Mind & Matter

About the guest: Eugene Morin, PhD is a Professor of Anthropology at the University of Trent who studies Paleolithic humans and animals.Episode summary: Nick and Dr. Morin discuss: evolution of Paleolithic humans; Neanderthal diet & cultural capacity; key human adaptations related to endurance and stamina; hunter gatherer hunting strategies; evolution of human digestion; and more.*This content is never meant to serve as medical advice.* Support M&M if you find value in this content.* Full audio only version: [Apple Podcasts] [Spotify] [Elsewhere]* Full video version: [YouTube] [Odysee]* Episode transcript below.Full AI-generated transcript below. Beware of typos & mistranslations!Eugene Morin 2:27 Well, I'm a Paleolithic specialist. And I study animal bones, mostly in Europe, more specifically in France and Montenegro. And you know, I started working about 20 years ago. I'm a specialist of Neanderthals and early modern humans. And I focus my I would say most of my research focuses on diet subsistence foraging. And I do a bit of more and more I would say over over the years I'm doing more and more ethnography and that no history. So the study of a non western societies, and I tried to use that as kind of framework to help me interpret the past.Nick Jikomes 3:14 Is there a particular period in time that you focus on?Eugene Morin 3:17 Yeah, so when I send you out to doors and early modern humans, so I study mostly people who lived about 200 to 50,000 years ago, that's basically the range I work on. But I've worked on stuff that is like, almost 600,000 years old. AndNick Jikomes 3:36 would this be the Paleolithic period? Yeah. SoEugene Morin 3:39 that would encompass the lower middle, and Upper Paleolithic as well. Sometimes I work on on later stuff. So but mostly it's it's the Palaeolithic, I would say the later part of the pelvis. AndNick Jikomes 3:52 can you can you just talk about like, what is the Paleolithic era? When did it start? When did and and what defines it? Are there particular archaeological discoveries or events in history that that start? Yeah, yeah. SoEugene Morin 4:05 the public starts as soon as we have them any cultural objects. And so objects made by humans with the goal of assisting them in their activities. So in Africa, it starts about 3.3 million years ago. And we usually take the arm emergence of agriculture as the end of the time period. So it's occurred about 12,000 years ago, in the Near East. I see. So basically, 3.3 million years ago to 12,000 years ago, that's the prolific.Nick Jikomes 4:39 I see. And over that period of time, really just in very general terms, where were humans coming and going. So at the beginning of the Paleolithic were were humans was our lineage of humans. And by the end, where were we across the globe? Yeah,Eugene Morin 4:53 so the prolific it's a world of hunter gatherers, okay, so there's no agriculture and It starts in Africa. And we have hints that there there are some expansion of dominance out of Africa, starting probably around 2.5 million years ago. So they start to colonize the, you know, eastern part of, sorry, the southern part of Europe. Well, it mostly southeast, sorry, Southeast Europe. And then they move into the tropics of Asia. And so we find them, you know, probably around 2 million years ago, 2.5 million years ago, in southern Southeast Asia. And then the two continents, continents are populated later. So Australia would be probably occupied around 45 to 60,000 years ago. And then we have occupation of the Americas. About 25 to 30,000 years ago,Nick Jikomes 5:58 the first species of hominids that were leaving Africa, what what subspecies would that be was that Homo erectus? Was it some other species? Well, that'sEugene Morin 6:09 that's a good question. People are debating this. So some, you know, some people have argued there possibly later, you know, the very late Pleistocene, sorry, very late Australopithecines. Other people think it's only early almost that we're moving out. So that's still debated. I think on the safe side would say these are early Elmo populations.Nick Jikomes 6:32 When we think about the evolution of the genus Homo, that would include ourselves that would include Neanderthals and other things. What, what are some of the key phenotypic features of this, of this genus that distinguish it from other mammals? In particular, I'm hoping you can start out by talking about like physical adaptations, muscular skeletal adaptations, aspects of the body that relate to how we move throughout the world. What are some of the key adaptations of homo?Eugene Morin 7:02 Well, what we see in early amo, is there, you know, we see first they're getting taller relative to Australopithecines. So I'll strip it, the scenes are basically the height of mother and chimpanzees. And so with early on Mo, we see people are standing up, and now are close to, you know, our height. We see in their body that, especially with OMO rectus, the postcrani

About the guest: Monique Smith, PhD is an assistant professor of neurobiology at the University of California-San Diego, where her lab studies the neuroscience of social behavior, pain, and emotion.Episode summary: Nick and Dr. Smith discuss: the neurobiology of pain perception; social & empathy-like behavior in animals; emotion; brain mechanisms of MDMA; serotonin; and more.*This content is never meant to serve as medical advice.* Support M&M if you find value in this content.* Full audio only version: [Apple Podcasts] [Spotify] [Elsewhere]* Full video version: [YouTube] [Odysee]* Episode transcript below.Full AI-generated transcript below. Beware of typos & mistranslations!Monique Smith 2:28 Sure, yeah. My name is Monique Smith. I'm an assistant professor of neurobiology and Neurosciences at the University of California, San Diego. And my lab is very interested in looking at how social behavior impacts pain, emotions, and basically internal state. So we do a lot of work to understand how these things intersect, for example, how does having social partners around you impact your experience of pain after injury? Or another example would be by being around somebody in pain? How do we experience empathy? And how does the brain encode that? But when I say we, we actually use mice as models? And yeah, and yeah, so that's pretty much it. And we're working on some human collaborations. But we primarily use mice to model things like emotions, which some people think is a little wild or out there. But I would argue that most mammals, including mice, and other rodents experience emotional states and are affected by social partners and things like that. So yeah.Nick Jikomes 3:43 What, you know, in your mind, like what, what is a good working definition of emotion? And how do you approach that in an animal that can't speak to you?Monique Smith 3:54 Yeah, so interestingly, we depend as humans upon language to talk about our emotions talk about things like pain, and obviously, animals can't do that. But when you think about our behavioral output, in distressful situations, or painful situations, or situations in which we're experiencing some emotion, the behavior that you can see, that we engage in might be very similar in our roadmap. So in terms of defining something like emotion, there's, you can think of it as an umbrella term that involves sort of arousal on the y axis, if you were to put this on the graph, and then negative to positive effect. And so emotions kind of lie on this graph, or you can think about it circularly in that we can have a high arousal, highly negative feeling, or emotion. Something like rage, let's say, or we can have a low arousal was all really negative feeling. And that would be something like feeling depressed, or, like lethargic because your emotions are bad. And so that's how I like to think about emotions is this sort of intersection between arousal and negative or positive effect. Though with human emotion, we do talk about it as lasting a little bit longer than sort of a really brief state. But I would argue that the emotional state is quite short. And that feelings are what lasts longer. But you can have really rapid changes in emotions, even as a human and I argue we can look at that in animals by measuring their behavior. Does that make sense? Yeah,Nick Jikomes 5:42 so So basically, animals will display characteristic behaviors in certain emotional states or when they're exposed to stimuli that we know elicit emotional states and us, they exhibit behaviors that are akin to the ones that that we display. And what you're saying is, you can think of emotion as having two components. One is this arousal component. So like, when you prick your finger, with a pin, it hurts you, you become aroused, right? You you get like a jolt of energy, you know, your nervous system is excited. But it's also painful. There's a negative aspect to it. So there's these two components, arousal and effect or valence?Monique Smith 6:22 Yeah, yeah. Yeah, exactly. So positive or negative and highly aroused, versus less aroused. And I think if you start to break down emotion into those component parts, then you can see it in terms of behavioral output. Exactly. in lots of different animals. Yeah, I'll say really quick, like, I don't think anyone has an any question that their dog experiences some form of emotion. So I think it's kind of interesting that we think, you know, a dog is that much different than a mouse, which they're different. They're different species, for sure. But yeah, anyways, go on.Nick Jikomes 6:58 So when you study emotion in mice, if you study something like pain, how do you how do you study that? How do you measure it? How do you quantify it?Monique Smith 7:08 Yeah, good question. So I'll start with the human, which I'm sure everyone knows, we asked, how much pain are you in a scale of one to 10 one being the least, you're not in any pain at all, and 10 being the most painful experience

About the guest: Dominic D'Agostino, PhD is a researcher and professor at the University of South Florida, where his lab studies metabolism, human biology, and related subjects.Episode summary: Nick and Dr. D'Agostino discuss: ketosis and the ketogenic diet; effects of ketosis on diabetes, insulin resistance & metabolic health; effects on brain & mental health; relationship with exercise performance; cholesterol, LDL, triglycerides & other biomarkers; cancer; and more.*This content is never meant to serve as medical advice.* Support M&M if you find value in this content.* Full audio only version: [Apple Podcasts] [Spotify] [Elsewhere]* Full video version: [YouTube] [Odysee]* Episode transcript below.Full AI-generated transcript below. Beware of typos & mistranslations!Dominic D'Agostino 2:24 Sure, I am a professor at University of South Florida Morsani College of Medicine. I did my undergraduate in nutrition science and biology. And then I studied neuroscience and physiology with a focus on the neural control of autonomic regulation for my PhD, specifically in the context of the hypoxic response or response hypoxia. And then, as a postdoctoral fellow, I studied extreme environments. And then in my I have a more general kind of education background as a professor, I teach neuropharmacology. I teach nutrition, I teach physiology. And I teach medical students, PhD students, masters students and honors undergrad students. And I do about 50% teaching 50% research. And yeah, run our research lab and do teaching.Nick Jikomes 3:23 What uh, what do you work on in the lab these days? What's the focus? Yeah,Dominic D'Agostino 3:28 we have a lot of different projects. I should mention also cancer research we do. The last conference I came from was on an inborn error of metabolism called glycogen storage disease. Type two, which is also good Pompe Disease. There's a number of these inborn errors of metabolism, that these disease processes are highly receptive to ketogenic interventions that change metabolic physiology, brain energy metabolism. We've studied glucose transporter type one Deficiency Syndrome, Kabuki syndrome, which is a genetic disorder disorder, where the ketone bodies app act as epigenetic regulators on gene expression. I've studied Pompe Disease Angelman syndrome, I guess, I guess what you could say what pays the what has paid the bills in the in the lab and allowed me to expand into different applications is navy funding to develop ketogenic strategies to enhance warfighter resilience in extreme environments. So that would be like high oxygen environment associated in a high hyperbaric pressure environments. So we've I've worked in the capacity of looking at nanoscopic changes with atomic force microscopes to laser confocal to my study Use rat studies, collaborative pig studies, human studies where I've been a subject living in a hyperbaric environment, underwater for 10 days where I'm the subject. And I do research on astronauts because they train in these extreme environments in isolated extreme environments for their preparation for the space station. So that would be NASA's extreme environment. Mission operations are Nemo 22, and my wife was on Nemo 23. So we've studied everything from the mitochondria to like, the whole human and everything in between, or extreme environments,Nick Jikomes 5:35 when you're in that hyperbaric environment. What what's it like? What happens? What are some of the the adaptations of the human body when when someone goes into those conditions?Dominic D'Agostino 5:44 Yeah, you know, it's, you know, the human body is incredibly adaptable. I teach nutrition. So it's amazing that like, we can adapt to so many different nutritional things to eating just underprint plants to 100% meat. And it is remarkable how adaptive we are. Yeah, I was gonna say at least in the short term, but in the relatively long term, to changes in the composition of gases and pressure. So I was in the Aquarius habitat, which is off of the keys and Isla Murata about five, six miles off. And it's a it's it's a submerged habitat, that's down to about almost three atmospheres of pressure. So unlike a submarine, which stays at one atmosphere pressure, the submerge habitat for training is about three atmospheres of pressure. And then you can go outside of that, and do work. And that's that's called like EBA, or extra vehicular activity. If you're on the space station, and you go outside to Space Station to work on it, that's called an eta. So you get like, suited up to do EBA is to do different work things. So we measured, some of that's published them, it's not. But we have, for example, we were like the aura ring. So we look at sleep. Look at HRV, we were the polar v 800. So we get a little bit higher HRV. We look at the microbiome, how the microbiome changes and extreme like skin microbiome, the microbiome of the underwater habitat, which is kind of interesting. We look at blood, we do blood samples of li

About the guest: Robert Lufkin, MD is a radiologist and professor at UCLA. His new book is called, "Lies I Taught in Medical School."Episode summary: Nick and Dr. Lufkin talk about: the history of medicine in the United States; diet & lifestyle vs. pharmaceuticals in acute vs. chronic disease; diabetes, metabolic syndrome & insulin resistance; health institutions like the American Diabetes Association & American Heart Association, including their financial influences; carbohydrates, fats, dietary cholesterol, ketosis, and related topics in metabolism; bloodwork & choosing the right doctor; and more.*This content is never meant to serve as medical advice.* Support M&M if you find value in this content.* Full audio only version: [Apple Podcasts] [Spotify] [Elsewhere]* Full video version: [YouTube] [Odysee]* Episode transcript below.Full AI-generated transcript below. Beware of typos & mistranslations!Robert Lufkin 2:25 Yeah, well I sincerely spent my whole My name is Robert Lufkin, I've spent my whole career in academic medicine as a professor at a couple large medical schools here in Southern California. In my being a professor I, I was fortunate to be able to not only practice medicine, but also do research and, and also teach so it's it's a great, great thing from that point of view from and and I was basically represent the medical establishment. I'm not a conspiracy theorist or anything I'm, I'm about as mainstream as they get. I mean, as example. My publications I have my my specialty is medical imaging, although, in the last 10 years, for reasons we'll probably get to, I've transitioned into metabolic health and longevity, largely out of self interest. But, but my, my academic background is in medical imaging and and like I said, doing research I, I, my laboratory took millions of dollars from or was was granted millions of dollars from the federal government from drug companies from equipment manufacturers, we did a lot of research over 200 peer reviewed publications. Doing you know, all the things I've served as president of a couple International Medical Society, so I'm really you know, I'm really mainstream medicine and, and, for the record, I believe that Western medicine is actually it unequaled in its ability to handle certain things. I'm not out to throw out Western medicine. I think, for example, if I have a you know, any number of infectious diseases, I'm gonna go to Western medicine and it's been very effective in the 20th century for eliminating public health, diseases and really improving our lifespan. Similarly, if I step out in the street, I get hit by a bus. I while lifestyle and nutrition may help me recover from that event, I will only survive that event if I have access to the latest cutting edge Western medicine, which will include blood transfusions, bone settings and you know, surgery To reconnect my, you know, whatever soft tissue damage I have. So Western medicine is really in my opinion unequaled and in its ability to do those things. And the problem is when we apply those Western medicine approaches to certain diseases that we'll be talking about later. But anyway, my background, that's my background. I still am a professor. Although my focus, like I said, is now metabolic health and, and longevity. AndNick Jikomes 5:34 one thing that was interesting, so so your new book that's coming out, you start out with a description of of your mother. So can you kind of give give that story to people? Who is your mother? And what was she doing in terms of diet nutrition when you were growing up?Robert Lufkin 5:51 Yeah, well, I mean, obviously, all our mothers are formatives in our formative in our lives, and our dads too. But it just so happened that my mom was a dietitian, and she was she worked in hospitals, all her life into her 80s Really, and and so what that meant to me is growing up, we were exposed to the latest, the best health care recommendations as far as nutrition, which, you know, for better or worse, at the time meant that we had a essentially a low fat high carbohydrate diet, we avoided things like butter, because of saturated fat, we thought it was harmful. And we substituted what we thought was healthy, which was margarine, which is full of trans fats and seed oils. We, you know, we avoided fat on meat, we would trim off the fat in the corner of our, our meat, and we follow the food pyramid, religiously. So the idea that that food influence our health was definitely imprinted on me. It just so happened that the wrong the wrong choices were I was subjected to many of the wrong foods growing up as many people still are. Because there's there's a lot of a lot of controversy and difference of opinions on what good diet represents today.Nick Jikomes 7:22 Yeah, I mean, you know, people are really passionate about diet they get, there's almost a kind of religious zeal that many people have with their diet, they get really attached to certain diets. You know, you've got vegans,

