Although regolith also appears on the surfaces of the Moon, Mars and other planets as well as asteroids, their surfaces do not contain soil. But their surfaces do contain other valuable resources. Ken asks Rob to talk about this. [00:54:12] Dawn asks Rob to talk about the future of space exploration. [00:57:16] In the just-released movie “First Man,” which is about NASA’s mission to put a man on the moon, there are several scenes of politicians and demonstrators protesting the financial and human cost of going into space and traveling to the moon. She asks Rob to talk about how he responds to people who question the cost and relevance of going to the Moon and beyond. [01:02:13] Given the current Russian investigation that’s being conducted by Washington’s Robert Mueller, Dawn asks Rob if people are a little less likely to take his phone calls these days.   Links: Rob Mueller NASA bio Rob Mueller LinkedIn page Swamp Works home page NASA home page Video: NASA experiments with 3D-printing robots The Verge: How NASA plans to use lunar dust to build structures on the Moon Learn more about IHMC STEM-Talk homepage Ken Ford bio Dawn Kernagis bio      

Today’s guest is a science journalist and author who has written extensively about the pharmaceutical industry. Robert Whitaker is also the founder of Mad in America, a nonprofit organization that focuses on getting people to rethink psychiatric care in the United States. As you will learn in today’s episode, one in six Americans takes a psychiatric drug. More than 130,000 children under the age of five are taking addictive anti-anxiety drugs prescribed by doctors. Whitaker has spent most of his career focused on changing the current drug-based paradigm of psychiatric care in the U.S. He has written three books about the pharmaceutical industry and the psychiatric profession. He has looked at how drugs used for depression, bipolar disorder and schizophrenia are causing a spike in America’s disability numbers. He also has investigated the history of medications prescribed for these disorders, how they are marketed, and why they’ve grown in popularity. Discover magazine named Whitaker’s first book, “Mad in America,” one of the best science books of 2002. His second book, “Anatomy of an Epidemic,” won the 2010 Investigative Reporters and Editors book award for best investigative journalism. His third book, “Psychiatry Under the Influence,” is a textbook used in university classrooms around the country. In today’s interview, we discuss: [00:11:08] When Robert first became disillusioned with the pharmaceutical industry [00:16:53] How Robert’s investigation into schizophrenia in the U.S. led him to write his first book,  “Mad In America.” [00:26:58] Why the U.S. has seen such a sharp increase in the number of disabled, mentally ill people since the advent of psychotropic medications. [00:45:10] How many drugs may have efficacy in clinical trials over the short term, but overwhelming evidence shows over the long term many medications actually increase a person’s risk of becoming chronically ill and functionally impaired. [01:00:43] Robert’s investigation into the FDA’s review of studies that looked at Prozac [01:03:38] Antidepressants and their side effects. [01:08:40] How concerns over ADHD have led to an alarming percentage of children, especially boys, being drugged for exhibiting what once considered normal or at least acceptable behavior. And much more. Show notes:  [00:02:24] Robert talks about growing up in Denver and taking family vacations around the country. [00:03:48] Robert explains how in high school he was so convinced he was going to attend Stanford University that he didn’t bother to apply to another college. [00:05:48] Dawn mentions that Robert graduated with a degree in English literature and after college decided he wanted to lead a life of adventure. Dawn asks him where that career path took him. [00:07:11] Robert talks about abandoning his dream of becoming a novelist and taking a job at a small newspaper in upstate New York. [00:08:51] Dawn points out that Robert eventually went to work for a newspaper in Albany, N.Y., where he became a medical writer. She asks him about the year he spent as a Knight Science Journalism fellow at MIT. [00:09:50] Ken asks Robert about moving to Boston and becoming director of publications at Harvard Medical School. [00:11:08] Robert talks about co-founding CenterWatch, a publishing company focused on the business of clinical drug trials. He describes how he became disillusioned with the pharmaceutical industry because it seemed to him that clinical trials had become so commercialized that they were corrupting the testing of new drugs. [00:13:44] Ken mentions that during this period, Robert came upon information about abuses of psychiatric patients in research settings. Ken asks Robert to share how he took this information and went to the Boston Globe to propose a newspaper series. [00:16:53] Dawn describes how the work Robert did for this series in the Boston Globe led him to information that schizophrenics in the U.S. were faring worse than patients in the world’s poorest countries. Dawn asks Robert to talk about how this information led him to write his first book, “Mad In America.” [00:19:42] After “Mad In America,” Robert became convinced that much of the information medical professionals were sharing with the mainstream press was out of sync with the science. Robert describes a scene in the movie “A Beautiful Mind” that he says illustrates this sort of misinformation. [00:21:43] Ken asks Robert about the criticism he received after the publication of “Mad In America.” [00:23:30] Dawn mentions that even though Robert had decided not to write another book about psychiatry, he started looking at disability numbers and became curious as to why there was an extraordinary rise in the number of people in the U.S. going on disability. Dawns asks Robert about the book that came about because of that curiosity, “Anatomy of an Epidemic.” [00:26:58] Ken points out that the book investigates why the U.S. has seen such a sharp increase in the number of disabled, mentally ill people since the advent of psychotropic medications.  Ken asks Robert about the mix of causes that has led to this increase. [00:35:00] Ken says that it seems that psychiatry’s expanded diagnostic boundaries have meant that many more people are deemed mentally ill. Ken points out that almost anyone can identify themselves in the voluminous “Diagnostic and Statistical Manual of Mental Disorders,” which runs something like 950 pages and describes more than 300 maladies.  