 This is, that means a lot to me to hear that. I feel like I was stuck off in the hinterlands of Alabama talking about evolutionary mismatch and all this stuff. And everybody looked at me like I was from Mars. And I just, so going to that meeting with you guys was when I finally felt like I'd found my group. So yeah, this talk is entitled evolutionary mismatch is a meta theory for chronic disease states. This is what sort of the outline of the talk is going to be. Like just answer like, what is evolutionary mismatch in general? Like just a very generic sort of understanding of what it is. And then I'll talk about how mismatch fits into the larger framework of what has been called Darwinian medicine or evolutionary medicine. And this will include sort of a digression on some of the other like mid-level theories of disease and dysfunction. And then I'll talk about what might be called Tim Bergen's legacy, Nico Tim Bergen's legacy in ancestral health. Particularly when it comes to something called supernormal stimuli and evolutionary traps. And then I'll talk about something that I've come up with this term mismatch blindness for lack of a better term. Perhaps there's another word for it out there but I can't find it. We'll talk about mismatch blindness. And then we'll talk about like overcoming this mismatch blindness to recognize and mitigate the effects of mismatch. And then like using this paradigm or this framework to extend human performance in other novel environments. And then finally I'll summarize by arguing that like mismatch can be thought of as a kind of meta theory for chronic age related disease. I'll give some parallels with how the development of the germ theory might give us clues about how we might be as successful at treating chronic diseases the same way that the germ theory helped us like essentially crush infectious diseases. So some of you may have seen this from the onion a couple of years ago. I spread it on my Facebook page every year or two just because it's funny. The title there is, the idiot zoo animal with zero predators still protective of her young. And then it says, dimwittedly refusing to let her offspring venture more than a few feet away from her and idiot gazelle at the San Diego Zoo was reportedly still protective of her young Tuesday despite facing absolutely no predators. The closest actual threat is thousands of miles away but this dummy honestly thinks that she has to guard her babies. What a stupid moron, right? Kind of a comical example there. So what is evolutionary mismatch? Well, very simply and most of you this is all kind of well established here among you guys but for the listening audience some of this may be new. An evolutionary mismatch occurs when an adaptation or set of adaptations having evolved in response to statistically recurrent to a statistically recurrent problem in the ancestral environment fails to operate properly in the modern environment or the contemporary environment. Or it can also be thought of as like when an adaptive mechanism misfires in the current environment due to evolutionary novel cues or environmental cues. Sometimes it goes by the term time lag or time lag effect or discordance theory. So these are all kind of different but related ways of thinking about it. I first encountered this concept in a very clear way reading Richard Dawkins book probably my favorite Richard Dawkins book it's called The Extended Phenotype. I read it when I was like 20 years old and there was a chapter there called Constraints Upon Perfection. And Dawkins wrote that organisms are perpetually out of date. The present traits of extant organisms are generally forged when environmental conditions were different, okay? And the sort of the paradigmatic example might be thought of as like a moth circling around an artificial light. We've all seen this. We see this every day inside cities or near straight lamps, right? Moths evolve to navigate using light reflected from the moon, which is at optical infinity. So a moth can fly in a straight line with respect to the moon and the moon appears to stay at a fixed location. But boom, a mirror 100 years ago when an incandescent lighting appeared in the environment, you know, now the moths navigational systems get confused and so they swim, they fly around in this perfect like parabolic spiral and they get trapped in these environments. Later around the early 1990s, this young medical doctor named Randolph Nessie teamed up with a brilliant evolutionary biologist named George C. Williams and they published a paper in a quarterly review of biology called The Dawn of Darwinian Medicine. No, I think that was 1991. Later followed up by a general nonfiction book called While We Get Sick. This should be like if we ever offer a course in ancestral health, like an academic course, this should be like the first thing you read is while we get sick, maybe even that original paper too or both. So they said, they asked in that paper, like, okay, if evolution is powerful enough to sculpt complex functioning adaptive systems with what we call organisms, you know, there are more statistically improbable and complex than any human invented machine. How is it then that it's not perfect, that we still suffer from disease and dysfunction? And after a number of years, they realized that there are six broad categories for why evolution, again, is powerful as it is nonetheless left our bodies vulnerable to dysfunction. And I'm just gonna kinda run through these six quickly and we'll talk more about mismatch as you can probably guess later. But one would be like the host parasite co-evolutionary arms race. Pathogens can crank through many more generations during the last spin of one individual. They can reproduce, bacteria can reproduce within like minutes, right? So they have a lot more time to actually evolve ways of outwitting our defense mechanisms. So we're