About the guest: Stephen Sideroff, PhD is a clinical psychologist and Associate Professor of Psychiatry and Behavioral Sciences at UCLA. His new book is, "The 9 Pillars of Resilience."Episode summary: Nick and Dr. Sideroff discuss: childhood & developmental psychology; clinical & Gestalt psychology; stress & resilience; pharmaceuticals, talk therapy, and plant medicines; emotions & psychopathology; and more.*This content is never meant to serve as medical advice.* Support M&M if you find value in this content.* Full audio only version: [Apple Podcasts] [Spotify] [Elsewhere]* Full video version: [YouTube] [Odysee]* Episode transcript below.Full AI-generated transcript below. Beware of typos & mistranslations!Stephen Sideroff 2:24 It's my pleasure. AndNick Jikomes 2:26 you're you're a clinical psychologist. Right?Stephen Sideroff 2:29 Right. Correct.Nick Jikomes 2:30 So what is what what is your day to day look like? And what is your career look like? At a high level? What's your background? Do you do mostly research? Do you see patients do you do both?Stephen Sideroff 2:40 So I love my career because I see clients, I do consulting with corporations. I do research. I'm a professor at UCLA in psychiatry and rheumatology, I train therapists at UCLA I trained the staff at UCLA. So it's good I got my fingers in a lot of different places.Nick Jikomes 3:10 And in terms of the clinical side of this, the patients you see, or that you've seen throughout your career, is it a certain type of person is an adult as a children is that people have certain cycle pathologies? Is it normal, otherwise normal people.Stephen Sideroff 3:25 So over my career, I've worked with all kinds of people. But in more recent years, I'd say they fall into two categories. One are people who find their way to my door because they're dealing with some overwhelm around stress. There, they have maybe referred by their physician because they have sleep problems or other physical symptoms, or emotional burnout breakdown because of that. Well, the other category are people who feel stuck in their lives, it's like, as hard as they work, they just can't seem to get to the next level. And so I would say those are the two basic categories of people that I see mostly. And then in my, my corporate work, I do work with senior executives and CEOs on how to be a more effective leader.Nick Jikomes 4:28 And do you have like a certain, like, clinical approach or school of thought you belong to like, I remember when I when I took psychology classes when I was younger, you would always learn about you know, the different schools of thought there's you know, inter transpersonal psychology there's cognitive behavioral psychology, there's, you know, psychoanalysis and all the historical schools of thought, is there one that you fit into, or do you think about it even in those terms?Stephen Sideroff 4:54 Well, it's interesting because I started out my career in experimental psychology and phys illogical psychology and I was doing brain research. So I began from a behavioral perspective conditioning perspective, which I found to be very valuable. And then when I moved into clinical I, my, my first training was in Gestalt Therapy, which really resonated with me. And I found it very helpful. But over the years, I really have gotten training in almost every type of approach. Because no one approach has a monopoly on the truth. They each have a piece that I've put into the puzzle of the picture that I use now, which really incorporates from all of those different approaches I, I also apprenticed with a shaman for 15 years, a shaman from South America for 15 years. And so I have that indigenous, naturalistic approach as well. They all have something to offer the ancient, the modern. And really to be most effective, I've found that when I integrate the best of all of those that I have my greatest success.Nick Jikomes 6:21 When we think about, like, where our personalities and our habits come from, so whether or not it's a severe form of psychopathology like OCD, say, or something like that, or it's something more normal and mundane, like just the way that you deal with stress, or some of the little habits and patterns you fall into? How do those things start to get settled into the mind? When we're when we're children? How much of it is natural, natural sort of innate dispositions we have? How much of it is conditioning from our parents in our environment? And how do you start to think about how habits are formed as we then think ahead, how they're broken and modified? Well,Stephen Sideroff 7:05 you're touching on something that's a very important part of the work I do in terms of helping people become more resilient. Because we learn how to operate in the world based on our childhood environment and the lessons of childhood. So we don't go as we're in this very early survival, adaptive learning process. And as a child, it's like, survival learning, right? And so we don't, b

About the guest: Andrew Dillin, PhD is Professor of Molecular & Cell Biology at UC-Berkeley and Howard Hughes Medical Institute investigator. His lab studies mechanisms of aging, mitochondrial biology, and related subjects.Episode summary: Nick and Dr. Dillin discuss: cell biology; mitochondria & the endoplasmic reticulum; aging & autophagy; mitochondrial biology in neurons; diet, exercise, and oxygen effects on mitochondrial health; and more.*This content is never meant to serve as medical advice.* Support M&M if you find value in this content.* Full audio only version: [Apple Podcasts] [Spotify] [Elsewhere]* Full video version: [YouTube] [Odysee]* Episode transcript below.Full AI-generated transcript below. Beware of typos & mistranslations!Andy Dillin 2:25 Thanks for having me. Nick.Nick Jikomes 2:26 Can you give everyone just a brief overview of what you do? And what your lab studies?Andy Dillin 2:32 Yeah. It's, it's a really interesting group of people that I work with. And we're we've sort of stumbled across a really interesting set of findings where we've uncovered that if you have different Seiler stress responses, if you engage them the right way, they can increase lifespan and healthspan and improve a lot of different things. And that was very exciting. But the really cool thing is you only have to engage them in the nervous system. And once they're engaged, they're the nervous system takes over and sort of coordinates this across the rest of the organism. And so for the last 20 years, we've been trying to figure out what that coordination is and what it looks like, and who's doing the coordinating. And, you know, evolutionarily, why would this evolved this way? You know, why doesn't every cell just set up its own stress response? And so on ability to do this? Why does it have a mass for cell types coordinate this?Nick Jikomes 3:33 Yeah, so So you've studied so so the stress response, you know, in principle, you can imagine that each cell is almost like its own little island, it's going to age at its own rate, it's going to respond to whatever's happening right there to that cell. But on the other hand, you could also imagine that, you know, we are organisms with bodies, all of our cells have to be sort of aligned with a common interest in in survival and reproduction. So maybe there are mechanisms that allow full body communication across cells to coordinate stress responses and things like that. Before we get into some of the details there, I want to talk a little bit about some of the basic cell biology just to get people thinking about some of the the organelles and stuff that I think we'll talk about one very important organelle that many people have heard of, and maybe understand, you know, a slice of what these things do is the mitochondria. Can you just talk a little bit about mitochondria, what they are, and what they do, not only in terms of like, what what the average sort of biology student probably knows them for, but you know, the expanded list of important things they do?Andy Dillin 4:40 Yeah, I think that's a great question. So first of all, I have to qualify that when I started my career. Number one, I never thought I'd work in mitochondria. And number two, I never thought I'd be labeled as a neuroscientist. But you know, it's, you just follow where the results send you and we discovered mitochondria in this pathway, and then it works in the nervous system. But to get your quote, you know, mitochondria, I mean, we all, you know, we hate saying this as mitochondrial biologists the powerhouse of the cell, that's what everyone recognizes them for, you know, the major energy producing organelle in your in your cell to produce to produce ATP, ATP, but also have a myriad of other functions. And when we think about that myriad of other functions, we need to actually go back and remember what mitochondria were. So you know, mitochondria were bacteria. And so billions of years ago, you know, one bacteria made another bacterium, and somehow the bacterium that got engulfed, figure it out to give up most of its genome to its hosts, and survive inside the host. And that happened, and it became a very symbiotic relationship. And that's how mitochondria evolved is out of that symbiotic event that happened. So,Nick Jikomes 6:00 so one bacteria ate and other bacteria. And somehow, I imagine, we don't know exactly how this worked. But we know that the what became the mitochondria, that bacteria literally, like gave some of its genes to the host cell, and sort of that was like the deal. That's how alignment was achieved.Andy Dillin 6:19 Yeah, the deal, you know, I think it had to be deals, plural, it had to happen over you know, over time giving up, you know, it didn't all at once give up 99% his genome, it probably did it, you know, over successive generations, but it's fascinating. You know, it's probably the most important biological event that happened on planet Earth, you know, is this ability

About the guest: Eske Willerslev, PhD is an evolutionary biologist and Professor of evolution at both the University of Copenhagen and University of Cambridge.Episode summary: Nick and Dr. Willerslev discuss: human evolution out of Africa; the origins of modern Europeans; hunter gatherers, early farmers, and pastoralists; genetics of human disease risk; evolution of diet & metabolism; evolution of light skin color; and more.*This content is never meant to serve as medical advice.* Support M&M if you find value in this content.* Full audio only version: [Apple Podcasts] [Spotify] [Elsewhere]* Full video version: [YouTube] [Odysee]* Episode transcript below.Full AI-generated transcript below. Beware of typos & mistranslations!Eske Willerslev 2:25 I'm calling in from Lagos just north of Copenhagen, Denmark. So I'm both a professor here at University of Copenhagen and also at the University of Cambridge in Britain. So that they are tomorrow I'll head off to Cambridge.Nick Jikomes 2:40 And are you Danish? Originally?Eske Willerslev 2:43 I'm Danish. Yes, exactly.Nick Jikomes 2:45 Well, by birth, yes. Can you tell everyone a little bit about who you are? And what you do as a scientist? Yeah.Eske Willerslev 2:51 So I'm an evolutionary biologist. And my primary tool is what we call ancient DNA. Right. So it's it's genetic information from the past. And we're both retrieving such information from human teeth from animals, but also, from ecosystem, entire ecosystems by retrieving it directly in a directly from ancient soil. So we we are, you can see, using this tool to address quite diverse questions, everything from you can say, human spread across the world, you know, changes in lifestyle with humans, to the extinction of the last big portrait mega fauna, I mean, the big part of mammals in the end of the last ice age, to you know, how ecosystems are changing. And right now, actually, my focus is to try to take some of these changes from the past adaptive changes, and then see if we can get them into present day crops to make them more resilient towards climate change, for example. So it's, we also look at pathogens, human pathogens, so it's very diverse, you can see what we're doing. But the toolkit is a most parts, this ancient DNANick Jikomes 4:22 in terms of looking at ancient human DNA, one so in one sense, you're looking at things that are very old, you're looking at, you know, humans that were around 1000s 10s of 1000s of years ago, in another sense, you're looking at actually recent human evolution, because it's, it's a much more recent picture of how humans changed just in the last few 1000 years, compared to say, someone who's studying like Neanderthals or humans from millions of years ago. So when you're studying humans, that, that we that are our ancestors 1000s of years ago, 10s of 1000s of years ago. What's special about that time period, and how do you actually How do you actually obtain this DNA? Yeah?Eske Willerslev 5:02 Well, it's a you can see, it's, you know, a lot is happening within the last 10,000 years of you can see human history, human evolution, right. It's, it's the period where we are undergoing the changes in different parts of the world from being on the gathering, which we have been, you know, since we emerged as a species around 600,000 years ago, into new lifestyles. So, so in terms of lifestyle, there's not that much you can say, it seems that is changing until around 10,000 years ago, and then everything changes. And so therefore, it's, it's a very, you know, this more recent, if you can say, the more recent part of, of human history and human evolution is actually very interesting. We are, we are getting a DNA from all kinds of ancient skeletons. So it's really, you can say it's from collections that has, in some cases existed, you know, for more than 100 years in, in various museums, sometimes we also participating in excavations ourselves, I mean, so basically getting the material fresh out of the ground. And there's really two types of materials from humans we are particularly interested in one is teeth, because teeth, has in general, pretty good preservation of DNA. But they also we have learned, they also contain DNA from the blood borne viruses and DNA viruses and bacteria that the humans were carrying at the time of death. SoNick Jikomes 6:46 you can, you can get a picture of not just the human DNA, but the pathogens that they were interacting with.Eske Willerslev 6:51 That's exactly right. And the other piece is what is known as the petrous bone, which is basically fused to the inner side of your skull is part of the year. And that's the most dense bone in the human body. And therefore, it's particularly well preserved the DNA they are part opposite the teeth, you are, you're normally not getting, there's not much of blood flow in the petrol, so you're normally not getting the pathogens. So the beauty about the teeth is if you can get DNA out of the teeth, you're both gett

About the guest: Georgia Ede, MD is a psychiatrist and author of, "Change Your Diet, Change Your Mind: A Powerful Plan to Improve Mood, Overcome Anxiety, And Protect Memory for a Lifetime of Optimal Mental Health."Episode summary: Nick and Dr. Ede discuss: glucose vs. ketones for brain energy; metabolic health & insulin resistance; animal vs. plant-based foods; nutrients, anti-nutrients & plant toxins; ketogenic, carnivore & plant-based diets; carbohydrates & processed foods; treating bipolar disorder, schizophrenia & psychiatric illness with diet; and more.*This content is never meant to serve as medical advice.* Support M&M if you find value in this content.* Full audio only version: [Apple Podcasts] [Spotify] [Elsewhere]* Full video version: [YouTube] [Odysee]* Episode transcript below.Full AI-generated transcript below. Beware of typos & mistranslations!Georgia Ede 2:25 I'm a psychiatrist based in Massachusetts, I've been practicing psychiatry for 25 years. And for the first 10 years of my practice, I practiced conventional psychiatry, medications and psychotherapy, and then gradually incorporated more and more nutrition principles into my practice. And now for many years now, the cornerstone of my work has been metabolic and nutritional psychiatry, centering primarily around ketogenic diets, but other types of dietary strategies as well to help people address the root causes of mental health conditions and help them use less medication sometimes even avoid medications entirely. So that's been, that's been my passion for the for the past 15 years. INick Jikomes 3:13 want to start off by just talking about neurons and and energy and get people thinking about how the brain uses the food that we consume for energy. So in relatively basic terms, how do our neurons How do the cells in our brain actually utilize energy? What are the energy sources they can use? And how do they actually use it?Georgia Ede 3:34 So the brain is a very, I call it an energy hog, you know, it needs lots and lots of energy, because it's, the way that it works is it needs to generate electricity. And so in order to generate electricity, you need a lot of energy. And so the brain is designed to burn ideally, small molecules, and its two favorite molecules to burn are glucose, which comes from blood sugar. Glucose is the sugar that's circulating in our blood simple sugar molecule, and ketones, which are a small fragment of fat. So if you're burning fat, you can generate ketones. If you're burning carbohydrate, you can generate glucose. And so these very small molecules they cross into the brain. And brain cells can use them for energy. And when they do many things with that energy, but one of the most important things they do with that energy is generate electricity. So if the, if the energy supply to the brain isn't reliable and smooth, then you can see all kinds of things go wrong with the brain. The brain can lose its balance in terms of its ability to produce smooth energy supply, and you can see destabilization, you can see mood instability, you can see energy levels that are too high or too low, unpredictable. And you can gradually over time the brain can, cannot can lose even cells and some of the cells can begin to die if they're on If there isn't enough energy available, so energy is really key to the smooth, reliable operation of the brain.Nick Jikomes 5:08 Okay, so the brain uses a lot of energy, in large part to generate electricity. So the neurons can send the electrochemical signals that that they actually send to each other. It sort of makes intuitive sense. There's a lot of electricity going on up there. And so you need a lot of energy to fuel that. There's lots of proteins that facilitate that, that pump the ions and stuff in and out of the cell. And then of course, the chemical messengers themselves, things like neurotransmitters, they they need to be made, they need to be stored, they need to do what they do. How does the diet connect to things like the neurotransmitters that our brands are actually using as messengers? Are they made out of components of the diet? What what is the connection there? SoGeorgia Ede 5:53 everything in the brain comes from the food we eat, there wouldn't be anywhere else for it to come from. And I think sometimes people don't think enough about that, is that, you know, I was trained, obviously, in medical school and in psychiatry residency, to treat so called chemical imbalances with medications to try to try to improve people's brain chemistry, with medications and medications do have an effect on brain chemistry. But one of the things I like to help people appreciate the relationship here is between the food and the brain, because really, the most powerful way to change your brain chemistry is through food, because that's where brain chemicals and every other component of the brain comes from. So, so yes, you're right. So of course, that every piece of the brain comes from food, and jus