Ken asks Robert if just being human is enough for people to identify themselves somewhere in the book. [00:43:33] Ken asks Robert about the financial disincentives to go off disability and return to work. [00:45:10] Dawn asks Robert to talk about how drugs may have efficacy in clinical trials over the short term, but there is overwhelming evidence that over the long term these medications actually increase a person’s risk of becoming chronically ill and functionally impaired. [00:52:29] Ken asks Robert about the textbook he co-wrote, “Psychiatry Under the Influence,” which takes a deep dive into the behavior of the American Psychiatric Association. [00:57:57] Dawn asks Robert about the clinical trials for alprazolam, which Upjohn eventually marketed as Xanax. She asks Robert about the problems the drug created that never seemed to make it into the mainstream media. [01:00:43] Dawn asks Robert about his investigation into the FDA’s review of studies that looked at Prozac. [01:02:15] Ken mentions that after Prozac, Pfizer created sertraline, which is sold as Zoloft. Ken asks Robert to talk about how Zoloft failed to produce a better result than a placebo in four of the six trials that Pfizer submitted to the FDA. [01:03:38] Dawn asks Robert to talk about antidepressants and their side effects. [01:05:56] Ken points out that Robert has often commented that if you pour antidepressants into a society the way we do in the U.S., thatyou can expect an increase in violence and homicides. Ken asks Robert to expand on this. [01:08:40] Ken says it seems we have an epidemic of ADHD and that an alarming percentage of children, especially boys, seem to be drugged for exhibiting what was once considered normal or at least acceptable behavior.  There have always been kids who were rowdy, says Ken, boys who couldn’t sit still, goofed off or displayed other less than ideal behaviors. But, Ken adds, we did not drug them, and the vast majority turned out just fine.  Ken asks Robert if he has looked into this. [01:12:08] Dawn wraps up the interview by asking Robert if he has finally followed his agent’s advice to not write another book about psychiatry, or if he is working on another one. Links: Mad in America website Robert Whitaker bio “Mad in America” book “Anatomy of an Epidemic” “Psychiatry Under the Influence” Robert Whitaker Amazon page Learn more about IHMC STEM-Talk homepage Ken Ford bio Dawn Kernagis bio      

Nearly 60,000 Americans are diagnosed with Parkinson’s disease every year in the U.S. The disease is an incredibly complex disorder that affects more than 10 million people worldwide. Our guest today is Dr. Michael Okun, who is considered the world’s foremost authority on the treatment of Parkinson’s.He is the Adelaide Lackner Professor and Chair of Neurology at the University of Florida Health College of Medicine as well as the co-director of the university’s Fixel Center for Neurological Diseases. The center is known for its interdisciplinary faculty that provides a one-stop, patient-centered clinical research experience that attracts patients from around the world. Since 2006, Michael has been the National Medical Director for the Parkinson’s Foundation and works very closely with a wide range of organizations such as the Michael J. Fox Foundation. The American Society for Experimental Nuerotherapeutics recently awarded Michael the 2018 Presidential Award.  In 2015, he was recognized during a White House ceremony by the Obama administration as a “Champion for Parkinson’s Disease.” Michael also is an accomplished writer with more than 400 peer-reviewed articles and even a book of poetry. In today’s episode, we discuss: [00:17:56]What Parkinson’s disease is and the wide range of symptoms that can arise as a result of the disease. [00:29:19] How Parkinson’s disease is diagnosed since there is no specific test that can diagnose the disease. [00:32:11] The common risk factors associated with neurodegenerative disease. [00:38:20] The actor Alan Alda’s recent announcement that he has been living with Parkinson’s for more than a year. [00:41:04] A UCSF study that looked at the prevalence of Parkinson’s among veterans who had experienced traumatic brain injury. [00:46:32] Treatments that are available for Parkinson’s. [00:55:57] The cognitive, behavioral and mood effects of deep-brain stimulation. [01:17:11] The potential use of brain prosthetics or orthotics in patients with neurological disease. [01:29:26] Whether Parkinson’s therapy is moving toward local, systemic or a combination of the therapies. [01:31:48] The relationship between metabolism and nutrition and the progression of Parkinson’s disease. And much more.  Show notes: [00:02:53] Michael begins the interview taking about growing up in West Palm Beach, Florida, and his love of baseball and collecting baseball cards. [00:03:39] After high school, Michael decided to attend Florida State University and focus on a liberal arts education. Dawn asks Michael if it’s safe to assume he wasn’t thinking about medical school when he started college. [00:04:53] Dawn asks Michael how a history major ultimately decides to become an MD. [00:06:18] Ken asks Michael to elaborate on a funny story about how he ended up going to the University of Florida for medical school. [00:10:10] Michael talks about how went to med school thinking he wanted to be a black-back family practitioner, but became so interested in neurology that he changed his mind. [00:13:06] Ken mentions that during Michael’s time at Florida, he became fascinated by what was going on in the brain of people who had tremors. Ken asks Michael if that is what led him to focus on Parkinson’s disease during his postdoc at Emory? [00:17:56] Even though most people are familiar with images of people like Michael J. Fox and Mohammed Ali who have tremors, most people aren’t aware that Parkinson’s has a wide range of symptoms, which makes it an incredibly complex disease. Michael gives an overview of Parkinson’s and the various symptoms that can arise as result of the disease. [00:22:29] Since Parkinson’s is such a remarkably complex and multi-system disease, Ken asks Michael how he integrates the different clinical disciplines that are required to treat someone with Parkinson’s. [00:29:19] Ken mentions that there is no specific test to diagnose Parkinson’s, and asks Michael if the disease is primarily diagnosed by symptoms. [00:32:11] Dawn mentions that when people are diagnosed with Parkinson’s, it means they don’t have Alzheimer’s or ALS. However, neurodegenerative diseases often have common risk factors such as type 2 diabetes or environmental exposures or trauma, as well as a neuroinflammatory or oxidative stress component. Ken asks what makes these diseases different beyond the specific areas of brain anatomy that they affect, and why might somebody with a given set of risk factors get one