SoS 210: Dr. Chris Kuzawa on the Developmental Origins of Health and Disease (DOHaD)

[Music] Hey, Christina. Sarah, how are you this morning? I am doing alright. I am slowly recovering from a full-blown sinus infection that even made my upper teeth hurt. So I'm, I'm, I'm, I'm, I'm, I'm, I'm way better today than I was over the weekend, where I couldn't even hold my head up. Oh. Oh no. Oh. Oh no. Like, what if I just suck on ice cubes? Would that be okay? All I wanted was ice cream or bread and butter, not toast. Ooh. Like, I didn't want to toast it. I wanted soft bread and butter because, but the weird thing was that chewing didn't hurt. It was bizarre, but like tapping my cheek would make my teeth hurt or shaking my head would make my teeth hurt. It was so weird. It's almost like I could feel the goo in there sloshing around. [Laughter] The sludge. The sludge. And it was sludge. I mean, this is what happens when you have to get on a plane before you're fully recovered from a cold, instant sinus infection. It is a thing. It is a thing. Anyway, because our guest today is a very punctual person. Let's go ahead and intro him. Today we have on the show for the first time somehow, which I don't understand how this is his first time on the show. Dr. Chris Kuzawa, who is a good friend of the Human Biology Association and a fan of the podcast as well. And he is the John D. MacArthur Professor and Faculty Fellow at the Institute for Policy, Research at Northwestern University, quite the title. He uses principles from anthropology and evolutionary biology to gain insights into the biological and health impacts of human developmental plasticity. For our listeners who are in biological anthropology and human biology, you probably know him well for his primary field site in Cebu, which is in the Philippines, where he and his colleagues work with a large birth cohort study. And as enrolled more than 3,000 pregnant women in 1983 and since followed their offspring into adulthood. So it's been for 30 years now. This has been ongoing, which is super impressive. And like, right? And so they use this nearly three decades of data for each study participant and the recruitment of Generation 3. So we're now into the grandchildren from that original cohort to gain a better understanding of the long term and intergenerational impacts of early life environments on adult biology, life history, reproduction and health. And a theme for much of his work is the application of these principles of developmental plasticity and evolutionary biology to health and health policies. So let's bring them on. What do you say? Yes, yes. Let's see if he's wearing mustard yellow. It's going to be too weird. What if he also has plants? Oh, this will be a thing. Hi, Chris. Hi. Hey, good morning. Welcome to the sausage science, Chris. Good morning. It's great to be here. How are you doing? Doing well. We were wondering because Christina and I are both wearing mustard yellow. If you somehow randomly also wear mustard yellow today. I'm not sure I own anything that's mustard yellow. We're going to count the tiger Lego behind you. Because that's also nice. And you also have plants. I see that I have a 10-year-old or 11-year-old actually now. Yeah. I mean, Legos. Legos are the greatest toy for any age. They are. They are, for sure. For all ages. Unless you're stepping on them. And then they're the worst thing that's ever existed at that moment. But you instantly forgive them because they're Legos and everyone loves Legos. Oh, yeah. It's definitely the best thing to come out of Scandinavia since Vikings. Right. Right. Oh, speaking of Vikings, you are not on social media. You're right about that. I'm not. But I do. I do travel here and there. I do. You haven't been following my saga of duo Lingo as I'm trying to learn finish. And currently duo Lingo is obsessed with talking about Vikings. And in particular, teaching me how to ask if somebody's cat is a Viking. Really? How is this going to help me function in the day to day of Finland? Yeah. I think Dueling goes on to you, Cara. I think they know. I think they know. They don't get my needs in Finland. I think we see the limits of AI. Yeah, that's what I've heard that Dueling go recently. Yeah, it's kind of a way to go. Yeah, they fired a whole bunch of humans and they have like replaced it with AI, which is now I know why or how to ask is your naughty cat a Viking? Because it's a very important question. Yeah, I don't care about the well behaved cat. I want to know about that naughty cat. That naughty cat. They also seem to hate cats because it's always about a naughty cat, but a good dog. It's. Yeah, I don't know anymore. It's really. Every Viking cat was a naughty cat. I mean, true. I guess it depends on your definition of naughty. Actually, Viking's even have cats is the question. I'm going to go with everybody has cats because cats domesticated people. So. So as you know, as a fan of the podcast, the sausage of science is a play on words. We want to know how the science is made. How your science is made. How you the scientists are made. So we want to know, how did you get here? Tell us about yourself. We got you interested in anthropology and then more specifically what got you interested in health? We got you interested in in development. Yeah, no, it's an interesting journey for me. So I think when I was in my teens, I already knew that I either wanted to become a geologist or an archaeologist. You know, I grew up in Colorado. Well, I actually was born in Cleveland. So my family comes from Cleveland and my father, when he was in the military, he was stationed in Denver and kind of fell in love with the mountains. So we moved out there when I was six. And so I grew up traipsing around the mountains in Colorado. I spent a ton of time in the Southwest and the desert Southwest in places like in Mexico and Colorado. And Utah. And you know, the geology is amazing in all those places, but also there's just a huge, you know, you're just surrounded by incredible pre-colonial historical cultural remains of native communities and so on. Right. So it was just I was really drawn to those field based sciences. But then when I went and you know, applied to college and I was basically just applied down the street to go to see a boulder, a couple of miles from where I grew up. There was a lot of pressure to do something practical. Right. Geology was not viewed, you know, geology and archaeology were not viewed as they were more viewed as like hobbies. Right. This is not how you make a living. So it was pressure to become an aerospace engineer. Now, I have a lot of respect for aerospace engineers. We