About the guest: Ryan Vandrey, PhD is a Professor of Psychiatry & Behavioral Sciences at Johns Hopkins University, where his lab studies the behavioral pharmacology of cannabis (marijuana), nicotine/tobacco, and other substances.Episode summary: Nick and Dr. Vandrey discuss: marijuana; cannabinoids like THC; terpenes like limonene, myrcene, and pinene; the entourage effect; anxiety and other side effects of cannabis consumption; and more.*This content is never meant to serve as medical advice.* Support M&M if you find value in this content.* Full audio only version: [Apple Podcasts] [Spotify] [Elsewhere]* Full video version: [YouTube] [Odysee]* Episode transcript below.Full AI-generated transcript below. Beware of typos & mistranslations!Ryan Vandrey 2:59 empirical data buying some of the claims around cannabis, whether it's good, whether it's bad, or somewhere in between, and we try to be caustic to all of that and, and let our data do the speaking for us.Nick Jikomes 3:14 And do you guys work with humans animal models? What's your modality?Ryan Vandrey 3:18 So we in the lab here, there's a translational approach here. So there are some scientists part of the cannabis science lab that do preclinical work. And I personally do work with humans almost exclusively.Nick Jikomes 3:35 And so a lot of your work informs policy how, you know, before we get into the science of it, how direct is that connection? Do you work directly with policymakers? Or do you just sort of work in an area that's of interest to policymakers who you hope then read it? It'sRyan Vandrey 3:50 a little of both. And you know, when I started, I started out doing research with cannabis, it was only us doing things that we thought would be helpful. But you know, that's 20 years ago before widespread legalization or decriminalization, and changes in in retail marketplace really coming about. So it was pretty tangential. But now, you know, we're very intentional in monitoring and seeing what's happening and seeing what kinds of changes in the laws are being put forth and seeing changes in product types. And then we basically use that as a foundation for determining what kinds of research projects we think are the most important that what we go after. So, I guess to go back to your original question, you know, we do research that we believe is very helpful to policy and decision making and things like that, but we also have worked directly with legislators on Language in draft bills and legislation. I was part of a task force work group that helped design the medical cannabis law in the state of Maryland. And we've been called off by the FDA and other regulatory agencies to kind of come in and speak to what we've seen in the laboratory and how that might help them inform their policies and regulations at the state and federal level.Nick Jikomes 5:25 So you study cannabis, also known as marijuana, and it goes by many names. Obviously, you know, it's a plant people use it for recreational and medicinal purposes. As a scientist as a biology guy, how do you, what is cannabis to you? A lot of people think of it as being synonymous with THC, that from a chemical or pharmacological perspective, what is itRyan Vandrey 5:48 as I try to not even use the term cannabis anymore, because it's an umbrella term that 20 years ago was meaningful, in that if you said cannabis 97% of the time, we were talking about dried flowers of a plant that were rolled up and smoked, or stuffed into a pipe or a bong and smoked. And that was it. And it was always THC dominant in terms of chemical composition. But the reality is, once we opened up a retail marketplace, there are hundreds of different kinds of cannabis based products that exist now. And so I try as much as I can to talk about cannabis as a generality. But when we talk about specific things, and whether it's good, whether it's bad, how do you use it once the decision making, I try to be much more precise, because when we talk about those kinds of things, health impacts, we need to know what the primary chemical constituent is what the intended route of the stration is. And there's further nuance beyond that. But those are the two key things were I try as hard as I can to say, THC dominant cannabis CBD dominant cannabis CPG, dominant cannabis, and then talk about whether it's intended to be inhaled, orally ingested, topically applied, or some other manner of assumption.Nick Jikomes 7:24 And, you know, one of the things that's always been interesting, but also tricky from a research perspective, about cannabis, of any kind is, you know, is that it's, it's not one thing, people consume different types. And we have to be specific about what exactly the differences are. They consume it in different ways. The research historically has not always but often been. We often see researchers using preparations where subjects are consuming something like pure THC or something that is different from what people are using out in n

About the guest: Matt Kaeberlein, PhD is a Professor of at the University of Washington and CEO of OptiSpan. His research focuses on the biology of aging and longevity.Episode summary: Nick and Dr. Kaeberlein discuss: the biology of aging; mTOR, FGF1, growth & metabolism; sirtuins, NAD & NMN; longevity drugs like metformin & rapamycin; facts & myths about longevity molecules like resveratrol & taurine; controversies in aging research related to prominent Harvard researcher David Sinclair; epigenetic clocks; healthspan & lifespan; and more.*This content is never meant to serve as medical advice.* Support M&M if you find value in this content.* Full audio only version: [Apple Podcasts] [Spotify] [Elsewhere]* Full video version: [YouTube] [Odysee]* Episode transcript below.Full AI-generated transcript below. Beware of typos & mistranslations!Matt Kaeberlein 4:41 This is OptiSpan offices. And then right next door is or a biomedical so they're a company we spun out of my lab and as the U DUB. They do high throughput, longevity drug discovery using robots and worms. We can go take a look. Okay.Nick Jikomes 4:57 Yeah, that'd be great. That'd be great. Um, Just want to start off by telling everyone a little bit about who you are, what your scientific background is.Matt Kaeberlein 5:03 Sure. So, my name is Matt Kaeberlein, I am the CEO of OptiSpan, I guess I would describe optive span as a healthcare technology company. So our mission is really to create tools, technologies, protocols, to enable science based proactive preventative health care for as many people as possible. So we are very much of the belief that the current healthcare system is not as effective as it should be, to put it mildly. And that, really, it's it's centered around what I would call reactive disease care. Typically, we wait until people are sick before we try to do anything about it, then we try to treat their disease, we really want to help enable more proactive preventative health care, by both detecting disease early but more importantly, by empowering people to keep themselves healthy. And so I spent, you know, most of my career until about a year ago in academia, studying the biology of aging, I think that the biology of aging is certainly the most important risk factor for most functional declines, and diseases that people experience. So I think one aspect of this, you know, transition to what I call 21st century medicine with Peter Thiel would call medicine 3.0. I think targeting the biology of aging is an important part of that. But it's only part of it, there's also, you know, a huge component that involves screening for problems before they happen. And taking steps to ensure that we've sort of optimized our physiology as much as possible to maintain health. So I think you need all of those pieces. And that's really what we're all about here. So like I said, my background, really is I'm trained as a research scientist, and my entire career in research was spent trying to understand the mechanisms of biological aging. And why is it that all animals appear to undergo physiological decline as we get older? And what are the mechanisms and what aspects of those mechanisms are shared across the animal kingdom? With the expectation that the mechanisms of aging that are similar across the animal kingdom will be relevant to people? Yeah,Nick Jikomes 7:28 one of the things that's super interesting is if you take a comparative approach to aging, and you look across many different species, you think about this in evolutionary terms, all animals age, there's important differences between certain species. But something that's very interesting that I've talked with others about is there is this very lawful relationship between how long an animal lives how big that animal is, and its metabolic rate? Yeah, right. So small. This is why we talked about dog years. Yeah, we are dog's age faster than us. Small animals tend to age more quickly, they have shorter lifespans. How do you how do you think about that relationship? Why does that relationship exist? And what does that start to point us to?Matt Kaeberlein 8:11 Yeah, so great question. It's actually more complicated than that. Because when you look across species, what you said is true. smaller species tend to age more rapidly have have a higher metabolic rate than larger species. When you look within species, it's actually flipped. Smaller individuals tend to age more slowly. And we understand I think the mechanisms of within species variation based on body size pretty well. So we can get into that if you want to, I think we don't really understand the mechanisms for a cross species relationship between body size and longevity. So certainly, that sort of metabolic rate rate of living hypothesis is one hypothesis that's been around for a long time. Essentially, the idea there is that the faster you're burning metabolism, the more rapidly you accumulate damage associated with metabolism more rapidly

About the guest: Mark Bear, PhD is a Professor of Neuroscience at MIT, where his lab studies the visual system, neuroplasticity, and the pathophysiology of amblyopia and visual impairments.Episode summary: Nick and Dr. Bear discuss: the visual system in the brain, from the retina to visual cortex; critical periods of brain development; mechanisms of neuroplasticity; metaplasticity; amblyopia and visual impairments; ketamine & psychedelics; and more.*This content is never meant to serve as medical advice.* Support M&M if you find value in this content.* Full audio only version: [Apple Podcasts] [Spotify] [Elsewhere]* Full video version: [YouTube] [Odysee]* Episode transcript below.Full AI-generated transcript below. Beware of typos & mistranslations!Mark Bear 3:35 I'm a neuroscientist I'm currently hold the position of pick our professor of neuroscience at MIT. And we have been studying how experience modifies the brain for the duration of my career. And a lot of our recent work is really focused on trying to apply some of the knowledge that we've gained to correct mishaps of development that arise either from poor visual or experience or gene mutations.Nick Jikomes 4:11 And so when we think about the visual system, obviously, this is a sensory system that our body has that detects light. We have different sensory systems that affect different aspects of the physical environment in the retina of the eyeball. How is how is the nervous system actually detecting those photons? And what are some of the key features of those sensory neurons have that enable them to do that?Mark Bear 4:35 That's a That's a deep topic. And I will just tell you right off the bat, Nick, that I take a lot of what goes on in the retina for granted, for better or worse. Because most of our studies are focused on the cerebral cortex, which is the first place in the ascending visual pathway where information from the two eyes is combined. So we're very interested In the neural substrate of bind ocular vision, it's why, why we see one world with two eyes. And we can also see stereo, stereo scopic depth. But to answer your question, there photo pigments in the retina and specialized cells called photoreceptors, and they absorbed these photons. And there's a chemical change that ultimately results in a change in the voltage across the membrane of those photoreceptors. And as a result of that, membrane voltage change, there is a change in the release of a neurotransmitter, which is glutamate, common amino acid, glutamate. And then glutamate tickles the most direct pathways tickling another cell type in the retina called bipolar cells. And bipolar cells, in turn, talk to retinal ganglion cells and the retinal ganglion cells are the first cells in the retina that generate nerve impulses that then sweep up the optic nerves. And so it's the retinal ganglion cell activity. That is how we see. That's how the information gets from the eye into the brain.Nick Jikomes 6:16 So you said, you said that the visual cortex, which is going to be a number of synapses away from the retina, that's the first place that information from both eyes gets combined. And, and as you said, you know, we see one visual scene, I have one image in my mind right now. And yet, I've got these two channels of information coming from my left eye and my right eye. Can you give us a basic sense for what what is some of the key architecture and circuitry that is enabling that that that is the reason for why I have one image even though I've got these two separate channels of visual information?Mark Bear 6:50 Sure, yeah. It's, it's, it's a miracle of, of development and evolution, that these sort of these two rather independently developing structures that you eyes, giving rise to connections that somehow find their way into the brain, and they make a first relay in the part of the brain called the thalamus. And then these thalamic and in the thalamus, in most species, the information from the two eyes remains segregated. And then that information goes from thalamus through a projection to the visual cortex, which is, you know, the you can see it from the surface of the brain where the visual cortex is. And that is the it's neurons in the visual cortex of the first place where you find responses to stimulation of either eye. So there were strictly speaking by knock your now, just to contemplate for a second, how amazing it is, is that there, there's a mapping of points of visual space that talked to ganglion cells and either AI, and somehow those ganglion cells or the output of those ganglion cells, finds its way on a single target in the visual cortex. And the precision of these connections, while it's essential that these connections be precise, to serve by not your vision, and it sort of led to LED human weasel who were the real pioneers in studying the sending visual pathway to ask the question, is there a role for visual experience in this in the development of these very preci