rather than the other? [00:38:20] Dawn mentions that more than a million people in the U.S. have Parkinson’s, including actor Alan Alda, who announced in July that he has been living with the disease for more than a year. In announcing he had the disease, Alda stressed that he has been living a full and happy life. As the national medical director for the Parkinson’s Foundation, Michael often stresses that people with Parkinson’s can lead happy and healthy lives, and Dawn asks Michael to talk about that. [00:41:04] Ken mentions a UCSF study in the online issue of Neurologythat looked at the prevalence of Parkinson’s among veterans who had experienced a traumatic brain injury. The study found that these veterans faced a 56 percent increased risk for Parkinson’s. Ken asks Michael to talk about the study and its implications behind a military population. [00:44:35] With a growing understanding of repeat TBI and CTE, Dawn talks about how we are learning that there is a link between brain injury and neurodegenerative pathology. She asks Michael if we have any idea as to why there is a link between TBI and neurodegeneration? [00:46:32] Michael gives an overview of the treatments that are available to treat Parkinson’s. [00:52:39] Dawn asks Michael to talk about the current state of biomarkers for tracking the progression of Parkinson’s and tracking the response to a disease-modifying intervention. [00:55:57] Dawn points out that Michael has had a prolific career as a researcher exploring non-motor basil ganglia brain functions. He also has helped pioneer studies exploring the cognitive, behavioral and mood effects of deep brain stimulation. She asks Michael to give listeners an overview of deep brain stimulation, also known as DBS. [01:00:35] Ken asks Michael to talk about the primary mechanism of action of DBS. [01:05:09] Michael discusses DBS’s dark past and how the intervention’s reputation has recently rebounded. [01:10:53] Dawns asks what kind of patient is a good candidate for DBS. [01:12:42] Michael talks about autonomic nervous system symptoms in Parkinson’s disease. [01:14:40] Dawn wonders about other forms of non-invasive nervous system stimulation and asks if approaches such as transcutaneous vagal nerve stimulation have shown an impact on Parkinson’s disease or Parkinson’s symptoms. [01:17:11] Ken points out that researchers at IHMC often work toward development of AI software systems intended as cognitive orthotics aimed at amplifying and extending human cognition. He asks Michael about the potential use of brain prosthetics or orthotics in patients with neurological diseases and what opportunities Michael sees to better understand the brain and brain networks. Ken also asks about the ethical challenges involved in such technology and who should be operated on. [1:20:32] Dawn mentions that one arm of research for Parkinson’s treatment is developing vaccines or other approaches to aid in the removal of alpha-synuclein protein aggregation. Similar approaches have so far failed with the analogous approach to beta-amyloid in Alzheimer’s disease, where the amyloid burden also doesn’t directly correlate with disease progression or severity. Dawn asks if there is evidence that this might be a more successful approach in Parkinson’s. [01:25:07] Ken brings up that stem cells are often mentioned in the context of Parkinson’s and asks Michael about the prospects. [01:28:08] Dawns asks about editing certain genes in situ with a CRISPR-Cas9. [01:29:26] Ken points out that PINK1 is involved with the ubiquitin pathway, and that LRRK2 is involved with the immune response. Ken asks if a systemic approach to treatment is more promising than a local treatment. He also asks if Parkinson’s disease therapy is moving toward local or systemic treatment or a combination of the therapies. [01:31:48] Dawn asks if there are known relationships between metabolism and nutrition and the progression of Parkinson’s disease or its symptoms. [01:33:21] Dawn talks about how the Obama administration recognized Michael during a White House ceremony in 2015 and how earlier this year the American Society for Experimental Neurotherapeutics honored Michael with its Presidential Award. Dawn asks Michael to share what that was like. [01:34:40] Dawn ends the interview by asking Michael about his passion for writing. She points out that Michael received a scholarship for creative writing in school and that today he has more than 400 peer-reviewed articles and has also written a book of poetry. Dawn asks Michael to talk about the role that writing has played in his life. Links Michael’s UF Department of Neurology faculty page Michael’s papers on PubMed IHMC talk on “Parkinson’s Disease: The Latest Advances in Treatment and Research.” IHMC talk on “Parkinson’s Treatment: 10 Secrets to a Happier Life” UF’s Movement Disorders and Neurorestoration Program “Parkinson’s Treatment: 10 Secrets to a Happier Life” “10 Breakthrough Therapies for Parkinson’s Disease” “Ask the Doctor About Parkinson’s Disease” “Lessons From the Bedside” Learn more about IHMC STEM-Talk homepage

Today’s episode features a timely interview with Google’s Director of Research, Peter Norvig.  He is also the co-author of “Artificial Intelligence: A Modern Approach,” which is in its third edition and is a leading AI textbook. In today’s interview, we talk to Peter about fake news, trolls, self-driving cars, killer robots, the future of artificial intelligence, and a lot more. We also talk to Peter about digital privacy. Tech companies such as Google, Facebook, Twitter and others have been facing heavy criticism recently over the way they handle people’s digital data. In May, Europe began enforcing a new law that restricts how people’s online data is obtained and used. In June, California passed a privacy law that requires tech and information companies to share how they’re collecting people’s data and how they’re sharing that information.  