always in this, what's been called the red queen race, like this arms race with these pathogens. Another example would be like trade-offs. Example, there was selection pressure in Homo sapiens to have a large brain starting in utero and fetal development. But that was constrained by, there was a trade-off because the brain couldn't get too big because it would pose dangers during childbirth because the mother's pelvis could only get so big, right? So trade-offs are involved. There also has been what they call design constraints or historical legacies. Like the windpipe opens up into our throat because of how the phylogenetic history is of tetrapods like us. Well, this can lead to a choking hazard now. But there's not much we can do about that really. You know, it's interesting to know that. And also surprisingly, the goal of evolution is not to produce health per se, but it's actually to produce health as long as it's tributary to reproductive success. So example where that may cause medical problems where we might be like dangerous risk-taking among the young, especially in males, right? You know, driving fast, doing all kinds of, I mean, we could give whole lectures about, we could have a whole symposia about male stupidity when it comes to taking risks or just young people in general. And also importantly, defenses, there are things that are not diseases or dysfunctions, but they actually make patients feel bad. These things are actually defenses against other diseases or pathogens. And they include things like coughing, sneezing, fever, depression, anxiety, anger, sadness, morning sickness. Someone asked Dr. Emily Deans this morning about like, well, is there a time when we should maybe not treat depression? And she was like, yeah, there are times when depression is actually appropriate, right? So this is an area where in ancestral health we might in the future think of ways in which mismatch, which is this last category, like intersects with, you know, defenses. We wanna not, we want mismatch to be a broad meta theory, but we don't wanna over-apply it, okay? And we might all think about ways that mismatch could be tilting the playing field away or toward like drug-resistant bacteria. And people are already starting to talk about this and like the microbiome. Well, so of those six reasons, you know, gosh, our understanding that germs exist actually, and they sometimes cause pathology is one of the greatest triumphs in all of scientific history. Like we were able to invent vaccines and antibiotics and drive certain things like smallpox to extinction, you know? These great scourges of humankind have been successfully more or less conquered by this part of medicine. And now failure to understand the evolutionary process though has led to the fact that now we're facing like drug-resistant pathogens. So, you know, this is gonna be like the germ pit theory 2.0 applying evolutionary medicine to that. But as most of you may know, yeah, so the other big area though is of course mismatch, right? And this is probably related to almost the, almost certainly the majority of the chronic illnesses that we face. And so, you know, it's like currently like 50% of the global population now has probably has one or more chronic diseases. That may be an underestimate, right? So I think we might be on a real, a conceptual breakthrough here that could do something like for chronic disease, what the germ theory did for infectious disease. So, going on to Nicko Timbergin's legacy and ancestral health, he argued that like a complete biological explanation of any phenomenon requires an understanding that there are both proximate mechanisms giving rise to a biological phenomenon as well as ultimate explanations. And he broke those into two different types or subcategories of proximate and two subcategories of ultimate. Basically, the current like medical paradigm is mainly focused on the various proximate mechanisms. You know, hyperinsulinemia is leading to down regulation of the insulin receptors or this or that. Signaling pathway is not working right. How can we invent drugs? Do this going to do this thing at the approximate level? So, ancestral health and evolutionary medicine as a whole is trying to say, okay, let's try to round out these proximate explanations with the ultimate ones. So, but Timbergin is less, maybe a little bit less well known for the concept of a supernormal stimulus or supernormal stimuli that can occur when the frequency, duration, or intensity of an environmental cue is increased in a novel environment such that the behavior it elicits is stronger than what have been seen in the ancestral environment or that's sometimes called the EEA, the environment of evolutionary adaptiveness, right? The ancestral environment. So, organisms generally don't have ways to filter out these strong signals and may respond inappropriately in an environment that contains supernormal stimulus or stimuli. We all talk about the presence of hyperpalatable foods in the modern environment. That's, I think it's reasonable to say that those are probably, they flooded the market because they tap into our evolved preferences and so now they're ramped up into like supernormal levels. Pornography, drug addiction, et cetera. Also interestingly, Timbergin described what he called physiological traps and people have talked about these in the literature. They've talked about sensory traps or ecological traps, over position traps, but the more general term is evolutionary trap. And this is, this can occur when in an environment that has been altered suddenly by human activities in which case an organism makes maladaptive behavioral or life history choices based on formerly reliable environmental cues despite the availability of higher quality options, right? So, another good example, some of you may be familiar with this. Sea turtle hatchlings evolved to mostly