About the guest: Kevin McKernan is the Chief Science Officer at Medicinal genomics and has been working the the biotechnology sector and conducting genomics research going back to his involvement in the Human Genome Project.Episode summary: Nick and Kevin discuss: basics of DNA and RNA biology; mRNA vaccines and how they work compared to traditional vaccines; the mRNA vaccine manufacturing process; DNA contamination in the Pfizer and Modern mRNA vaccines for COVID; the SARS-CoV-2 spike protein; vaccine side effects; ivermectin and hydroxychloroquine; and more.*This content is never meant to serve as medical advice.* Support M&M if you find value in this content.* Full audio only version: [Apple Podcasts] [Spotify] [Elsewhere]* Full video version: [YouTube] [Odysee]* Episode transcript below.Full AI-generated transcript below. Beware of typos & mistranslations!Kevin McKernan 4:21 Was that Senator Ron Johnson humble hearing on all those COVID stuff. So you had myself Malone, Jessica Rose, Pierre quarry. long list of people who were just presenting evidence and all of the shenanigans going on in COVID. Yeah,Nick Jikomes 4:42 we're gonna talk about a lot of that, I guess here. Why don't we just start off with some basic stuff. Want to don't you just tell everyone a little bit about yourself, your background, your expertise, and you know what you do at a high level?Kevin McKernan 4:57 Okay, sure. Um, so My background started in, in this field in 1995. Actually on the Human Genome Project, I was started there as a member of the research and development team and shortly thereafter to the folks leading it left and left me in the reins, wholly unqualified, and I had to learn on the fly. So I started managing that research and development group to about a probably a 10 or 12 person group inside the Whitehead Institute Center for Genome Research was under Eric Lander and Lauren Lintons guidance. And we built basically the robotic platform and the DNA purification system to purify. We did about 20 million plasmids a year on that thing to do Sanger sequencing for the Human Genome Project. So, my role there was was related to the automation and the DNA purification chemistry and optimizing all the Sanger cycle sequencing stuff. And zash as that project came to a completion a lot a lot of companies were asking how to export that technology and and MIT held some patents on it. So we licensed those and spun them out to a company called Agincourt which became a really large DNA sequencing company. Actually, it was the largest commercial sequencing entity I think in the in the world. By probably 2004. Beckman came to acquire it in 2005. We had beyond just a DNA sequencing facility, it was a we had a bunch of DNA purification technology that was used to purify viruses and a variety of pathogens from blood. So they acquired that but in the process, there was a skunkworks project, we had to build a DNA sequencer that used us to sequence DNA off of single magnetic beads. And that was starting to show some promise, but of course, no one knew how to value it at the time, and so they decided to split it out into its own company called Agincourt personal genomics. And a year later, we presented data sequencing a coli genomes at Eygpt, which caught the attention of ABI and Illumina who proceeded to have a bidding war over the company. And Avi eventually won that bid and purchased Agincourt personal genomics and brought the solid sequencer to market. So I spent from 2006, to about 2011, working at EBI, getting this all sequencer to market. And we also at towards the end of that acquired Ion Torrent, which was another next generation sequencing system that worked on semiconductors. So I worked on that program, helping get that developed and out the door and then decided to split ways and worked on some other passions of mine, one of which was the cannabis genome I had been, I had a very large non compete, the company was now part of life tech, which is a bigger entity, which meant I couldn't really compete. My non compete man, I really couldn't work in that space. So I kind of just went off into the Ag space. And we started sequencing cannabis genomes, because we felt they were the genome had been sequenced at the time, and it had all these therapeutic compounds in there that could be helpful for cancer. And so we figured let's get the thing public and see if that helps kind of mature that field. That field got a little complicated. As you might imagine, growing a business in the cannabis field is difficult from a banking perspective, and the laws keep changing on you. So the company kind of pivoted back into doing clinical sequencing of people who might benefit from cannabinoids, so a lot of epilepsy patients mitochondrial disease patients, autism spectrum disorder. So we were doing exome sequencing on those cohorts as a clinical test. And that went on for about five or six years before we realize that cannabis market started to evolve

About the guest: Luc van Loon, PhD is a Professor of Physiology of Exercise and Nutrition and Head of the M3-research group at the Department of Human Biology at Maastricht University. His lab focuses on the skeletal muscle adaptive response to physical (in)activity, the impact of nutrition on metabolism, and related topics.Episode summary: Nick and Dr. van Loon discuss: amino acid biology; branched chain amino acids like leucine; atypical amino acids like taurine; muscle growth & muscle biology; dietary protein and plant vs. animal protein sources; resistance training and anabolic growth; the limits of dietary protein on muscle growth; and more.*This content is never meant to serve as medical advice.* Support M&M if you find value in this content.* Full audio only version: [Apple Podcasts] [Spotify] [Elsewhere]* Full video version: [YouTube] [Odysee]* Episode transcript below.Full AI-generated transcript below. Beware of typos & mistranslations!Luc van Loon 3:25 Oh, I think that's the publication's actually, it's, it's as normal, but I think this one got a lot of attention by worksheets. And it seems that we're publishing more. I think I've always been publishing but mostly we do not mean I don't I do not tend to send it to high impact journals. Because I generally prefer to send it either to the exercise people or the nutrition people. So they often come up in lower impact journals, which doesn't mean the quality is anything less of that. But you want to formula was the lead author of this really wanted to send it off at a high impact journal. He's young and ambitious, I've already lost that stage. doing that. That's why a lot of attention.Nick Jikomes 4:09 Do you feel like you actually get better reviews, higher quality reviews when you send it to more like specialty journals rather than, you know, the top to your sexy big name journals?Luc van Loon 4:22 I think a lot of the the higher impact journals is a lot of who knows who. And also a lot of combination studies where for example, human and animal work and a lot of cell work are combined. And sometimes that makes sense for some studies. For some studies, it's absolutely doesn't make sense. Because sometimes those three models are not they don't mean they do not necessarily align.Nick Jikomes 4:50 Yeah, I guess I mean, yeah, there's probably a lot of ways that you know, a mouse mouse has metabolism works very differently than a human's. And if you try and compare them you're you're trying to fit a square, you know, a square peg into a round hole. Yeah, oneLuc van Loon 5:04 major problem that you have, for example, we got this, this this question a lot that, for example, we show for example, protein synthesis, or amino acid uptake or perfusion or, or anything that is directly measurable as a dynamic measure, like muscle protein synthesis over the last few hours, blood glucose uptake or release from the liver, stuff like that, that we do with stable isotopes, that gives you a real physiological signal of a process that is ongoing. And then often we get responses like, Oh, you haven't shown a mechanism. And then I say, I'm just thinking like, we've just show you showing you the mechanism, because that is the effect that has on glucose uptake, blood perfusion press, protein synthesis, whatever. And then what they want to see is, for example, a whole scholar of mRNAs, or western blots or phosphorylation of specific proteins. And to be honest, I'm not very in favor of that, because it only gives you snapshots of what happens at a certain point in time, because that's only one biopsy. One time point that shows you light, x is on light, y is off, that doesn't give me any mechanism and gives me only an insight that there are a few proteins that might be relevant, or really have a relationship and a process that I was looking for. So I'm always a little bit pissed off when I hear somebody saying, like, you have to do molecular signaling in order to get a mechanism. That's that's absolutely not what I think.Nick Jikomes 6:32 Yeah, I mean, what what you're speaking to, I think, is, it's a pretty deep problem in that, what you're really saying is the language scientists use, we often use language in different ways. So you know, when a molecular biologist says mechanism, and they have a background in transcription, they want to see gene expression patterns. When someone like use this mechanism you have you have something different in mind. And people often sort of, frankly, when people ask for mechanism, oftentimes not always, certainly, but oftentimes, it's kind of just a lazy lazy assessment, saying, yeah, just show me what I'm familiar with. Yeah. AndLuc van Loon 7:09 so the the main thing that we do, and that's not because we're preaching for our own ministry, but we use a lot of stabilized setups, and why, because we can see the dynamics in a process and nothing in the body is regulated, on a simple concentration, everything is regulated on changes in uptake, r

About the guest: Tommaso Di Ianni, PhD is an Assistant Professor in the Departments of Psychiatry & Behavioral Sciences and Radiology & Biomedical Imaging at the University of California, San Francisco. His lab uses ultrasound technology and deep learning to study the brain.Episode summary: Nick and Dr. Di Ianni discuss: the current state of scientific understanding of ketamine; S-ketamine vs. R-ketamine isomers; the antidepressant effects of ketamine; ketamine's known mechanisms of action; sex-dependent effects of ketamine action in the brain; involvement of the opioid system in ketamine's effects; addiction; and more.*This content is never meant to serve as medical advice.* Support M&M if you find value in this content.* Full audio only version: [Apple Podcasts] [Spotify] [Elsewhere]* Full video version: [YouTube] [Odysee]* Episode transcript below.Full AI-generated transcript below. Beware of typos & mistranslations!Tommaso Di Ianni 3:59 Reaching out I was actually listening to your podcast quite a bit when I was commuting to Stanford. So that wasNick Jikomes 4:05 ah, which which ones did you listen to?Tommaso Di Ianni 4:08 Oh, I listened to Alex Kwan. Listen to Gul Dolan more recently. I listen to Christian Luschiar. Oh,Nick Jikomes 4:19 yes. Yes, I am. Maybe going to ask you about some of that work and how it connects.Tommaso Di Ianni 4:24 Yeah, yeah. I listen to quite a few.Nick Jikomes 4:28 Excellent. Yeah, no, I'm glad to hear it sometimes. I'm starting to hear that more. Which is, which is a nice surprise. Yeah, yeah. That's nice. Yeah. Because sometimes because you know, when I first started, I was you know, essentially emailing people, and they have no idea who I am. But sometimes now they're like, Oh, yes, yes. I listened to this episode. So I already know you. Nice. Yeah. Do you want to just start off by introducing yourself telling people a little bit about your your scientific background and what your lab is doing now?Tommaso Di Ianni 4:57 Sure. Yeah. So I am the master of the art. Me I, I'm an electrical and biomedical engineer by training. And then I did a postdoc at Stanford, I was in the Department of Radiology. But I was really working at the interface of ultrasound and neuroscience. So my background is mostly in ultrasound. So both ultrasound imaging and therapeutic ultrasound. And when, during my postdoc at Stanford, I started applying these modalities to neuroscience. And more recently, I started, we started develop both developing and applying kind of develop developing technological innovations and applying this modality called functional ultrasound imaging to studying pharmacology and studying how drugs act on the brain and more specifically Academy, which is what we're going to talk about today.Nick Jikomes 5:59 Yeah, let's, let's start off by talking about some of the technology here. So you're using ultrasound to do imaging. Normally, when people hear ultrasound, they think about a pregnant woman going in for her ultrasound to get those first images of the baby. Can you give us an overview of how exactly ultrasound technology works? And what some of these other applications are beyond? Beyond the familiar one? Yeah.Tommaso Di Ianni 6:23 So the imaging is really not much different than what happens when when Yeah, the one of the applications, the one you mentioned, for fetal imaging. But what we're really looking at here is blood flows. So ultrasound is also imaged. So people may also be familiar with applications like color flow mapping, like when you're imaging an organ like the liver, for example, or the the neonatal brain, or the arteries, for example, in the neck, and you see those blue and red colors, overlaid on the image, those those colors show a measure of blood flows. And so in the application that we are using there is again called functional ultrasound imaging, we are the kind of the underlying technique is called Power Doppler. So we are doing Doppler imaging and imaging blood flows. Now, if we have one single image of the blood vasculature like that blood flow, that's just giving us a snapshot of the vasculature at that specific time point. But what do we do here, we track those blood flows over time. And there is a principle that is the principle that is underlying all this is called neuromuscular coupling, which is telling us that essentially, the brain has no intrinsic ways to store energy and oxygen, and therefore if there is an increase in activity locally, the way these cells can get the supply of oxygen and glucose that they need is by recruiting more blood. So if we track those blood flows, we can indirectly infer neural activity. So this is not dissimilar to what happens with other modalities like fMRI for exam functional magnetic resonance imaging. Yeah, soNick Jikomes 8:25 a chunk of neuronal tissue becomes more active. It could be excitatory cells, it could be inhibitory cells could be both, but they're becoming more active, they require more energy to

About the guest: Scott Zimmerman is an optical engineer and photobiology expertEpisode summary: Nick and Scott talk about: how light interacts with the body and affects our cells; melatonin as an antioxidant; how red & near-infrared light affect mitochondria; sunlight, fire light, and artificial light; incandescent light bulbs vs. LEDs; negative health effects of artificial light; sunscreen & makeup; red & near-infrared light therapy; the optical properties of the human body; and more.*This content is never meant to serve as medical advice.* Support M&M if you find value in this content.* Full audio only version: [Apple Podcasts] [Spotify] [Elsewhere]* Full video version: [YouTube] [Odysee]* Episode transcript below.Full AI-generated transcript below. Beware of typos & mistranslations!Scott Zimmerman 5:08 about your background, I looked a little bit but I didn't guess, get a follow up date on.Nick Jikomes 5:14 Yeah. Um, so my background is in research science. So I did a PhD in neuroscience. And I was a researcher for a number of years, and then moved into the technology sector in the cannabis industry, actually. And I worked in that for a number of years. And now I pretty much just do this and some consulting advisory work on the side. But I've been, you know, I've been interested in learning more about the effects of light. Beyond the obvious, obviously, we have a visual system that allows us to see things that's actually partly what I did my PhD research, and we all know about UV light, and it's mutagenic effects. And, you know, that's the reason why we we are so often wearing sunscreen, but it's only been fairly recently for me that I've come to learn more and appreciate that, you know, the other wavelengths of light are also having really interesting physiological effects. And you seem to be a good person to talk to you about that.Scott Zimmerman 6:13 Well, you know, it's, I think it's an amazing field, to be quite honest, it hasn't really been tapped into very well. I mean, there's been a lot of work done on photobiomodulation, and red light therapies and things of that nature, that got some of that kind of mixed reviews from the medical community, and all that. But I, what I was amazed is that there really wasn't, I'm an optics guy, you know, so I was just amazed that there was so little known about the differences and the similarities there are, you know, in the body and how it functions optically, especially in the near infrared, because you have such, you have to move from a two dimensional to more of a three dimensional way of looking at it, because there's so much penetration and propagation that occurs at some wavelengths. And I think, have you seen Bob Fosse Berry's pictures in the near infrared of the hand and think, no, no,Nick Jikomes 7:07 I don't think so.Scott Zimmerman 7:09 When we get done, I'll ship it to you ship you some pictures. But what you start to find out is, is that, on an optic standpoint, we're pretty infinitesimal in our infant in our maturity of our ability to even measure are to measure or to essentially, model how light propagates in the body. And unfortunately, most people go and they grab a cadaver or sheep's head, and they put a laser on the outside and they measure, put a detector on the inside and say, Oh, you only get 5% transmission? Well, that's, that's a bogus way of making the measurement, it doesn't actually work. That way, when you're dealing with scattering volumes, it's one of the hardest measurements to make and optics there is. And so what happens is, is that I like to give people kind of an analogy, you know, if you put an ice cube, a nice clear ice cube, in front of that laser, and you have a detector sitting back there, then you get almost all the light 100, almost 100% transmission less the for now losses. If you take that same size, and you make it a snowball, that's an ice cube, same size, you shine the laser and do it, the entire thing lights up, and the transmission goes down to next to nothing. Because what happens is most of the light is scattering into the volume and changing its direction and reflecting back twice knows why and all this other great stuff. So, you know, unfortunately, to try a model that is extremely complex and hard to do. And really, we lack a lot of the body is a lot farther along and you're doing optics in the body than than we are and our ability to actually model it and understanding.Nick Jikomes 9:00 Yeah, yeah. Yeah, that makes sense, right? I mean, we've we've been interacting, as, you know, creatures walking the earth, we have a very, very long evolutionary history with the sun present as a huge environmental stimulus. And so our bodies have adapted to it and, you know, figured out so to speak, how to respond to and utilize that light in ways that are beyond our, you know, beyond our ability to model it as as you said, Yeah,Scott Zimmerman 9:29 well, and and, unfortunately, there's been some pretty sloppy, myself incl