At the moment, Congress is considering a federal privacy law that also covers how personal digital data is handled. Ken and Peter have a history that goes back to their days at the NASA Ames Research Center in Silicon Valley. Ken was the center’s associate director at the time and recruited Peter to become the center’s chief of the Computational Sciences Division. In today’s episode, we discuss: How artificial intelligence has changed since the days when Peter first became a practicing AI professional. [00:19:20] How AI research is now increasingly driven by commercial interests rather than government grants. [00:23:39] What deep learning is and what the word “deep” means in this context. [00:27:48] The philosophical questions that surround AI, such as: “What does it mean to be intelligent?” and “Can a machine be conscious?” [00:36:58] Search function and privacy. [00:44:32] Google’s responsibility for the content posted on their platforms. [00:50:06] The problems that arise when tech companies police content. [00:51:17] Peter’s thoughts about a meeting Elon Musk had with U.S. governors where he urged them to adopt AI legislation before “robots start going down the street killing people.” [00:56:18] The meaning of “singularity” and whether Peter believes in it. [01:03:19] Peter’s advice for listeners who are interested in going to work for Google someday. [01:12:10] Show notes: [00:02:15] Dawn begins the interview asking Peter about an interview he did with FORBES magazine where he said, “I don’t care so much whether what we are building is real intelligence. We know how to build real intelligence. My wife and I did it twice, although she did a lot more of the work. We don’t need to duplicate humans, that’s why I focus on creating tools to help us rather than duplicating what we already know how to do. We want humans and machines to partner and do what humans and machines couldn’t do on their own.” Dawn asks Peter to expand on this belief and how it influenced his career. [00:03:23] Dawn asks Peter about growing up in Boston and his habit of writing the local newspaper to complain about innumeracy and the sloppy language in its science stories. [00:04:36] Ken mentions Peter’s father was a math professor and his mother an English literature professor. While in high school, even though teachers suggested a career in journalism, Peter decided to learn programming instead. Peter talks about how he also took a class in linguistics, which led him to start thinking about using computers to process natural language. [00:05:54] Dawn asks Peter about classes he took at Brown University that led him to start thinking about artificial intelligence. [00:07:00] Dawn mentions that Peter went to the University of California Berkeley for his Ph.D. and asks him what motivated him to enroll in the computer science department and research AI. [00:08:03] Dawn asks Peter about the research he did after receiving his Ph.D. and becoming an assistant professor at University of Southern California as a research faculty member. [00:08:36] Peter talks about the work he did in various labs during the early years of his career. [00:09:45] Peter talks about how Ken, while on leave from IHMC, recruited Peter in 1998 to become the division chief of the Computational Sciences Division at NASA Ames. [00:11:32] Ken and Peter recall a tag-team address they made at the 1999 conference of the Association for the Advancement of Artificial Intelligence. The talk was titled, “AI and Space Exploration: Where No Machine Has Gone Before”. [00:14:07] Dawn mentions that in 1996 a couple of Stanford students developed a search algorithm that was originally known as “Back Rub,” which eventually led to the formation of Google in 1998. Peter joined Google in 2001 and Dawns asks how that came about. [00:16:11] Dawn asks Peter to talk about the differences in the work cultures of Google and NASA. [00:17:41] Ken mentions that the textbook Peter co-wrote with Stuart Russell is now in its third edition since its original publication in 1995, and that it is considered one of the leading textbooks on artificial intelligence. Ken asks if Peter is considering a new version of the textbook in the face of the fast evolution of the field. [00:19:20] Dawn comments on how AI programming itself has changed over time with the iteration of new languages, tools, and communities. She asks how things are now different for the practicing AI professional, compared to when Peter was getting started. [00:21:28] Ken asks if Peter has any thoughts on the relationship between reality and some of the inflated expectations that arise from the current overhyping of AI that has stoked fears as well as utopian dreams. [00:23:39] Because AI is now increasingly being driven by commercial interests rather than government research grants, Dawn asks how the field will change. [00:25:10] Dawn asks why the look and feel of Google web searches hasn’t changed that much over the past 10 years. [00:26:09] Dawn mentions that Google’s search engine has flourished for 20 years because of its speed, relevance, coverage, and other such measures of performance. Given that Google is still the gold standard in search, she asks how Google tests for performance. [00:27:48] Ken mentions that about a decade ago Google was slightly disparaging about the utility of AI, but then Google started to suddenly change its tune, at least that’s how it looked from the outside. Ken comments that this seems to be because of the sudden explosion of applications of deep learning which, when applied to very large data, yield numerous state-of-the-art results in domains such as speech recognition, image recognition and language translation. Ken asks Peter to explain what deep learning is, what it does well, and what the word “deep” means in this context. [00:36:58] Ken comments on how, back in the day, good old-fashioned AI raised many big philosophical questions. Questions ranged from “What does it mean to be intelligent?” to “Can a machine be conscious?” Many of these questions were explored in famous films such as “Blade Runner,” and “Ex Machina.” Ken and Peter talk about whether there are new big questions being raised in the context of newer forms of AI. [00:39:41] Ken brings up how he and Pat Hayes developed an award in the ‘90s that they called the Simon Newcomb Award that recognized the most wrong-headed arguments against the possibility of intelligent machines. [00:41:25] Ken observes that the papers at the National AI Conference, while often technically excellent, are typically statistical in nature and narrowly cast. Ken goes on to propose that this could be a sign of the field maturing, or perhaps ducking the hard and interesting questions, or a bit of both. He asks Peter for his thoughts on this. [00:44:32] Ken brings the conversation back to Google and asks about search function and privacy. He mentions that Google provides some of the web’s most used and appreciated software, including Gmail, Docs, Drive, Calendar, and more. But given Google’s access to vast amounts of data that has led to personalized searches and advertisements, Ken asks Peter for his thoughts about the concerns regarding loss of privacy and the use of personal information. [00:47:45] Dawn asks Peter how Google recommends news articles based on people’s recent searches. Dawn says that some people argue that sending people news articles based on their history is not such a good thing. [00:50:06] Dawn asks Peter if Google feels as if it has any kind of responsibility to weed out fake news and international trolling. She also asks if the controversies about fake news and trolls are beginning to muddle the definition of information itself. [00:51:17] Ken mentions that problems are arising for platform providers not so much because of legal reasons but because of ideological reasons. Providers are now deciding to police content that comes onto their site and ban one group of ideological crazy people while not addressing another equally unhinged group.  