hatch out of their nest in that time, right? And they, like the moths, would have relied on cues from the moon because if you imagine being a baby, see a sea turtle and you hatch out and you just open your eyes for the first time, where's the only source of light for millions of years would have been blue light reflecting off the ocean surface. That's your first mission is to get off the beach because you can get eaten or gobbled up if you hang out on the beach too long. So it's like critical to its survival. It gets off the beach as soon as possible. And we've all seen cute videos of, you know, a turtle scrambling toward the water. Well, of course, you know, boom, I mean, 100 years ago, artificial lights get put on the beach. So now it screws up their navigational systems. Some other delightful examples I wanna thank George Diggs for bringing some of these to my attention. On the upper left there, there's a frog that has apparently mistaken, you know, an artificial light for a bioluminescence prey item. On the upper right there is a shore bird that has gobbled up a bunch of plastic. There's a lot of attention now toward plastic in the environment, and especially the marine and aquatic environments. All kinds of organisms are just gobbling up these plastic bits, you know, that they're blind, right, to the fact that a little squiggly, smushy looking blue thing is actually not a food item, but it's a piece of plastic, right? And the most delightful of all in this match examples, again, credit goes to George Diggs for bringing this to my attention is the, on the lower left there, the male jewel beetle just happened to happen to be attracted to the, those are billed bear bottles that were manufactured in the 1980s in Australia. And evidently to a male jewel beetle, that's pretty hot stuff there. That the female has, you know, has like a golden carapace, you know, golden dimpled pear case or carapace. So that's like super hot to her. And as Dr. Diggs pointed out, evidently these jewel beetles were congregating on these bear bottles and would stay there until they died of dehydration or ants would come up and bite their ding-dongs off. Is that, that's true, and it's not my fault. And also, but thankfully, thankfully actually there was public awareness about this and the bear bottle, the bear manufacturers changed their design, right? So that's nice. And the last example, a lot of aquatic insects like are attracted to the polarized light that comes off of it. Well, they're naturally supposed to be able to zoom in on aquatic environments where they can lay their eggs, but solar panels and some windows and glass surfaces change a lot such that polarized light is emitted. And then so they're mistaking these solar panels and these glass surfaces and lighting on their attempting to over posit on these surfaces. So an example that I talked about last fall to my students up in Bigampton, New York, one of my favorite examples actually from a 2017 paper just last year from a grief and colleagues, acoustic mirrors as sensory traps for bats. They used the, they didn't experiment with these, with myotis, myotis, the greater mouse-eared bat and they set up this contraption, this experimental chamber where they put, placed a really flat, smooth, middle plate both on the floor of the enclosure and also on the wall of the enclosure, okay? And then they released these bats into this chamber and then they filmed their behavior in this environment with these high-speed cameras. It's good to keep in mind that in the natural world there would have been nothing this smooth, right? So that if you're a bat flying around, almost everything would have reflected sound waves because even a pretty smooth sheer rock face would still have little dimples and things that would reflect back enough light to these bats that use echolocation to navigate through their environment, right? Well, when in the presence of this evolutionary novelty, right, in a very smooth surface, if the bat is flying, and if you see on number two there, right, the bat, if the bat is flying directly into the smooth surface, the sound waves bounce back and it can avoid the glass or the metal surface you know, quite well. But when the angle is more obtuse there, like in scenario one, the light waves, excuse me, the sound waves reflect off an insufficient amount or intensity of the waves reflect back. So let's see what actually happens. If I can get the video to work. The first video is gonna show you what happens when they put the smooth surface along the floor. Here we go. Can you see that? The bats are flying in and they're actually evidently attempting to drink from the surface there, okay? The next thing is gonna show you what they call near collisions. If you look on the left there, it shows you sort of the side view and the bat flies in and it almost hits the, now here it is where there's a collision with a maneuver. So the bat takes evasive action at just the last moment. It's flying in at a more obtuse angle. And finally, and this is everybody's favorite, collision without maneuver. So that's pretty awesome, huh? So I like that example because it shows you the actual proximate mechanisms involved. Like we can talk about mismatch in a general theoretical way but this gets into the nitty-gritty of the actual, what actual proximate mechanisms involved. And you can keep doing studies and figure out exactly what is the angle and how does that, what angle does it increase the probability by x amount? It's a perfect example of like the ultimate and proximate levels of explanation. So of course, people say, okay, well, where these mismatches are occurring, what we live in this modern environment, there's nothing we can do about it, right? Who cares, you know? Well, this is kind of a moot point because as anthropogenic changes brought about by the agricultural revolution, however, with some caveat