About the Guest: Bruce Blumberg, PhD is a Professor of Cell & Developmental Biology at UC-Irvine. HIs lab studies epigenetics, gene x environment interactions, hormones & endocrine disruptors, obesogens & environmental toxins, and more.Episode Summary: Nick and Dr. Blumberg discuss: Embryonic development; hormones and hormone receptors; estrogen & xenoestrogens; environmental toxins, obesogens, pesticides & contaminants; environmental causes of obesity; microplastics; how to avoid toxins in food & drinking water; and more.*This content is never meant to serve as medical advice.* Support M&M if you find value in this content.* Full audio only version: [Apple Podcasts] [Spotify] [Elsewhere]* Full video version: [YouTube] [Odysee]* Episode transcript below.Full AI-generated transcript below. Beware of typos & mistranslations!Bruce Blumberg 4:45 I'm a professor of developmental cell biology primarily at the University of California Irvine. And I started out as a developmental biologist and just trying to understand how does pattern form in in the embryo how does the embryo and able to self assemble to make a correct version of you or me or of your cat or your dog or whatever you have at the program is inside the embryo to develop that structure. And during the process of studying that I became interested in the role of small molecules that could activate hormone receptors on development. A great example of important molecules like that is retinoic acid, which is very important patterning molecule in early development. And from there, I began to look at molecules that looked like receptors, but we didn't know what the hormones were the bounds of those. So we call those in those days orphan receptors. And eventually, in studying those, and continuing our work in developmental biology, I realized that the intersection of identifying hormones for orphan receptors and developmental biology was the field of endocrine disruption. So that is, how do chemicals that we encounter in our diet and our environment affect the function of endocrine system? It turns out, there's quite a lot that do that. And we unexpectedly found a chemical that could make animals fat about 10 years ago, 1011 years ago now. And we decided to call such molecules obesogens. So we've been working on obesogenic endocrine disruptors, for the most part ever since then, for almost the past 20 years, now,Nick Jikomes 6:28 I want to spend a little bit of time upfront talking about some, some basic biology, get some concepts in people's heads. So I want to talk about hormones. So what exactly are hormones? And how are they different from just other types of signaling molecules that that make our biology tick.Bruce Blumberg 6:48 So classically, hormones are defined as molecules that enter the blood in one place, and act at some distant place. That's the classic endocrine hormone, for instance, cortisol or a straight die, or testosterone, or thyroid hormone. Those are the classic endocrine hormones. And these hormones Act are receptors that live in the nucleus of the cells. Okay, where they act as switches to turn genes on to turn genes off. And that's distinguished from other kinds of receptors, for example, a classic example would be insulin, so insulin access to a receptor on the cell surface, that triggers a cascade of secondary signals inside the cell that eventually has an effect in the nucleus to turn genes on and turn genes off. So the nuclear hormone receptors that we work on, have many less intermediates between the circulating hormone and the effect on gene expression.Nick Jikomes 7:45 And so because because they're binding to these receptors in the nucleus, as opposed to ones that are on the cell membrane, Does that just mean that they can have a more sort of direct and fast action on changing gene expression?Bruce Blumberg 8:02 More direct effect? Yes. I don't know if anyone's ever, ever contrasted how fast the action is, I would say they're both probably so fast that the difference isn't meaningful. And that they're less intermediates. Okay,Nick Jikomes 8:17 so they actually get inside of cells get inside the nucleus act on receptors there. And so there's there's less in between them, and changes in gene expression, than there would be if we were talking about a molecule like insulin that's binding to a receptor on the outer cell membrane,Bruce Blumberg 8:34 which has two or three or four intermediates. Now there's, there's nothing wrong with having intermediates, right. They provide a way to amplify or modulate the signal, and for the pathways to interact with others. Just saying it's different,Nick Jikomes 8:48 I say, and is this the the bit about nuclear receptors? Is that baked into the definition of hormones? Or are their hormones that also interact with receptors on the membrane? Yeah,Bruce Blumberg 8:59 so we're getting a little complicated now. So there are the nuclear hormone receptors. These are receptors for hormones that act insid

About the Guest: Clare Bryant, DVM is a Professor of Innate Immunity at Cambridge University. Her lab studies the innate immune system, pathogen detection, inflammation, and chronic disease.Episode Summary: Nick and Dr. Bryant discuss: mechanisms of inflammation; inflammasomes & fatty acids; infection & disease; innate vs. adaptive immunity; chronic inflammation; allergies & allergens; the evolution of the immune system; anti-inflammatory effects of fasting; and more.*This content is never meant to serve as medical advice.* Support M&M if you find value in this content.* Full audio only version: [Apple Podcasts] [Spotify] [Elsewhere]* Full video version: [YouTube] [Odysee]* Episode transcript below.Full AI-generated transcript below. Beware of typos & mistranslations!Clare Bryant 4:41 sure. So I am Professor of innate immunity at the University of Cambridge in the United Kingdom. So what that really means is that I am really interested in studying the front line mechanisms that fight pathogen infections so predominantly bacterial infection In my case, and in particular, I'm really interested in understanding zoonotic infections. So I after COVID, I don't really have to explain what a zoonotic infection is anymore. I will do, but I used to have to make a big song and dance about this, but basically, infections that are tolerated by animals, but that jump into people, sometimes these infections cause disease in animals, but more often than not, they don't. And I'm really interested in understanding the immune mechanisms that allow these infections to be tolerated by the animals. Yet when they come into people, they cause inflammatory and infectious disease. And actually, from this, I've been, I've been led on to work on a number of sterile infectious diseases that includes Alzheimer's disease, obesity, and a variety of other problems, which is been kind of an interesting migration for somebody because actually, I was trained as a veterinarian, and I find myself working on a host of diseases that affect humans as well as animals.Nick Jikomes 6:02 Okay, so So you were actually trained as a veterinarian? Yeah, that's, that'sClare Bryant 6:05 correct.Nick Jikomes 6:06 What, how to? So you went to vet school, but you're basically doing basic research how to how did that happen? I think that's pretty unusual.Clare Bryant 6:14 Yeah, it is unusual. So it was, yeah, it was an interesting career track, really, because I wasn't really what I anticipated doing. Although I was very, I did a primary basic training and physiology and biochemistry and did some research then and, and really got excited by the concept of research, I did a summer vacation job, in fact, which really was like a lightbulb moment where I thought, oh, research, this is really interesting. But I went on to do my veterinary degree and complete the training. And what I appreciated very early on was that whilst I found animal disease fascinating, and the patients are really cool, sometimes the owners are a little bit more difficult, which is why I trained to be a wrestler, not a medic. But what was very frustrating for me was that in the clinic, I couldn't really get to a molecular answer. And I realized I really did need to understand a really fundamental basic mechanistic answer, and I was not going to get there in clinical practice. And so that there really decided my career for me, because from that point on, I thought, Alright, I need to understand mechanisms. And that requires me really digging into the research to understand what's going on. And so from that point, on my career track was sort of defined and determined to be really basic biomedical research.Nick Jikomes 7:42 And so Professor of adaptive immunity, or excuse me innate. Yeah, myClare Bryant 7:51 question here is very important. Yes.Nick Jikomes 7:53 In fact, I think it would be good if you explain for people, what's the difference between innate and adaptive immunity? Yeah,Clare Bryant 7:59 for sure. So, innate immunity is the first line of defense. So what happens is when a pathogen enters the body, it will encounter initially a set of barriers. So it's things like your mucosal barrier in your lungs or your gut, it will then encounter a set of sort of primary immune cells, for example, neutrophils and macrophages, and the job of those cells is to is to see the pathogen and try and kill it. And, and the specificity there comes from receptors or proteins in the cell membrane that allow you to detect pathogens and discriminate that has been different from the host. And what these cells also do is send out signals to recruit adaptive immune cells. So this is things like T cells and B cells, which provide the memory and repeat response. When a pathogen comes along again, these cells are recruited, they talk to things like the macrophages and a special set of cells called dendritic cells. And this interaction then between naive T or B cells, T cells route between naive T cells and dendrit

About the Guest: Guillaume (Will) de Lartigue, PhD is a neuroscientist at the Monell Chemical Senses Center. His lab studies the neurobiology of eating, including how the vagus nerve senses internal stimuli in the gut.Episode Summary: Nick and Dr. de Lartigue discuss: gut-brain communication; the vagus nerve; gut hormones like leptin & GLP-1; weight loss drugs like Ozempic; glucose vs. fructose vs. non-caloric sweeteners; how the vagus nerve connects the gut to the dopamine reward system in the brain; the sensation of fats and sugars in the gut; food addiction & obesity; and more.*This content is never meant to serve as medical advice.* More M&M content about diet & metabolism.* Support M&M if you find value in this content.* Full audio only version: [Apple Podcasts] [Spotify] [Elsewhere]* Full video version: [YouTube] [Odysee]* Episode transcript below.Full AI-generated transcript below. Beware of typos & mistranslations!Will de Lartigue 6:02 So I'm an associate member at Manal Chemical Senses center. And I have an appointment at University of Pennsylvania in the Department of Neuroscience. And I guess my background, I studied the neurobiology of feeding.Nick Jikomes 6:24 And so what I want to talk about today, basically, if I sort of what I'm envisioning here is the biology of feeding after food is swallowed, and gets gets past the tongue. And so you know, one of the interesting things, one of the interesting pieces of biology here is that, you know, the body can sense what we eat, and how much we eat in various different ways. And so, you know, obviously everyone has experienced eating food, we know that it has taste, we can taste sweet things, and sour things and savory things. But there's some interesting biology and some interesting, you know, sensory biology that's happening after we swallow our food that allows our brain to know what we actually ate. And so to start off, can you just start talking about what are some of the major ways that the gut is communicating with the brain? You know, I know that there are nerves that are coming down from the brain to the gut, the gut is releasing hormones that circulate in the bloodstream and go back up to the brain. What are the basic kinds of ways that gut brain communication happens?Will de Lartigue 7:26 Well, that's a very big topic right there. But essentially, food comes into the stomach. And the amount of food that we consume is sensed through the stretching of the stomach itself. And that information can be relayed to the brain in multiple different ways. The main way is that there's different nerves like the vagus nerve, for example, that is probably the longest and biggest nerve in our body innervates, all the different organs. And it highly innervates the stomach in the intestine. And so when these nerve terminals and stomach, feel the stomach expand as we get more full, that sensation is, is triggers the vagus nerve and signals to the brain that there's food in the stomach, and it kind of gives us some information about the amount of food that we've consumed. And then the food kind of gets broken down, and it gets into our intestines where it gets absorbed. And there, there's two things that happen. So the the cells that line, the intestine will release hormones, as they sense the different types of nutrients, those hormones can enter into the circulation and act directly on the brain. Or they can act in a paracrine manner, which means that they're just being released from the cells and activating the nerves that are nearby. And then the vagus nerve can also signal to the, to the brain that way, and then the intestine content, information about again, stretch, so how much the quantity of food that's reaching the intestine, but also the different types of nutrients. So fats, sugars, proteins, that are actually in the intestine is getting broken down and absorbed is also being sent to the brain. So there's a lot of information in response to a meal that gets processed at the level of, of the gut, and that gets sent to the brain.Nick Jikomes 9:36 So the nervous system can actually detect that something's in the stomach of the GI tract. And not only that, get information about what's in there before it's all those nutrients are even fully absorbed and circulating throughout the body.Will de Lartigue 9:49 Yeah, and it's so it's thought that the stomach doesn't really process the types of food that we have more the volume of food and then the intestine probably does a little bit of both and the combination of those informations, then lead to different types of behavioral consequences. So when you feel stretch and you feel full, then it makes you stop eating. But when you sense the nutrients that can sit maybe to some degree control food intake, but we think it's more dictating what types of food we want to eat and actually causing reward that might prolong the meal or increase the rate at which we're eating that meal. SoNick Jikomes 10:26 so there's this

About the Guest: Nicolas Glynos, PhD received his doctorate in Molecular & Integrative Physiology from the University of Michigan, where he studied the psychedelic drug DMT in the mammalian brain.Episode Summary: Nick and Dr. Glynos discuss: the history of DMT research; the use of DMT in ayahuasca; whether DMT is found endogenously in animals; why plants produce DMT; pineal gland, DMT & melatonin; the latest research looking at the presence and effects of DMT in the brain; and more.*This content is never meant to serve as medical advice.* More M&M content about psychedelic science.* Support M&M if you find value in this content.* Full audio only version: [Apple Podcasts] [Spotify] [Elsewhere]* Full video version: [YouTube] [Odysee]* Episode transcript below.Full AI-generated transcript below. Beware of typos & mistranslations!Nicolas Glynos 4:33 Hmm, yeah, so I finished a PhD in Molecular and integrative physiology at University of Michigan last May, so almost a year ago now. And my PhD work was focused on DMT. Primarily, we looked at endogenous DMT and how its regulated in different functions of endogenous DMT. And then we also explored some different aspects of exile. Initially administered DMT in a rodent model. I also contributed a lot to psychedelic education and activism at Michigan during my PhD and published some papers on naturalistic psychedelic use and looking at interactions with healthcare providers and changes in outcomes reported by people using psychedelics naturalistically. And currently in a postdoctoral role, also at the University of Michigan, and in the chronic pain and fatigue Research Center. And there we have a group that's working on various Psychedelic Studies, and we're currently running a clinical trial with psilocybin treating patients with fibromyalgia, if.Nick Jikomes 5:46 Interesting. So. Yeah, I read some of your work looking at DMT, endogenous DMT and the effects of exogenous DMT, and rodents, which is very interesting. Can I just want to give people a little bit of a background in terms of what DMT is and what was known about it before getting into your work? So can you give people like a cliff notes on like, what is DMT? Chemically? How is it different from other psychedelics?Nicolas Glynos 6:15 Yeah, I think DMT is the most interesting psychedelic, and that was my passion when I came into graduate school was to get involved in DMT research. It's a pretty simple molecule. It's structurally similar to the neurotransmitter serotonin. It's also structurally similar to other psychedelics like psilocybin. And it's, it's a tryptamine and that's the chemical class that it belongs to. And it's, it's dime, it's got two methyl groups attached to the to the Amino part of the tryptamine making it Dimethyltryptamine. And it's got it's got an interesting history and actually a pretty long history in terms of terms of relative to other psychedelics. It's an active component in the hallucinogenic brew ayahuasca, which has been used across South America in various indigenous cultures for at least 1000 years. And I Alaska is a very important ceremonial and medicinal brew that's been that's been consumed widely across across South America. And DMT was brought into sort of Western science in the early 1900s. It was discovered in 1931 by a chemist named Richard Mansky, and he discovered it and it was kind of set aside before it was investigated any further. And it wasn't until I think it was 1955. Steven Psara chemist in Eastern Europe, was interested in reports of ethnographers that were studying plant based hallucinogens in South America, and they were bringing plants back and they were curious what the active compounds in the plants were that were causing these hallucinations and these psychedelic experiences, and it was found that DMT was a high a candidate for for that molecule to be the the psychoactive compound. So he administered or began the first clinical trial or the first western science research trial with DMT. And he administered it intramuscularly, first to himself and then to participants, and found that it was indeed, hallucinogenic and psychedelicNick Jikomes 8:30 himself with what's app, how much did he give himself?Nicolas Glynos 8:33 I don't remember the dose exactly, but but I'm sure there was quite a bit of trial and error, because I think, you know, obviously, you would probably try an oral administration first. And I believe he did that and found that DMT wasn't orally active, and then had to go the intramuscular route to to to get the to get the effects. So that kind of brought some interest into this molecule into this compound, as a psychedelic compound. And this was also kind of occurring around the time when LSD was was being investigated in a research context, and in a clinical context, and also around the time of the discovery of serotonin as a naturally occurring endogenous compound that has has effects on mental states and mood and various other physiological