Ken asks Peter how society will construe the role of Google, Facebook and others as they work to police the content that appears on their sites. [00:55:31] Dawn asks Peter for his take on companies such as Powerset as well as others who see natural language search, which allows people to use sentences rather than keywords, as the future of search. [00:56:18] Dawn mentions how last year she turned the tables on Ken and interviewed him for STEM-Talk on episodes 49 and 50. In one interview she asked Ken about a New York Times story that referenced the meeting Elon Musk had with governors where Musk said that they should adopt AI legislation before “robots start going down the street killing people.” She asks Peter if he ascribes to this killer AI theory. [00:59:03] Ken comments on how interesting he finds the sudden change in the arguments, which has evolved from pundits saying AI was provably impossible to now saying that superhuman AI represents the greatest danger ever faced by the human race. [00:59:49] Dawn mentions that the biggest question people asked Peter during a trip to Australia last year was the impact of self-driving cars on professions like truck drivers. She asks Peter to talk about the fear that algorithms and machine learning are replacing jobs. [01:03:19] Ken mentions that earlier in this decade Peter spoke at the Singularity Summit where he remarked that he was not a believer in what some refer to as “the singularity.” He asks Peter to explain what is generally meant by that term, and also to talk about his views on it. [01:07:44] Dawn comments on the coming “post app era” where a new type of human, computer, and smart-phone technology will replace the need for apps. She asks if this is something that Google is working on. [01:10:25] Dawn mentions that Peter is widely quoted as saying that he has the best job in the world, and asks what it is that he does. [01:12:10] Dawn asks Peter to share some advice for listeners who are still in school and are thinking about going to work for Google someday. [01:12:55] Ken mentions that Peter and his wife enjoy cycling and ends the interview by asking Peter if he has picked up any other new hobbies over the years. Peter’s Google AI page Peter’s Wikipedia page Peter’s web page Peter’s CV Peter’s Google Scholar page Peter’s Amazon page Peter’s Ted Talk Lecture by Peter: “The Science and Engineering of Online Learning” Lecture by Ken: “On Computational Wings: The Prospects & Putative Perils of AI” Learn more about IHMC STEM-Talk homepage  

Episode 71: Elizabeth Nance talks about using nanotechnology to understand and treat brain diseases SEO: Elizabeth Nance, Nance Lab, University of Washington, nanotechnology, autism, traumatic brain injury, epilepsy, nanoparticles, blood-brain barrier,diffusion,dendrimer-NAC conjugates,Einstein’s brain, chemical engineering,Ken Ford,Dawn Kernagis,IHMC Our guest today has been described by Forbes magazine as one of the “most disruptive, game-changing and innovating young personalities in science.” Dr. Elizabeth Nance is known for her passionate search to find ways to more efficiently connect resources and information across multiple scientific and engineering disciplines. Her research focuses on using nanotechnology to understand the movement of molecules in the brain. She is particularly focused on better ways to treat brain diseases like autism, stroke, traumatic brain injury and epilepsy. Elizabeth is the Clare Boothe Luce Assistant Professor of Chemical Engineering at the University of Washington. She also has an adjunct appointment in the school’s radiology department. Elizabeth and her lab, the Nance Lab, recently was awarded a $1.8-million-dollar grant from the National Institutes of Health to develop quantitative, high resolution imaging and analysis platforms to understand nanoparticle behavior, with a specific focus on the brain. In today’s episode, we discuss: The pushback Elizabeth received in college when she tried to apply chemical engineering to neurological diseases. [00:11:33] How Elizabeth developed the first nanoparticles that could penetrate deep within the brain. [00:13:52] The many potential applications of nanoparticle technology in the treatment of neurological disorders, diseases and injuries. [00:17:10] The structure, and unique functions of the blood-brain barrier. [00:28:11] The dendrimer-NAC conjugates, and how they increase intracellular glutathione to reduce injury in the inflamed brain. [00:35:01] How “disease directing engineering” has the potential to allow for the leveraging of common hallmarks of neurological disease to better deliver therapies. [00:40:19] How change in brain metabolism affects targeted therapeutic deliveries to a specific region of the brain. [00:52:14] Show notes: [00:03:31] Elizabeth talks about growing up in North Carolina and how her family goes back nine generations to the original homesteaders of Charlotte. [00:04:06] Dawn mentions that Elizabeth liked to spend a lot of time outdoors as a child and asks her if it is true that she was especially good at climbing trees. [00:05:12] Dawn asks Elizabeth about her hectic schedule in high school, which, in addition to her studies, included soccer, track and volleyball. [00:06:03] Ken asks Elizabeth when she became interested in science. [00:08:22] Dawn mentions how in North Carolina a person has to decide early on if they are a Chapel Hill fan or a North Carolina State fan. Dawn asks if this culture contributed to Elizabeth going to NC State. [00:09:28] Dawn asks Elizabeth about her decision to major in chemical engineering. [00:11:33] Dawn asks Elizabeth to discuss the pushback she received in college when she tried to apply chemical engineering to neurological diseases. [00:13:52] Ken mentions that Elizabeth developed the first nanoparticles that could penetrate deep within the brain. This was a major reason why Forbes named her one of its “30 Under 30 Disruptive Influencers in Science” back in 2015. He asks if she could talk about the work she did in developing that platform and how it changed the way we might think about delivering drugs in the brain. [00:17:10]Ken mentions that there are many potential applications of nanoparticle technology in the treatment of neurological disorders, diseases