from what Dr. Rose talked about yesterday regarding what I'm calling the Rose Rutledge effect. But especially after the industrial revolution, these changes were very sudden and comprehensive and numerous, right? And besides, the goal of medicine is to reduce suffering in currently existing individuals. We don't want to just wait around for evolution to help organisms adapt to this new environment because species may go extinct or whatever in that meantime or they're gonna have reduced functionalities, right? Plus as the smartest organisms on the planet, I mean, we shouldn't just run around and be oblivious to these mismatch effects, right? Especially when they're causing damage to ourselves or other species. This photograph, by the way, I'm sorry, I'm looking at the wrong slide here because of this next slide here. You've been looking at that one, right? Excuse me, I apologize about that. So yeah, so at some point, of course, mismatch occurs, you know, mismatches have always been occurring for millions of years. It's synonymous with evolutionary selection pressure and as the critic of the ancestral health movement, Marlene Azook, pointed out in her book, Paleo-Fancies, organisms are constantly out of date, right? They're always facing some degree of change in the environment, right? Temperatures are always changing or they're always faster predators, they've been co-evolving with us or more dangerous parasites. So, you know, why even bother? It's not like evolutionary selection just stops, right? But this gets onto the next slide. I just explained, this is kind of a moot point, right? We want to fix these problems, address them. We don't want to wait around for another 300 generations before hopefully we can reduce this mismatch. These photographs, by the way, are those taken by my grandfather who went on a photo safari in Kenya in 1969. That's of the Acacia environment there. Savannah, I thought those were beautiful. I thought I would include those. So, mismatch blindness. You know, a peculiar feature of mismatch is that we organisms are kind of blind to these evolutionary novel dangers, right? And whereas we have evolved defenses or alert systems to evolutionary familiar dangers, such as dehydration, starvation, predators, disgust mechanisms, we have evolved disgust mechanisms against like disease-laden food. We have that way before we had the germ theory, right? We have these like alert systems that can tell us, you know, hey, you might want to avoid that or go more toward this. We have emotions like guilt, shame, jealousy to alert us to behaviors that might be threatening our social or sexual interest, right? But importantly, we lack and we can be expected to lack adaptations that alert us to dangers of processed food, excessive bright light, at night time, lack of exercise, et cetera. So, the ancestral health strategy is all about recognizing these novel threats and trying to design like a lifestyle around these, right? So, this is where I think, going forward, we need to try to like develop mismatch theory so that we can like anticipate mismatch effects before they occur. An example, and we've had success at this. If you think about it, like when long duration trans-oceanic sailing voyages were taking place, one of the things that started happening is people were getting, the sailors were getting scurvy, right? And I read the other day in preparation for this that in some cases in British military or naval history, scurvy and other diseases were causing more deaths than combat, okay? And then sort of like there was sort of a haphazardly, they discovered that citrus fruit could prevent scurvy. We know though that's because they were suffering from vitamin acute, vitamin D, excuse me, vitamin C deficiencies. Well, you know, they did that without an explicit understanding of mismatch theory. So, going forward, looking at the things that humans are doing now, like scuba, if you think about it, scuba equipment, self-contained underwater breathing apparatus, they could be thought of as kind of a bundle of biohacks, right? There's like a little, self-contained little series of gadgets that are trying to recreate some basic. Evolutionarily familiar things like oxygen and such, right? Those of you who know anything about flying, we big apes have not been flying around in heavier than air flying contraptions very long, less than, barely over a hundred years, right? Well, the instrument panel, we have to have a series of instruments that alert us to how the position of the plane and all that. Well, there's this thing called the artificial horizon, or the attitude indicator. Why is that the attitude indicator, not just a series of dials, black and white numbers and dials like the other instrument? I was talking to Tess this morning, she's been learning how to fly. You know, well, the artificial horizon tells you is the plane flying toward the ground or not? Why does it simulate the brown of the ground and the blue of the sky? Because it taps into our evolved ability to recognize horizon from sky, right? It's more evolutionarily familiar to us than looking at a simple gauge like that. So, you know, if we're gonna really, really extend human performance in quite mismatchy environments, like the colonization of Mars and long duration spaceflight, you know, institutes like the Institute for Human and Machine Cognition down in Pensacola, they're actually using research, like looking at the effects of dietary ketosis to help make humans more resilient in these environments. I think this is just sort of the beginning of what's gonna grow or what we hope will grow into a whole full-fledged, like scientific paradigm that will really help humans extend. And we have the youngest bowel hacker here, this is Isaac Fowler, Tess and Ryan's son here. He's our newest bowel hacker here. So, if he's gonna go to Mars, maybe we can, this'll be developed