About the Guest: Terrence Deacon, PhD is a Professor in the department of Anthropology at UC-Berkeley. He has written many papers and multiple books about the evolution of human language, origins of consciousness, and related topics. Episode Summary: Nick and Dr. Deacon discuss various aspects of biological evolution, from natural vs. sexual selection to gene duplication and the consequences of domestication; the domestication of dogs and songbirds; human vs. non-human forms of vocal communication; ritual behavior & the origins symbolic cognition; artificial intelligence & large language models (LLMs); and more.*This content is never meant to serve as medical advice.* More M&M episodes with Terrence Deacon.* Support M&M if you find value in this content.* Full audio only version: [Apple Podcasts] [Spotify]* Full video version: [YouTube] [Odysee]* Episode transcript below.Full AI-generated transcript below. Beware of typos & mistranslations!Terrence Deacon 4:12 Oh, yes, I'm in the middle of a book called fouling up. How inverse Darwinism catalyzes evolutionNick Jikomes 4:21 what is what is inverse Darwin Darwinism. SoTerrence Deacon 4:24 everybody asks, it's actually not anti Darwinism. It's a compliment to Darwinism. And I think it's a compliment that was there. In Darwin's own writing, though, he doesn't recognize it. And that's why I've used the phrase. So Darwinism in 1838. He came up with three ideas to send his chose up his notebook that basically drove the rest of his thinking. And it came up right after rereading or I don't know, they read the whole thing before this, but certainly reading Malthus on population this this whole problem Malthus realizes is that reproduction outpaces resource. And Malthus, of course, had this dire prediction that this would lead to terrible things in England in Europe. Because populations were growing so fast and resources were not growing fast enough. Darwin sees this and says, aha, but in the natural world, this is going to be the case. And that means there's going to be selection that favors a few over the others. Those that fit better with the contexts that can do better, they can outpace the others. And so this sort of drives his theory. And he comes up with three ideas, he says, the first thing is that I noticed that everybody realizes that the grandchildren are like grandparents, as basically they traits are inherited, they're passed on down. And he says, but but in fact, the second thing is that there is great variety and offspring. That is, although they carry some of those traits as a lot of variety. So that's a second story. That's a variation problem. Then the third one is, he says, But you know, then there's, there's great overproduction with respect to support of those offspring. And but those three things together, and you get natural selection. That's Darwin's basic idea. But notice that the Malthusian part isn't necessary. And it was what gave him the insight for natural selection. But if you think about things like gene duplication, that happens all the time in evolution, in fact, whole genome duplication does happen, particularly in plants. What happens is that the excess production doesn't necessarily mean that you're outstripping resources, doesn't take a lot of energy to produce extra genes, or to have a single gene that's duplicated, like in transpose on effect, there's not much energy use, but even in terms of multicellularity, think of the production of multiple cells, the reproduction by mitosis. Now, that builds a large multi cell body with maybe trillions of cells. There's some contexts in which some of those cells are in competition with each other, but not often. Usually, it's a context in which there's no competition, which is excess resources, in which overproduction is in fact, the way life has to work. In fact, to stay ahead of the second law of thermodynamics, you can't just repair things, you have to make extras, you have to have backups, you have to have duplicates, because something's gonna go wrong, eventually, we know that in terms of our own computer technology, that you got to have backups, you got to make copies of things. And that's how you keep things going. Well, evolution, of course works. But what happens when you don't have competition? When you don't have this subtractive effect, if you think about it, natural selection is a subtractive process. It requires variation. But it also requires overproduction. You have to make more than you need because you're gonna get rid of some.Nick Jikomes 7:59 Yes, so you're taking away individuals who are unmatched to their environment, and leaving behind those that are better matched to their environment. But But I think I see where you're going here. If you think about something like gene duplication, that's not happening at all, you're just adding a new thing. And then that redundancy gives you space to evolve a new function without any actual competition thereTerrence Deacon 8:21 ex

About the Guest: Robert Lustig, MD is a physician-researcher and expert of metabolic health. He is Professor emeritus of Pediatrics, Division of Endocrinology at the University of California, San Francisco (UCSF), specializing in neuroendocrinology with an emphasis on the regulation of energy balance by the central nervous system. His research and clinical practice has focused on childhood obesity and diabetes.Episode Summary: Nick and Dr. Lustig discuss the true causes of obesity and metabolic discussion; how the in utero environment during pregnancy leads to multigenerational effects on health; different forms of sugar like fructose vs. glucose; different dietary fats like omega-6 and omega-3 PUFAs, and saturated fat; oxidative stress & mitochondria biology; how temperature, altitude & oxygen affect obesity; processed foods and how industry influences public perception; body positivity & public education; insulin, diabetes & fatty liver disease; statins & cardiovascular health; and more.*My content is never meant to serve as medical advice.* More M&M content about diet & metabolism.* Support M&M if you find value in this content.* Full audio only version: [Apple Podcasts] [Spotify]* Full video version: [YouTube] [Odysee]* Episode transcript below.Full AI-generated transcript below. Beware of typos & mistranslations!Robert Lustig 5:20 loaded question, Nick, to say the least, we've learned in the last 30 years about a new aspect of medicine. And it's called the developmental origins of health and disease or DOHaD. The first person to notice this was a epidemiologist working in Southampton, England, by the name of David Barker. And he was basically going through records of people who were born during the war during World War Two. And notice that these people were dying early. And he didn't know why. And, you know, it was years later that he noticed this. And he did an enormous amount of exculpatory work that to this day is, you know, kind of classic epidemiology. And he came to the realization that something was going on in utero, that was actually changing these fetuses physiology, that was ultimately leading to the ultimate development of chronic disease, cardiovascular disease, type two diabetes, etc. And he presented that and people started, you know, looking at this question, and they found, you know, similar stories elsewhere, and they started doing animal experiments. And sure enough, it looked like, what the mother was exposed to, ultimately is visited upon the baby, later on. Now, we had always thought that the placenta was this great barrier that kept the mother from the baby. And we had lots of reasons to think that because after all, you know, mom's immune system does not become the baby's immune system. And, you know, we thought that these various transporters that live in the placenta help, you know, determine, you know, the stuff that needs to get in and keep the stuff out that doesn't need to get in. And there are enzymes in the placenta, that keep, for instance, cortisol from getting to the baby. You know, unless, of course, the mother takes something that the enzyme can't work on, like, for instance, dexamethasone, and then it does go to the baby. So we had this notion that the placenta was all seeing and all knowing, and the ultimate, you know, suit of armor for for the baby. And that mother's diet didn't matter, and that mother's medicines didn't matter. And ultimately, when we learned about microbiome, that mother's microbiome didn't matter. That turns out all of that is hogwash. The placenta is not that great. It's, it'll let a lot of stuff across, and it doesn't do what we think it does. And so in fact, the fetus ends up swimming in the same cesspool of contaminants and environmental exposures that the rest of us do. And so it shouldn't be too surprising that those contaminants when they have effects on us, that they would also have effects on the fetus. Now, one of those that I happen to be particularly interested in so I've done a lot of work on obesity, are these chemicals which we now term obesogens. That is, they are chemicals that drive adiposity drive, weight gain, drive chronic disease in humans, both, you know, adults, and as it turns out, also fetuses having nothing to do with their potential inherent calories. So there are a lot of substances that have calories, but generate more adiposity than their calories like my favorite fructose. And there are plenty of chemicals that generate adiposity having nothing to do with calories, like for instance, polyflor alkylated substances pee fast like Teflon, okay, or BPA, Bisphenol A, which turns out to be an estrogen. And, you know, there's a whole host of compounds satellites plasticizers PBDE, is flame retardants. Parabens are things that are in cosmetics, things that are in vinyl flooring things that are in. Oh, and by the way, air pollution to boot. All right. And so you'd think the placenta would be a great way to keep the fetus

About the Guest: Mark Mattson, PhD is a semi-retired neuroscientist at Johns Hopkins who ran a research lab at the NIH for many years. He wrote the book, "The Intermittent Fasting Revolution."Episode Summary: Nick and Dr. Mattson discuss: intermittent fasting & diet; ketosis & metabolic switching; aging & neurodegenerative disease; exercise, stress, and neuroplasticity; and more.* More M&M content about diet & metabolism.* Support M&M if you find value in this content.* Full audio only version: [Apple Podcasts] [Spotify]* Full video version: [YouTube] [Rumble] [Odysee]* Episode transcript below.Full AI-generated transcript below. Beware of typos & mistranslations!Mark Mattson 4:45 When I started reading literature on aging, and there had been Malson rat studies showing that daily caloric restriction, cutting back on calories in extended lifespan of rats When mice, by law if it's initiated when the animals are young, by kind of decreasing increments of its lifespan extension, the later it started in life. And then there were I'd also seen a paper from a group at National Institute on Aging, where I eventually ended up actually, where they showed that every other day food deprivation or every other day fasting, extended lifespan of rats and mice. And so, we had animal models that are relevant to Alzheimer's, Parkinson's, and stroke. And if you're interested and go the details, but anyway, the bottom line, we have models, either their genetic or neurotoxin based or in the case of stroke, it's actually a surgical procedure where you shut up the blood supply trenchantly to the brain. We found if we maintain rats or mice on every other day fasting, we started out by doing three months, and then we found we have to do it a minimum of two weeks to a month. But if we have them on intermittent fasting, and then for example, expose their brains to excitotoxins, in models of Parkinson's, or Huntington's disease, that neurons are resistant to the degenerating and the functional outcome isNick Jikomes 6:32 it's preserved. So being in the fasted state is protective against neurodegeneration.Mark Mattson 6:40 Ah, yes, but we found it can be just a one time fast it, it has to be cumulative over a period of time. And we wait can get to a later but in all of our studies, and other people are finding this too. And it's even true to some extent in human studies that takes two weeks to a month of intermittent fasting to see robust effects on the brain and the heart. And, yeah, so anyway, we can talk about what's happening during those two weeks. Yeah,Nick Jikomes 7:18 well, let's say let's say like, let's just start out with two simple things to orient people here. So first, can you just give us a simple definition of intermittent fasting, and then, you know, let's, let's say that someone starts intermittent fasting today, and they're gonna go for several weeks, let's just say they're gonna go weeks and weeks daily intermittent fasting, walk us through those several weeks in terms of what some of the major physiological changes are going to be?Mark Mattson 7:43 Okay, good. So intermittent fasting, what it snot is a diet and diet is what you eat composition of your diet, and how much intermittent fasting is an eating pattern. And it's any eating pattern that results in frequent, often periodic periods without any foods sufficient to cause a metabolic switch from glucose, to fats and ketones. So in humans, that takes about 12 to 14 hours. If you're not exercising, this kind of normal daily activities. If you exercise a lot of people do this actually say you get up in the morning, after having not needing anything right now before and you go out the door and go on a run for an hour at some time during that run. So during the night, when you're sleeping, you'll be systems using glucose. And when you go on the run, initially, you'll be using glucose because you've only been fasting, say eight or eight to 10 hours. And then at some point in Iran, you're gonna it's gonna start switching the ketones and that are derived from the fats. Actually, I was kind of a amateur an endurance athlete. And this is kind of my explanation of some people, endurance events, they'll be they'll start to race. And they'll be feeling pretty good. And then there'll be some time period where there's like, a decrement in their performance. And then they'll get they'll get their second wind. So of course, I don't think it's a second one. I think it has to do with energy metabolism. So if you if you start the event, in not in a ketogenic state, and then you you're during the time you're switching from glucose to ketones. That takes time it doesn't happen like one second. Your cells are using glucose next year using ketones. There's got to be signaling that the The system essentially the liver, senses, depletion of glucose. And then fat released fatty acids into the blood. And that go into the liver converted to ketones. So that takes many, many minutes. 10s of m

About the Guests: Sean B. Carroll, PhD is an evolutionary developmental biologist at the University of Maryland, who recently stepped down as VP of Education at the Howard Hughes Medical Institute. He is the author of many popular science books, such as "Endless Forms Most Beautiful."Episode Summary: Nick and Dr. Carroll discuss developmental biology & genetics; evolutionary biology; genetics, genome size & genetic mutation; animal diversity; snake venom; human brain evolution; and more.* More M&M content about evolution.* Support M&M if you find value in this content.* Full audio only version: [Apple Podcasts] [Spotify]* Full video version: [YouTube] [Odysee]* Episode transcript below.Full AI-generated transcript below. Beware of typos & mistranslations!Sean B. Carroll 4:31 double duty there is both VP of science education and head of the studio 13 years as VP six years has had a studio that was incredibly busy and you cannot sustain that for infinity. Yeah. I thought it was time to step back and I had my lab here I was going every Friday to the lab but I thought this is I kind of feel like I'm refilling you know the well now back in science for A few months enjoying reading and joining daily conversations about research in the lab. Now still still have a hand in the film storytelling, but I'm not responsible for the production. So I am i I'm in a good place. Okay, great.Nick Jikomes 5:20 What's How big is the lab now?Unknown Speaker 5:23 Eight people?Nick Jikomes 5:24 Oh, that's that's like, that's a good size, I think. Yeah. Yeah.Sean B. Carroll 5:28 So enough for things to be happening and not so many that I'm overwhelmed and, you know, stretched stretched too thin. So yeah,Nick Jikomes 5:36 what? Well, just for background, for people who don't know you, what do you study generally? And then can you just give give us a snapshot of some of the projects you're working on right now?Sean B. Carroll 5:46 Yeah, the central question that's guided thinks for a long time is the origin of novelty, where new things come from, in the course of evolution. And that's really things that are sort of qualitatively novel that either it's body parts that do something new, or molecules that do something new, or give some sort of capability to an organism didn't have before. And I've decided to focus a lot of energy on the origin of steak Venom's and their toxins. Because the fundamental reason why that's interesting venom is had been invented multiple times in the animal kingdom, you know, spiders and scorpions and octopi, and snakes and all that kind of stuff. We've come up with Venom's independently many times. And the question is, where did those things come from are those sort of normal body proteins that you've sort of hijacked to do something new, or you really have this evolutionary stage something together that didn't exist before. And in snakes in particular, there's lots of just the history of snakes, which is under appreciated, how they've sort of invaded continents, brother relatively recently, in evolutionary terms, and flourished, radiated and all sorts of species. They're, they're really under appreciated as models of evolution.Nick Jikomes 7:07 And, you know, one of the things I want to talk about first with you is, you study evolution, obviously, we're going to talk about a lot of evolution stuff, I can remember being, you know, 17, high school student, and I knew what evolution was in the abstract, you know, at the level that you learn about in high school biology, I know that I knew at the time, you know, millions and millions of years go by the DNA mutates, known things emerge. But it was all kind of abstract. And it wasn't until I read your book, endless forms most beautiful, that things kind of collected became much more concrete and just easy to intuit. And I think the reason for that is just, if you are trying to understand evolution, it makes it a lot easier if you first understand something about how bodies are built in development. And then you realize, oh, if I just sort of tweak this process, you know, it just makes everything a lot more blockable, I think to the mind. Yeah, soSean B. Carroll 8:05 we can all appreciate we all develop from an egg, right to single celled egg made all these body parts. So, you know, changes in anatomy, or due to changes in development, and you can appreciate with all these different processes going on, you know, a little tweak, here, a little tweak there can can make a pretty big difference. And, you know, we had no access to understanding those tweaks, you know, really until the 1980s. So that this interested biologists for a really long time, but we couldn't make it concrete until the 80s and 90s. And, and really get into to the the actual mechanism of how bodies are built and how they change. And that, that I think that changed a lot of things for the way we could talk about evolution. Evolution has, you know, evolutionary science has a big theoretical history,