and injuries. He asks Elizabeth to describe the structure of a nanoparticle in general, and how it can accomplish targeted delivery of a therapeutic. [00:21:47] Ken comments on how after publishing her nanoparticle paper in “Science Translational Medicine” in 2012, one publication commented that they were worried about potential nefarious applications of such technology. [00:25:23] Dawn asks why research and development for drugs used to treat people with injured or diseased brains take about 35% longer to develop than drugs for any other type of disease. [00:28:11] Dawn asks Elizabeth to give some background on the structure, and unique functions of the blood-brain barrier. [00:29:57] Ken discusses how a lot of Elizabeth’s work involves the use of nanotechnology and its potential applications in both understanding and treating the injured brain. He asks about the use of nanoparticles as probes, and how that helps us better understand the human brain microenvironment. [00:32:11] Dawn comments on how much of Elizabeth’s post-doctoral work focused on the use of dendrimer-based nanoparticles in multiple different settings as a model for how to approach neurological disease treatment. Dawn asks Elizabeth how that has informed her current research. [00:35:01] Dawn brings up how Elizabeth has published multiple papers on the dendrimer-NAC conjugates, and how it increases intracellular glutathione to reduce injury in the inflamed brain. Dawn goes on to say that some people have begun to take NAC to increase glutathione in the brain after a concussion or TBI. She asks Elizabeth to talk about the potential problems with giving NAC in the setting of excitotoxic brain injury, and why the use of a nanoparticle might be a potential solution to this problem. [00:37:30] Ken comments on how Elizabeth is known to be fascinated by diffusion, to the point where she has said that it has kept her up at night. He asks why understanding diffusion is so critical to overcoming the barriers to investigating and treating the injured brain. [00:40:19] Dawn mentions that a number of things that happen after brain injury can dramatically alter our ability to deliver a therapy. She points out that Elizabeth has coined the term “disease directing engineering” to describe an approach that has the potential to allow for leveraging of common hallmarks of neurological disease to better deliver therapies. She asks how that thought process informs the research in Elizabeth’s lab. [00:43:37] Ken brings up one of Elizabeth’s review papers, where she summarized how nanoparticle properties affect movement within the brain, and from that she developed a formula with the highest likelihood of success. He asks what that formula is. [00:46:16] Dawn comments on Elizabeth being very vocal about the drug delivery field’s movement toward increasingly complex delivery vehicles despite the limited translation of these approaches in the clinic. She goes on to ask why there is this gap. [00:48:34] Dawn mentions that Elizabeth and her lab were recently awarded a $1.8 million grant from the NIH, and how she will be using the grant to develop quantitative high-resolution imaging and analysis platforms to understand nanoparticle behavior and compartmentalization on brain tissues. [00:49:45] Dawn asks if Elizabeth could explain the idea behind her current work, which focuses on integrating biological data from the molecular level all the way up to animal behavior. [00:52:14] Ken comments on how we know that in certain types of brain injury or disease, that metabolism and inflammation are significant components of the underlying pathophysiology. He asks if a change in brain metabolism affects targeted therapeutic delivery to a specific region of the brain. [00:54:47] Ken asks if the leakiness of the blood brain barrier that occurs in certain forms of neurological injury and disease can be utilized in a targeted way to deliver a drug in the brain. [00:56:54] Ken asks what Elizabeth sees as the most exciting up and coming areas of nanoparticle therapeutics research and development. [00:58:20] Dawn asks Elizabeth about her decision to join the University of Washington. [00:59:40] Dawn asks if Elizabeth’s adjunct position in the department of radiology helps her interact with clinicians or medical researchers who might wonder why a ChemE is working on the brain. [01:00:49] Dawn asks if Elizabeth can expand on her idea that while interdisciplinary research is frequently talked about, that people are usually just giving it lip service. [01:02:37] Dawn mentions that Elizabeth’s father was a minister, and her mother a nurse, and that one thing they instilled in her early on was that every person and conversation has value; and that a person has to be constantly willing to go outside their comfort zone in order to grow. She asks how these lessons shaped the philosophy behind Elizabeth’s lab. [01:03:56] Dawn brings up a TED Talk that Elizabeth did where she stressed that we have made significant advancements in treating disease because of better prevention, better surgical intervention, and better diagnosis. But despite all this, we are still struggling to understand the majority of complex diseases, and that it is possible that we already have the tools we need to solve those problems but our approach to using them might be the issue, and that we might have the solutions already but we are just asking the wrong questions. [01:05:06] Dawn mentions Elizabeth’s shift from ChemE to neuroscience and pediatrics after her Ph.D. led people to ask her on a regular basis, “What are you? What is your specialty?” Dawn asks if that is why Elizabeth often refers to herself as a glorified match maker? [01:06:41] Dawn refers back to something Elizabeth said in her TED Talk about the idea of “specializing in not specializing”, and asks her to expand on that concept. [01:08:28] Dawn asks Elizabeth about recently being named the European Union’s NanoMed Innovative Training Network’s Inspiring Young Investigator of 2018. [01:10:08] Ken mentions that Elizabeth was recently on a podcast where she shared a remarkable story about how pathologist Thomas Harvey kept parts of Einstein’s brain after performing the autopsy on him in 1955. Some of the sections of the brain were recovered and analyzed decades later, showing that the structure and composition of his brain might have been slightly different from what we might normally expect to see. Ken asks if Elizabeth could discuss what those differences were and how this highlights the importance of probing. [01:12:40] Dawn mentions that episodes 47 and 48 of STEM-Talk featured a two-part interview with Tommy Wood, a UK trained physician and Ph.D. who now also works at the University of Washington. When Dawn and Ken asked Tommy what brought him over to the U.S., he said “a girl.” Dawn asks Elizabeth if she knows something about that. [01:13:31] Even though Forbes named Elizabeth one of its “30 under 30 in Science” in 2015, Dawn mentions that she understands Elizabeth was terrible at chemistry in high school. Dawn wraps up the interview by asking Elizabeth if that’s true. Links: Elizabeth’s University of Washington faculty page Nance Lab website Elizabeth’s TEDx Talk Facebook page Instagram Elizabeth’s podcast interview where she talks about Einstein’s brain A Dense Poly(Ethylene Glycol) Coating Improves Penetration of Large Polymeric Nanoparticles Within Brain Tissue Systems-level thinking for nanoparticle-mediated therapeutic delivery to neurological diseases Tommy Wood STEM-Talk interview, episode 47 Tommy Wood STEM-Talk interview, episode 48 Learn more about IHMC Ken Ford Facebook page Dawn Kernagis Facebook page  