by the time he gets old enough. So, one of the final points, the ancestral health or plaid mismatch theory approach can potentially be as profound as the germ theory as sort of a conceptual advance, right? And how so, the germ theory was as much a conceptual and theoretical breakthrough as it was any particular set of experimental observations. And this is sort of the logic that I see, okay? The germ theory work because it established that, A, germs exist, the germs actually exist. They're actually real. And it took scientific argument, decades, to actually establish that claim, right? And then also, germs sometimes cause disease. That needed to be established. And then importantly, the early pioneers in the germ theory argue that we can take measures against these. Similarly, I think we can follow sort of a similar approach in ancestral health. This part of Darwinian medicine, arguing that, okay, mismatch effects are very real. Mismatch effects sometimes cause disease and dysfunction. And importantly, crucially, we can take measures against them, okay? So that's kind of an overview, the way I see it. And I would like to acknowledge both the Society and Central Health Society and also my graduate institution, the State University of New York in Bigampton. Importantly, my PhD advisor, David Sloan Wilson, who was a former speaker at AHS and I hope to get him back in the future years. Also, Professor Michael Rose, who was in the audience and his grad student at Grant Rutledge, he spoke here two years ago. And then my friend Richard Richards, who finally got me to actually go paleo, he's a professor at the University of Alabama. I'm forever indebted to him. And then Ken Forda at the Florida Institute for Human and Machine Cognition. And then Aaron Blaisdell, George Diggs, Tess Fowler, and all of you people, too many to mention, okay? And then my graduate colleagues and students that were in my mismatch study group this past spring. We had a little study group up in Bigampton and we really, I think, the younger minds really grasp these ideas. They don't come to this with all these preconceived understandings of disease and it makes incredible sense to them and I hope to get some of them to join us at future conferences. So I think I'm just about finishing on time so we don't have any questions. We have a question over here. Brett, the light bulb came on for me as you were talking that the concept of mismatch is kind of in that continuum with evolution. We have a environmental stressor that changes whatever species it is slightly and in there, there's going to be times when the mismatch is so bad, some in that species will die off. I guess we always kind of knew that, that we would evolve to something else under the environmental pressures and so one, a lot of people don't like the concept of evolution just partly because they've been told that the world is only like 10,000 years old and that Darwinian evolution is incorrect. But what can we do today and where are we kind of on that continuum for the human species evolving and what are some of the deleterious things that are going on with mismatch today? Okay, yeah, good question. I think the most important thing is we simply can't, I mean, do we want to wait around for another 80 or 100 generations to start to make us better adapted to junk food or do we want to try to wait and maybe step back and try to fix the mismatches that were more the root cause, because I mean, the goal of missing is to address human suffering now within one generation. We want to be better, more healthy now. So yeah, yeah, but your more general question, I mean, I come from the American South and there's great hostility toward evolution there. The thing I've been trying to argue and build bridges with Christians, including my whole friends, family, social network back home is like, failure to understand evolution is causing concrete suffering. It's like, if this was 120 years ago, like darn it, failure to understand that germs really exist, this is causing suffering, this, this even. So do we want to, God would have presumably given us these big brains so we can use them and employ them to reduce human suffering. I mean, could there be a greater endeavor for us humans to try to understand what's causing needless suffering in the universe? So, of course, there will definitely be a lot of suffering in the animals that we're gonna have to kill to eat them, but a lot of that is just part of the background suffering. And so it's not my fault. It's not yours either, so. You might be aware that microbiology is currently exploding with research showing correlations between every form of chronic disease and dysbiosis, intestinal dysbiosis. And obviously the overuse of antibiotics, the overuse of cleaning of surfaces and washing of hands with tricholocene and all these sort of things. Yes, so I'm just really curious about your parallel of the way we need to use this meta theory in the same way that germ theory created its understanding of parasites and microbes and how do we protect ourselves from those sort of mistakes? I don't know, what do you think? I mean, I think we're doing it here, right? Do you have any thoughts? When you look at the history of medicine in relation to the 19th century development of germ theory there were people who understood what was happening in the way we understand it now intuitively. So what I'm thinking is in our own time we actually need diversity of thought and we need respect for non-scientific intuitive understandings because they might actually turn out to be things that can be mechanistically proven. Yeah, I hope so. Any other questions? Come on, Dr. Rose, I know you have one. Who cuts your hair? I learned how to cut my own hair because Dan Party cuts his own hair and I want to be a cool guy with a nice quaffur like Dan Party, so. The other room and then come back in here at 410.