About the Guests: Dr. David Nichols is a retired chemist and father of Dr. Charles Nichols, a researcher studying psychedelics at Louisiana State University.Episode Summary: Nick and David & Charles Nichols, PhD talk about: the history of psychedelics science from the 1970s to the present; DMT & 5-MeO-DMT; serotonin, inflammation, and psychedelics & anti-inflammatory drugs; psilocybin, ketamine, and other psychoactive drugs; and more.* More M&M content about psychedelics.* Support M&M if you find value in this content.* Full audio only version: [Apple Podcasts] [Spotify]* Full video version: [YouTube] [Rumble] [Odysee]* Episode transcript below.Full AI-generated transcript below. Beware of typos & mistranslations!David Nichols 4:46 So when I went to graduate school in 1969, my PhD project was on what are called psychotic mimetics which are now called psychedelics. I was lucky I had an NDA fellowship to Studying, I spent, actually finished my PhD and about actually the experimental work about three, three and a half years faster than most people did. Because I had worked in industry for five and a half years before that. So graduate school for me was like a vacation that people wouldn't think that going from undergrad to graduate school like, Oh, my God graduate school. But I had worked five and a half years in industry and gone to night school to finish my BSN night at the same time. So I was burning the candle on both ends, but the graduate school and the research for me was like a vacation. And so in 1970, the Controlled Substances Act was passed that that well, I'm not going to be able to do this anymore, but at least I enjoyed my PhD work. But then I went to Purdue University in 1974. And got an appointment there and was able to continue doing work on these compounds, actually got a grant from the National Institute of Drug Abuse, which I was funded for 28 years and renewed for the final year 29th year, just studying the medicinal chemistry and pharmacology of psychedelics, basically, that was, I have another area but this that's the one that's most memorable for me, and published a lot of papers, wrote book chapters, reviews, all the academic stuff, trained at 40, some graduate students and 20, some postdoctoral fellows and visiting scholars, and started to have to research institute in 1993, because nobody was doing clinical work on psychedelics. And so I got together with some like minded friends, and we started to have to institute raise money from philanthropist was quite difficult because once you have a lot of money, apparently you'd like to hold on to it, you know, give it away very easily. We did raise about $10 million. And the halftracks had funded the seminal studies really, that really got people looking at psychedelics again. We funded Charlie Grover UCLA we funded to Johns Hopkins studies with Roland Griffith, we fund Steve Ross at New York University. And that really, I think those papers were the the impetus for people to realize you actually could do this work again, because prior to that time, no one got in the field because you couldn't get a grant, and still almost impossible to get a grant to study these substances. So though, a couple of grants have been awarded Now recently, but you couldn't get money to fund these for years. And if you're an academic, without a grant, then you'd lose your job after five years if you couldn't get a grant. So I was in the right place at the right time, worked my ass off and was lucky, got a lot of luck, and was able to kind of push this field forward. I made the MDMA for four maps phase one to two studies. The DMT for Rick Strassman study made the psilocybin for the Johns Hopkins studies. So I was encouraging people to work in this field. Pretty much before almost anybody else was in proving that it could be done.Nick Jikomes 7:50 Yeah, so you've truly been the man behind the curtain. You actually made the MDMA for Rick Doblin map studies and the other ones that you mentioned. Yeah,David Nichols 7:59 yeah. Nobody else would do it. And Rick Doblin had gotten it this eighth set of maps, and he was an ideal, idealistic young kid. I met him when he was still an undergrad at New College. And he wanted to make MDMA into a drug because he'd been so impressed by its effects. And then he started checking with companies to make it for you need to get preclinical toxicology done, he needed some pure material, and nobody would touch it, because it was, you know, they would touch it, but not for the kind of money he had. And so I did that. And then then it was easy to make the DMT for Rick Strassman. And I got FDA, we got FDA approval to do that. And in this psilocybin I started doing synthetic psilocybin. The first batch was used for Hopkins 2006 studies and normal volunteers. And then I made a great big batch for the clinical studies. So that's, and then I retired from Purdue in 2012. At Purdue, I was eventually Distinguished Professor of medicinal chemistry

About the Guest: Dr. Chris Knobbe is a physician (ophthalmologist), diet & nutrition researchers, and author of, "The Ancestral Diet Revolution."Episode Summary: Nick and Chris Knobbe, MD discuss seed oils & their health consequences; different types of seed oils (soybean, corn, sunflower, etc.); omega-6 fats like linoleic acid; fatty acid metabolism and oxidation; obesity, diabetes & metabolic health; processed foods vs. whole foods; mitochondria & oxidative stress; and more.* See this article for more information, including data from some of Dr. Knobbe's lectures.* Other M&M content about diet & metabolism.* Support M&M if you find value in this content.* Full audio only version: [Apple Podcasts] [Spotify]* Full video version: [YouTube] [Rumble] [Odysee]* Episode transcript below.Full AI-generated transcript below. Beware of typos & mistranslations!Chris Knobbe 4:54 Yeah, sure. Next, so I'm a traditionally trained Physician and ophthalmologist, and I really got into this out of my own suffering started with arthritis way back, oh, 30 years ago. And that eventually led me about 1213 years ago to to investigate that, and try not to go into too much detail here. But so I really, I guess the, my arthritis led me to Loren Cordain's book The Paleo answer. And from that, I determined that basically processed foods, refined flour, sugars and vegetable oils, were driving most all of the chronic diseases. And, and so, but there were things about Canadians work that I didn't really agree with didn't understand. And I just kept researching. And eventually, a couple of years later, I came across the work of Weston Price. And really began to connect the dots between processed foods and, and chronic disease in a deeper way that made more sense to me. And that year neck, then I hypothesize that processed foods and vegetable oils, sugars, refined flours, all that might be driving age related macular degeneration, I'm an ophthalmologist at age related macular degeneration, or AMD is the leading cause of irreversible vision loss and blindness and people over the age of 50 worldwide. So I spent about a year and a half, or maybe almost two years investigating that while I was still in practice. And in February of 2015, I was so convinced that that hypothesis held water that I left practice and pursued that full time. Um, so that took about another year and a half of of investigation basically, from that we, you know, we, we looked at data of processed food consumption tracking, proxy markers were processed food in the form of sugars and vegetable oils, and the data and 25 nations supported that hypothesis. So I went public with that, in 2016, published a paper published a book started a nonprofit foundation, and but eventually, you know, the, I kept researching all of this. And the one thing that kept occurring was that in my research was that it was the highly polyunsaturated vegetable oils that seem to be the major drivers of almost of overweight and obesity, chronic disease. And by chronic disease, I mean, diseases like coronary heart disease, stroke, cancer, diabetes, metabolic syndrome, Alzheimer's, dementia, autoimmune disorders, the list goes on. And so I went public with that in 2019. And this is kind of where my, where I've been spending the majority of my time over the last five years or six years really is is, is processed foods and vegetable oils in chronic and chronic disease and overweight, obesity and chronic disease. So that's, that's basically my story now. AndNick Jikomes 8:46 so, you know, when we think about chronic disease, all of the diseases of modern civilization, the things that we're commonly sick with today, that our hunter gatherer ancestors were almost never sick with things like obesity, diabetes, different inflammation driven conditions, you know, all the things that you mentioned, most people in my perception, most people agree that our diet is a big factor in this, and that what's wrong with the diet has something to do with processed foods, whatever exactly those are. But, you know, I want you to get into sort of your explanation for this. Can you start off by just unpacking this graph here and defining very clearly two terms, at least one is What are ultra processed foods? Exactly? In your view? And what are seed oils?Chris Knobbe 9:34 Oh, okay. And I didn't realize I guess we have the graph up there. Yeah, yeah. Yeah. Okay. I meant to stop sharing that and come back to sharing it. Sorry about that. But um, so, so processed foods really, first of all, are made up of four basic things and it's refined flours, refined sugars, vegetable oils, and trans fats and they're saw the you know, so called mystery ingredients to kind of, you know, the, the ingredients that the Met the food scientists concoct in order to give flavors and such.Nick Jikomes 10:14 So that would be like artificial sweeteners and colorings and yes, yeah, allChris Knobbe 10:18 those kinds of things. But if you, but you know, I

About the Guest: Dr. Orrin Devinsky is a neurologist and Professor at the New York University School of Medicine.Episode Summary: Nick and Orrin Devinsky, MD discuss: dietary consumption trends in the US; processed vs. whole foods; vegetable oils & polyunsaturated fats; relationship between saturated fat, dietary cholesterol & heart disease; history of medicine in the US; obesity & diabetes; sugars, fructose, and metabolic health; ketogenic diet & ketosis; whether or not we can trust our public health institutions; and more.* Read this written content to learn more about topics discussed on the podcast.* See this content to learn more about diet & metabolism.* Support M&M if you find value in this content.* Full audio only version: [Apple Podcasts] [Spotify]* Full video version: [YouTube] [Rumble] [Odysee]* Episode transcript below.Full AI-generated transcript below. Beware of typos & mistranslations!Orrin Devinsky 5:11 Yes, I'm a neurologist, I went to medical school, and then did training in neurology, and then subsequently subspecialty training in epilepsy. And I have directed the NYU Epilepsy Center for the past three decades or so. But I have a fair number of other interests from evolutionary biology to nutrition, which I think we'll be discussing here to the history of science, and many of them come together on this topic.Nick Jikomes 5:35 Yeah, you.We're gonna talk basically about one paper today and some related topics, but you have this paper come out not so long ago, called United States dietary trends since 1800. Subtitle is lack of association between saturated fatty acid consumption and non communicable communicable diseases. So, you know, very briefly, your neurologist, you've got all these other interests, but what actually got you to write a paper about this particular subject.Orrin Devinsky 6:09 So it's interesting, I think, going back 12 or more years ago, I took a family vacation in Mexico. And a good friend of mine bought me a book by Gary Taubes called good calories, bad calories. It was a big paperback. And having lots of time on a chair on the ocean, I read it cover to cover and it kind of blew my mind. It just completely shocked me that I was reading about parts of history that I just assumed were black and white, factual that we're not and things I was taught in medical school, my medical training and career had been wrong. And actually, we read the book during that vacation and since then, have become friends with Gary. And that led me to a deep dive into nutrition and health. Yeah, I mean,Nick Jikomes 6:58 in a vague way, you know, I've had, you know, somewhat of a similar experience. So, you know, my background, you know, my PhD is in neuroscience, but I actually worked in the department of diabetes, endocrinology and metabolism at the Beth, Beth Israel, Deaconess Medical Center in Boston. So you know, I spent a lot of time thinking about feeding and metabolism and stuff like that. But I had sort of no knowledge of the history of the dietary recommendations and how all of the things that I thought were just the cold, hard facts of medical nutrition that I grew up with, and that I was taught, you know, as I grew up, about what to eat, what not to eat, I had no idea what the history actually was. And we're gonna get into some of that. Just to sort of start to set the stage for some, folks, before we get into the trends of the things you analyze in this paper. I want to talk about a few different things, and put put some historical context here for people. So roughly speaking, when we think about things like the obesity epidemic, the rise and diabetes, roughly when did these things start to clearly rise in the United States? SoOrrin Devinsky 8:05 I would say Eliot Joslin, who founded the Harvard Diabetes Center, where you worked was America's preeminent diabetologist, at the turn of the 20th century, going from the late 1800s, into the early 1900s. And he actually observed an epidemic, as he referred to it, of diabetes in his little hometown of Oxford, Massachusetts, where all of a sudden, many people were developing adult onset. So it was called at the time diabetes. So I think the these have been slowly creeping, but exponential epidemics of obesity and diabetes, probably going back centuries. I think it began in the wealthy class of people. So if you go back to the Middle Ages, and you look at who, you know, the fat, the fat was a not uncommon eponym after King so and so the fat and the only people who could be fat in the Middle Ages, were royalty, because they were the only ones who could afford the processed foods that could make you fat. SoNick Jikomes 9:10 it was an eponym was actually probably a marker of status because it was so hard to actually doOrrin Devinsky 9:17 that. And I think people didn't even understand obesity. There's one terribly racist but informative line from a doctor you trail he was one of the English what they called colonial physicians in the 20th centu

Dr. Artemis Simopoulos is a physician and researcher specializing in endocrinology, nutrition, and metabolic health. They discuss: traditional hunter-gatherer diets vs. modern Western diets; dietary fats; omega-6 and omega-3 polyunsaturated fats; sucrose & sugar; chronic inflammatory diseases, obesity & diabetes; vegetable & seed oils vs. other cooking oils; processed foods; fish oil supplements; and more.* See this content to learn more about diet & metabolism.* If you enjoy my content and want to further support M&M, please read this. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit mindandmatter.substack.com/subscribe

Dr. Carolina Tropini is an assistant professor of Microbiology & Immunology at the University of British Columbia, where her lab studies the microbiome in health & disease. Topics covered: infant & vaginal microbiome, breast milk nutrients & C-sections vs. natural births; oral microbiome & cavities; gut microbiome & irritable bowel disease (IBD); fiber, short-chain fatty acids & probiotics; how gut bacteria influence sex hormones (estrogen, testosterone) in the body; and more.* Click here to download audio, watch video, or read show notes & transcripts. * See this content to learn more about diet & metabolism* If you enjoy my content and want to further support M&M, please read this. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit mindandmatter.substack.com/subscribe

Dr. John Speakman is a biologist whose research focuses on energy balance, energy expenditure, genetic and environmental drivers of obesity and the energetic contribution to aging. They discuss: the history of the obesity epidemic in the US vs. China; changes in patterns of physical activity, diet, and energy expenditure in humans over time; how saturated fats vs. PUFAs affect basal metabolism; the relative contributions of fats, carbs, and protein to fat & weight gain; and more.* Click here to download audio, watch video, or read show notes & transcripts. * See this content to learn more about diet & metabolism* If you enjoy my content and want to further support M&M, please read this. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit mindandmatter.substack.com/subscribe