Peter Attia, who was our very first guest on STEM-Talk, describes David Sabatini’s discovery of mTOR as one of his two favorite science stories. Today, Dr. David Sabatini joins us and gives us a first-hand account of how his research into rapamycin in 1994 as a graduate student led him to the discovery of mTOR, which we now know is a critical regulator of cellular growth. Our interview with David delves into his continuing research into mTOR, which has led to promising opportunities for the development of new treatments for debilitating diseases such as cancer, diabetes and neurological disorders. He also discusses mTOR’s role in healthspan and lifespan. David is a molecular cell biologist who, according to Reuters News Service, is on the short list for a Nobel Prize. David is on the faculty at MIT and heads up the Sabatini Lab at the Whitehead Institute. In today’s episode, we discuss: • Rapamycin, a macrolide antibiotic discovered in the soil of Easter Island • David’s discovery of mTOR while a grad student at Johns Hopkins • mTOR’s role as one of the major growth pathways in the body • mTOR’s role as a nutrient sensor • How mTOR inhibiton has become one of the hottest topics in longevity research • mTOR’s role in diseases, especially its connection to cancer • The role of RAG GTPases as key mTOR mediators • Protein intake and downstream mTOR activation • Research into ketogenic diets effect on longevity and healthspan • Whether David would take rapamycin as a means to enhance his longevity • And much, much more Show notes: [00:03:32] David talks about growing up in New York and having parents who immigrated to the United States from Argentina. [00:04:00] Dawn asks what David was like as a kid. [00:04:59] Dawn asks David about his decision to attend Brown University. [00:05:56] David talks about his decision to become a scientist and the time he spent in the lab of Al Dahlberg [00:06:53] Ken mentions that after his time at Brown, David headed off for Johns Hopkins to work in Sol Snyder’s lab, a professor known particularly for the work he and his colleagues did on the opioid receptor. Ken asks what drew David to Sol’s lab. [00:08:25] David talks about how as graduate student at Johns Hopkins in the M.D./Ph.D. program, he began trying to understand the molecular mechanism of rapamycin, a macrolide antibiotic discovered in the soil of Easter Island. Rapamycin was known as a potent antifungal, immunosuppressive with anti-tumorigenic properties. That research led David to the major discovery in 1994 of the protein to which rapamycin binds, now referred to as the mechanistic target of rapamycin, or mTOR. [00:11:46] Dawn asks David to give a high-level definition and overview of what mTOR does. [00:13:44] Dawn asks why the “m” in mTOR went from standing for “mammalian” to “mechanistic.” [00:14:11] Ken mentions that we now know mTOR is one of the major growth pathways in the body that is responsible for growth in both a positive sense and a pathologic sense. He goes on to mention that mTOR acts as a major switch between catabolism and anabolism, and asks David to explain why both of these processes are essential for survival. [00:16:10] Dawn asks how the two different mTOR protein complexes, mTORC1 and mTORC2, differ with regards to their activation and downstream function. [00:17:40] Dawn asks David about his decision to join the faculty atMIT and embark on a research-focused career there, starting his own lab at the Whitehead Institute rather than following the clinical path arising from his M.D. [00:20:50] Ken asks about how nutrients and other inputs are sensed and integrated by the mTOR complexes, given how one of the most fascinating aspects about mTORC1 is its role as a nutrient sensor. [00:23:46] Ken asks why both nutrients and growth factors are required to activate mTORC1. [00:25:54] Dawn mentions her interest in the connection of mTOR to aging, mentioning that mTOR inhibition through rapamycin or its analogues is currently one of the hottest topics in longevity research. She asks why mTOR inhibition  appears to be life-extending? [00:30:38] Ken asks what the risks are of excess catabolism, when inhibiting mTOR pharmacologically, in terms of both health and longevity. [00:32:09] Dawn asks if there is data in humans suggesting that suppressing mTOR will extend longevity and healthspan, either pharmacologically, genetically or through diet and fasting. [00:34:23] Dawn asks where mTOR is made, both in terms of the individual cell, as well as specific tissues in the body. [00:35:02] Ken asks if there is a significant difference between the mTOR signaling in organs like the liver, skeletal muscle, and the brain. [00:37:07] Ken asks if tissue specific inhibition of mTOR is possible. [00:38:29] Dawnmentions how it is becoming clear that mTOR plays a role in a number of diseases, most notably is its connection to cancer. She goes on to say that in 2008, David’s team published a highly-cited paper in Science that described the role of Rag GTPases, key mTOR mediators, that sense the amino acid input of a cell. She asks David to discuss this discovery and about the importance of these enzymes in disease processes like cancer? [00:42:27] Ken mentions that protein intake and downstream mTOR activation is often said to be associated with dysregulated cell growth (i.e. cancer). He goes on to ask if there is there sufficient evidence to suggest that high levels of protein or amino acid intake are necessary or sufficient to produce clinically-meaningful cancers? [00:43:59] Dawn comments on the epidemic of type-2 diabetes in the United States, going on to say that the mTOR pathway is a known suppressor of the insulin-signaling pathway. She asks if mTOR modulators have the potential to make an impact in the diabetes world? [00:45:28] Ken asks if the potential negative effects of protein intake on mTOR activation and longevity might be mitigated in the presence of lower-blood glucose or insulin signaling, given the overlap between the insulin and IGF-1 signaling pathways. [00:46:31] Dawn opens the question by mentioning that late last year, the journal Cell Metabolism published two excellent papers related to ketogenic diets and the extension of healthspan and lifespan. She goes on to mention that the paper from Keith Baar’s group at UC Davis titled “A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice” was of particular interest to several people at IHMC. The findings showed that in mouse models, researchers have seen extended longevity, cognitive protection, cancer reduction, improved strength and coordination, and immune rejuvenation.  