Dr. Ronald Krauss is a physician and researcher at UCSF who studies the relationship between diet & cardiometabolic health. They discuss: saturated vs. unsaturated fats; carbohydrates & fat synthesis; "good" vs. "bad" cholesterol; official US dietary guidelines and how they're established; funding of research by the food industry; and more. * Click here to download audio, watch video, or read show notes & transcripts. * If you enjoy my content and want to further support M&M, please read this. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit mindandmatter.substack.com/subscribe

Dr. Tobias Egner is a Professor of Psychology & Neuroscience at Duke University, where his lab studies cognition, working memory, and cognitive control & flexibility. They discuss: what cognition is and how it's studied experimentally; working memory & attention; cognitive flexibility, cognitive control & multitasking; memory, perception, and predictive coding; and more.* Click here to download audio, watch video, or read show notes & transcripts. * If you enjoy my content and want to further support M&M, please read this. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit mindandmatter.substack.com/subscribe

Dr. David Puts is a biological anthropologist at the Penn State University. His research focuses on the evolution and development of human sexuality and sex differences. We are especially interested in how sex hormones influence our sexual psychology, behavior, and anatomy—and how these traits were shaped by sexual selection. They discuss: the biological basis of sex; gametes, sex chromosomes & sex hormones; the development of sexual orientation; the evolution of sexual dimorphism & behavior in primates; monogamy & polygyny; and more.* Click here to download audio, watch video, or read show notes & transcripts. * If you enjoy my content and want to further support M&M, please read this. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit mindandmatter.substack.com/subscribe

Dr. Moses Chao is a professor at the New York University School of Medicine. His lab studies how the environment, neuronal activity, inflammation, injury and disease affect the nervous system. They discuss topics related to his new book, "Peripheral: How Your Nervous System Predicts and Protects Against Disease." Topics include: how the peripheral nervous system differs from the central nervous system; the enteric nervous system & gut health; pain sensation; exercise & neuroplasticity; neurodegenerative disease; and more.* Click here to download audio, watch video, or read show notes & transcripts. * If you enjoy my content and want to further support M&M, please read this. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit mindandmatter.substack.com/subscribe

Mikael Palner, PhD is a neuroscientist at the University of Souther Denmark. His lab studies the neuronal circuits involved in obsessive compulsive disorder and anxiety . They investigate the effects of serotonergic psychedelic and non-psychedelic drugs that increase neuronal plasticity. They discuss: psychedelics & the brain; the neuroscience of stress, anxiety & compulsive behavior; microdosing psilocybin; and more.* Click here to download audio, watch video, or read show notes & transcripts. * If you enjoy my content and want to further support M&M, please read this. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit mindandmatter.substack.com/subscribe

Dr. John Hawks is a paleoanthropologist and professor of anthropology at the University of Wisconsin-Madison. They discuss: the evolution of human behavior, diet, anatomy, and culture; Neanderthals, Denisovans, Homo erectus, and other species; the latest discoveries related to Homo naledi, which was the subject of the Netflix documentary, "Cave of Bones."* Click here to download audio, watch video, or read show notes & transcripts. * If you enjoy my content and want to further support M&M, please read this. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit mindandmatter.substack.com/subscribe

Dr. Mario Capecchi is a professor of genetics at the University of Utah & Nobel laureate. He discussed: his latest work in neurobiology, looking at the role of microglia in anxiety & Obsessive Compulsive Disorder (OCD); his Nobel Prize-winning work in molecular genetics; molecular biology & genetics; his childhood experiences as an orphan in Italy during World War II; immigrating to the US; his education & scientific career; his exercise & diet; advice for aspiring scientists; and more.* Click here to download audio, watch video, or read show notes & transcripts. * If you enjoy my content and want to further support M&M, please read this. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit mindandmatter.substack.com/subscribe

Dr. Adriene Beltz is an associated professor of psychology at the University of Michigan who studies the effects of sex hormones & hormonal contraception on human cognition and the brain. They discuss: sex hormones (androgens & estrogens); hormonal regulation of menstruation, puberty, and pregnancy; common forms of hormonal birth control & how they work; effects of sex hormones & hormonal birth control on cognition & the brain; and more.* Click here to download audio, watch video, or read show notes & transcripts. * If you enjoy my content and want to further support M&M, please read this. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit mindandmatter.substack.com/subscribe

Nick talks to Dr. Matthew Hill, a neuroscientist at the University of Calgary whose lab studies how the endocannabinoid system and cannabis (marijuana) influence the brain & behavior. They discuss: endocannabinoid biology; endocannabinoid regulation of stress & anxiety; endocannabinoids & exercise; how marijuana & THC influence brain development; and more.* Click here to download audio, watch video, or read show notes & transcripts. * Previous episode with Dr. Matthew Hill: “Endocannabinoid System, Stress & PTSD”* If you enjoy my content and want to further support M&M, please read this. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit mindandmatter.substack.com/subscribe

Nick talks to molecular physiologist Dr. Vijay Yadav, an assistant professor at Columbia University whose lab studies the molecular & cell biology of aging, nutrition, and longevity. They discuss: the cell biology of aging; how nutrients affect aging & disease; the atypical amino acid taurine & its effects on aging; taurine clinical trials & supplementation; diet, nutrition & anti-aging effects; and more.* Click here to download audio, watch video, or read show notes & transcripts. * If you enjoy my content and want to further support M&M, please read this. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit mindandmatter.substack.com/subscribe

Nick talks to Gül Dölen, MD, PhD., a neuroscientist at Johns Hopkins University whose lab studies social behavior, synaptic plasticity, psychedelics & evolution. They discuss: What drugs like LSD, psilocybin, ketamine, MDMA, and ibogaine have in common in terms of their molecular effects in the brain; why Dr. Gül Dölen believes all of these drugs can be described as "psychedelics"; the relationship between psychedelics and neuroplasticity vs. metaplasticity; how addictive drugs are similar to and different from psychedelics; social reward learning in rodents & critical periods of plasticity; the subjective effects of psychedelics; novel psychedelic drug development; human social behavior, mental health, and psychiatry; and more.* Click here to download audio, watch video, or read show notes & transcripts. * If you enjoy my content and want to further support M&M, please read this.* Check out my previous discussion with Gül Dölen for important background information. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit mindandmatter.substack.com/subscribe

Nick talks to Dr. Alan Davis, a clinical psychologist and Director of the Center for Psychedelic Drug Research & Education at Ohio State University. They discuss: the effectiveness of mainstream forms of psychotherapy and antidepressant medications (SSRIs) for depression; psychedelic medicine & psilocybin-assisted psychotherapy; the relevance of the subjective effects of psychedelics for their therapeutic effects; FDA approval for MDMA- and psilocybin-assisted psychotherapy in the coming years; and more.* Click here to download audio, watch video, or read show notes & transcripts. * If you enjoy my content and want to further support M&M, please read this. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit mindandmatter.substack.com/subscribe

Nick talks to Bryan Roth, MD, PhD, a Professor of Pharmacology at the University of North Carolina. Dr. Roth has been studying the molecular mechanisms of psychedelics since the 1980s. They discuss: serotonin 2A receptors in the mammalian brain; psychedelics & neuroplasticity; classic psychedelics (e.g. LSD, psilocybin, DMT) compared to drugs like ketamine & MDMA; TrkB receptors & BDNF; engineering novel drugs & psychiatric treatment methods; latest findings in psychedelic science.* Click here to download audio, watch video, or read show notes & transcripts. * Dr. Roth’s first appearance on the podcast: M&M #4 | Drugs, Receptors, Zen Meditation & Psychedelics.* If you enjoy my content and want to further support M&M, please read this. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit mindandmatter.substack.com/subscribe

Nick talks to ethnopharmacologist Dr. Dennis McKenna, who is the brother of psychonaut Terence McKenna and author of the book, "The Brotherhood of the Screaming Abyss." They discuss: the lives and psychedelic adventures of Dennis & Terence McKenna; experiences with psilocybin mushrooms & DMT; Carl Jung & psychology; the medical relevance of subjective psychedelic experiences; drugs, culture & society; and more.* Click here to download audio, watch video, or read show notes & transcripts. * If you enjoy my content and want to further support M&M, please read this. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit mindandmatter.substack.com/subscribe

Nick talks to Daniel Karlin, MD, a board-certified physician in psychiatry, addiction medicine & clinical informatics who is the Chief Medical Officer at MindMed. They discuss: psychiatry; incentives in scientific & medical research; healthcare & mental health; psychedelics; LSD for anxiety; MDMA for autism; ibogaine derivatives for addiction; patient access & care; and more.* To access the full version of this episode, become a paid subscriber.* Click here to download audio, watch video, or read show notes & transcripts. * If you enjoy my content and want to further support M&M, please read this. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit mindandmatter.substack.com/subscribe

This is a free preview of a paid episode. To hear more, visit mindandmatter.substack.comNick talks to Daniel Karlin, MD, a board-certified physician in psychiatry, addiction medicine & clinical informatics who is the Chief Medical Officer at MindMed. They discuss: psychiatry; incentives in scientific & medical research; healthcare & mental health; psychedelics; LSD for anxiety; MDMA for autism; ibogaine derivatives for addiction; patient a…

Nick talks to chemist & food scientist Dr. Selina Wang about: food quality & purity; cooking oils (avocado, olive, vegetable, etc.); fruits & vegetables; oxidation & purity of cooking oils; how to identify high quality, pure foods to purchase; and more.* Click here to download audio, watch video, or read show notes & transcripts. * If you enjoy my content and want to further support M&M, please read this.Timestamps:0:00:26 Intro0:06:11 What is Food Quality?0:15:51 Health Effects of Oxidized Oils0:22:08 Different Types of Olive Oil0:30:29 Refined Oils0:40:27 Olive Oil Study0:47:28 Best Way to Store Olive Oil0:54:02 Study Results (Quality & Purity)1:00:13 Best Brands1:06:19 Avocado Oil Study1:13:57 Enforcement of Standards This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit mindandmatter.substack.com/subscribe

Nick talks to Dr. Luc van Loon, Professor of Exercise Physiology & Nutrition at Maastricht University, about topics in exercise science, health & nutrition. They discuss: macronutrients & energy; protein quality & digestibility; endurance & resistance training; plant vs. animal protein; muscle conditioning & muscle fibers; sleep & aging; muscle physiology & metabolism; and more.* Click here to download audio, watch video, or read show notes & transcripts. * If you enjoy my content and want to further support M&M, please read this.Full AI-generated transcript (beware of typos!):Luc van Loon 6:34 Yeah, so what I have a chair in physiology of exercise and nutrition. My basically supervise a group of researchers but 30 people here at Maastricht University Medical Center, the study basically the interaction between physical activity and exercise and nutrition. And we do this in an attempt to improve performance, for example, in athletes, but all the way down to basically the impact of lack of physical activity and lack of sufficient nutrition in intensive care unit patients and everything in between. So anywhere where we can actually affect the interplay between nutrition and exercise.Nick Jikomes 7:19 And normally when we talk about nutrition, you know, one of the big things people talk about are the major macronutrients, fats, carbohydrates, proteins, can you give people just a very basic overview of what those things are and how the body utilizes each type of macronutrient for energy.Luc van Loon 7:40 Yeah, so it's interesting from my career basically started with the interaction between carbohydrate and fat metabolism. And my lab now mainly revolves around protein metabolism. So I have experienced some of the work in the different fields. So you have three basic macronutrients, carbohydrates, fats, and protein. The carbohydrates and the fats are basically substrates for energy provisions. So fuels basically, there's one big difference between the fuels, carbohydrates and fats, fat basically gives you a lot of energy per gram, almost twice as much as carbohydrates. And with fats, you can actually perform lower intensity exercise for a prolonged time duration. And that's a nice thing. And it also makes it very efficient fuel source, because you can actually store a lot of energy in the form of fat. That's why most of our energy stored in our body is stored as fat because if we would store it as carbohydrates, we will basically become twice as heavy. But the carbohydrates are an important fuel source, because you can actually sustain high intensity exercise with a carbohydrate oxidation. And that is because with high intensity exercise, it's easier to get the energy that is actually inside the carbohydrate to get them out faster. So in people that don't have a nutritional or biological background, I always explain it that fat is like diesel. And carbohydrates are like kerosene. So your body always uses a combination of the two, to mix and match in order to have the optimal performance. And that's also one of the reasons why you always hear about athletes taking carbohydrate drinks and stuff like that, because your total storage of carbohydrates is much smaller than fat. And that's why in some cases, carbohydrate supplementation helps people perform optimally during higher intensity exercise over a more prolonged period of time. Let's ensure it in a nutshell the basics of carbohydrates and fat and these indirect Of course, protein can be used as a substrate for energy provision, but it's it's not very efficient on that and the body doesn't really do it. Protein is basically a micronutrients that is composed of long strands of amino acids, the building blocks of proteins. And these amino acids are being used by the body to build proteins. And basically, you are composed of proteins. So your muscle, but also part of your bone and your organs. It's all made of proteins. And so we need protein in order to maintain our tissues, both health and integrity.Nick Jikomes 10:26 And, you know, in terms of fats, their saturated and unsaturated fats, is there a difference between them in terms of, you know, how much ATP can be used, can be made, if you have one type versus the other, whether or not one is sort of better for giving you energy for exercise or anything like that.Luc van Loon 10:46 Yeah, I mean, for for, for fats, it's all depends on of course, the size of the chain, you will have short chain fatty acids, you have long chain fatty acid, yes, prize. So let's roll so, so you have all kinds of fats. So that all differs between the different fats. And it's not necessarily a discussion about saturated or unsaturated fatty acids, that has much more to do with, of course, health benefits of that, and it's far beyond my level of expertise.Nick Jikomes 11:18 Got it. And then in terms of, you know, Protein Protein is used, it can be used for energy, but it's primarily used, you know, to make to make the proteins of the bod

* Click here to download audio, watch video, or read show notes & transcripts. * If you enjoy my content and want to further support M&M, please read this. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit mindandmatter.substack.com/subscribe

This is a free preview of a paid episode. To hear more, visit mindandmatter.substack.comNick talks to Dr. Iain Oswald, who has a PhD in chemistry from the University of Texas-Dallas and is principal scientist Abstrax Tech, a cannabis research and product development company. He is an expert in using cutting edge analytical chemistry techniques to study plant chemistry and has done a lot of work to decipher the chemistry of commercial canna…

Nick talks to board-certified toxicologist Dr. Echo Rufer. The conversation starts with a brief overview of what the science of toxicology is all about & a little bit about alcohol toxicity. They then discuss: differences between vaping and smoking; what toxins are produced through the combustion of plant material, especially tobacco & marijuana; cannabinoids like THC & CBD, as well as cannabis terpenes; relationship between dose, method of consumption & toxicity of chemical compounds; causes of the vaping-associated pulmonary injury (VAPI) associated with the vitamin E acetate that was found in some illicit market cannabis vape products; best ways to minimize toxin exposure for people who inhale plant-based consumer products such as tobacco or nicotine products or marijuana. * Click here to download audio, watch video, or read show notes & transcripts.* If you enjoy my content and want to further support M&M, please read this. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit mindandmatter.substack.com/subscribe