The paper from the team at UC Davis, showed a 13% increase in median life span for the mice on a high fat vs high carb diet. Ken jumps in and mentions that from his perspective the most important aspect is that those mice retained their quality of health well into later life. He mentions that it was particularly interesting that they found the ketogenic diet increasedprotein acetylation levels and regulated mTORC1signaling in a tissue-dependent manner. Specifically, the ketogenic diet increasedmTOR signaling in skeletal muscle and inhibited mTORC1 signaling in the liver. [00:48:59] Ken mentions that an interesting paper from a year or two ago showed that ketones, particularly BHB, greatly increased IGF-1 sensitivity in the muscle. [00:50:59] Dawn asks what the role of mTOR is in neurodegenerative diseases such as Alzheimer’s or Parkinson’s disease. [00:53:02] Dawn mentions that mTORC1 responds to intracellular and environmental stresses that are incompatible with growth, including hypoxia. She asks about the effect of hypoxia on mTORC1. [00:53:51] Dawn mentions that the amino acid, methionine, is widely appreciated to have interesting effects on animal physiology, and that diets low in methionine increase longevity and overall health. She goes on to mention a paper David and a group of his colleagues published in “Science” that described a potential molecular link between the effects of methionine restriction and mTOR1. She asks David to give a summary of that paper and his findings. [00:55:27] Ken mentions that several human pathologies are linked to mTOR hyperactivation such as TSC and epilepsy due to gene deletions.  He goes on to ask about the consequences of gene deletion-induced mTOR hypoactivation and if it would it confer a longevity benefit. [00:57:02] Dawn comments on how a few years ago, David joined Peter Attia, our very first guests on STEM-Talk, and a few other friends to take a trip to Easter Island to explore the place where rapamycin was discovered. She asks if David could talk briefly about the story of the initial discovery and isolation of rapamycin on Easter Island, and how, at one point, it was only in Suren Sehgal’s hands and almost lost. [00:59:17] Dawn mentions how David has previously written about how caloric restriction might produce the best balance of mTORC1 inhibition and overall organismal health, asking David to expand on that idea since caloric restriction does not consistently produce life extension in animal models. [01:01:14] Dawn asks if rather than restricting nutrients in mass with caloric restriction, might it be possible to manipulate individual nutrients to extend human life. [01:02:11] Ken mentions that in mammalian cells, inhibition of mTOR results in reduced cell size as a result of reduced protein synthesis. He goes on to ask what the downstream effects are of this, and if it results in a specific phenotype when mammals are exposed to mTOR inhibitors. [01:03:40] Following up, Dawn comments that one might speculate that chronic inhibition of mTOR in humans would likely degrade a patient’s health and cause fragility due to immunosuppression and loss of muscle. She asks if intermittent use of low-dose rapamycin would help avoid these effects and some of the widely observed side effects such as mouth sores. [01:05:11] Ken asks if David would hypothesize about intermittent use of low-dose rapamycin and its potential to activate autophagy in a meaningful way. [01:06:04] Dawn mentions a story about David on the Whitehead Institute website that makes the point that rapamycin appears to have all the makings of a magic bullet for treating diseases involving the mTOR pathway. David, however, was quoted as saying “we’re not there yet”. [01:07:08] Ken asks if we know how long mTOR inhibition takes with rapamycin before mTORC2 is inhibited. [01:08:59] Ken mentions that one hears ofphysicians prescribing rapamycin off label for older patients. He goes on to say that there aren’t sufficient studies to justify this behavior, asking David’s for his thoughts on this. [01:10:13] Ken comments on how the captive mouse studies, where the subjects are fed a bad diet, is not too far removed from human life in cities in many ways. [01:11:06] Dawn asks David what evidence would have to be there to get him to consider taking rapamycin as a means for enhancing his own longevity. [01:12:31] Dawn closes the interview by mentioning that Davidwrote a piece for the Proceedings of the National Academy of Sciences Journal titled, “Twenty-Five Years of mTOR.” Toward the end of that article David wrote that his friends in the field laugh at him whenever he says he’s done with mTOR, that there’s nothing left to discover. Dawn then quotes what David had to say about this: “Whenever I feel like calling it quits, the laboratory conveniently makes a great discovery that piques our interest in a new facet of the pathway.” And while, mTOR may not regulate everything, he went on to say, there are enough mysteries in how it senses everything to keep him and his lab occupied for the foreseeable future. [01:13:07] Dawn closes the interview by asking David to describe some of these mysteries he and his colleagues are exploring. Sabatini links: David M. Sabatini MIT profile page Sabatini Lab website David M. Sabatini Wikipedia page Sabatini Lab publications page Peter Attia interview with David M. Sabatini Twenty-Five Years of mTOR RAFT1: A mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion Amino Acids and mTORC1 Growing Roles for the mTOR pathway Rapalogs and mTOR inhibitors as anti-aging therapeutics mTOR is a key modulator of ageing and age-related disease Regulation of mTORC1 by amino acids mTOR Signaling in Growth Control and Disease The TOR pathway interacts with the insulin signaling pathway to regulate C. elegans larval development, metabolism and life span Tim Ferris podcast about trip to Easter Island with David M. Sabatini and friends