wouldn't have Mars Rovers and all kinds of amazing things without them, but this was not my aptitude at all. And it almost ended catastrophically. I was on academic probation after my first year, you know, and so on. I survived that. And then at that point, you know, I decided to change majors and I couldn't be the non geology or anthropology. And to this day, I, you know, I look back at it and I cannot remember for my life and me why I chose anthropology because I actually spent a lot more time engaging in geology. Like I've been keeping notebooks of geology. I kind of knew all the outcrops in the front range. I volunteered at the museum, you know, and paleontological displays making those and making casts and going to talks. It was really into geology, but then when it came time to actually choose a field, I chose anthropology. It's a bit of a mystery to me, but I'm really glad I did because it obviously is a fantastic field and it's worked out really, really well. So my initial experiences with anthropology, I had some opportunities to do archeological fieldwork and research, which were amazing. But gradually, those kind of those opportunities dried up. And so I ended up being able to pivot to bio archeology, which was sort of a natural transition working with Dennis van Gerber, who was there, which was a life transforming experience for me because I spent two years working on a thesis with him credible support. And it was actually to study skeletal biology and paleopathyology bio archeology, you know, using skeletal remains to reconstruct health in the past. That's what I went to do in graduate school to work with George Amelagas at Emory. And then once I got there, George was amazing. You know, that was such a great opportunity for me. But once I got there, you know, I started taking classes in this subfield that I had never really been exposed to as an undergrad, you know, because I was kind of a late comer to that major. And I was a human biology, so I was taking classes with people like Carol Worthman, who would just open my eyes to, you know, life history theory and developmental classity and critical periods and hormones and all these incredible concepts, right? And, you know, energetic trade-offs. And so I was sucked in. And that's so I within my first year, I think I switched from studying skeletal biology, which I still think is fascinating. I love skeletal biology, but I switched over to human biology. And then, you know, it's kind of a series of events that happened after that that got me to to studying what I'm actually studying today. Now I started off. I was going to work in Zaire, what it was Zaire at the time working on a project, looking at short term growth dynamics. My advisor was Michelle Lampell, and she had sort of documented these interesting short term, you know, like the kids grow the spurts basically right there. Their growth is very stable for about a month, and they'll pop up a centimeter overnight. And the idea was to look at that in an environment where there's more seasonality in terms of food availability and that kind of thing, see how that actually played out. There was a sub-o-o-o-o-o. war there and that problem, that basically was a real problem for the project I'd set up. So I ended up pivoting over to working in the Philippines. And I knew I'd been acquainted with Linda and Dare who was the PI of this long-running study in the Philippines that I've now been working on for like 26 years or something. But I was really interested in this idea of the Barker hypothesis. And maybe that's just getting a little bit ahead of things. But that hypothesis requires that you have data early in life and that you can link that to health outcomes later. And this was a longitudinal study where you could potentially do that. So I approached her with the idea of kind of implementing those ideas in this study. Up until that point it had been a pen and pencil and the Pometry type study. It hadn't really had a health component. And she said yes. And so that's what I ended up doing. You know, I worked, I lived there about a year and a half working on that study and that's what I've been working ever since. And to give folks an idea, your work has been grounded for quite some time in this framework of Dohaid, which is the developmental origins of health and disease. And you know, we have a wide range of listeners from those who are in the field to those who are not in our field whatsoever. So if you could just kind of give the quick crash course of what Dohaid or the developmental origins of health and disease is and kind of how it's been used within our field. Yeah. I'll give a little bit of a history because I think it's really interesting. So in the mid 1980s and epidemiologist in the UK's name is David Barker. He passed away a little over 10 years ago. He and his colleague, Clive Osmond, they're at Southampton University in the UK and they're epidemiologists and they looked at patterns of sort of county wide cardiovascular disease mortality within the UK. You would see that, you know, like if you had a heat map, that kind of thing. You're going to see really high rates of cardiovascular disease and some areas and lower and others. And they kind of map that onto patterns of infant mortality in those same counties, right? And they felt that there was a very strong correlation that heart disease rates today are very high in counties that had very high infant mortality rates 60, 70 years ago, right? So it suggests that heart disease and these kind of chronic diseases like diabetes and so on might have their origins in the same sort of environmental conditions that are driving infant mortality, which they knew largely related to nutrition. And so they actually concluded that paper, the abstract of that paper from 1986 and I have a quote here, it is suggested that poor nutrition and early life increases susceptibility to the effects of an affluent diet. Right? So that was sort of the beginnings of this field. This idea that under nutrition early in life might actually accelerate or increase risk for diseases that we traditionally associate with over nutrition and adulthood. So that was the first paper, but then they started to further pursue this. They found data on birth weight and they linked those to later outcomes. And they found very consistent data, which I think are now the sort of iconic data for this field. They found inverse relationships between birth weight and risk for things like diabetes, heart disease, stroke, and so on and heart attacks. Right? So the lower your birth weight, the higher your risk. And there's not a threshold. It's not like, you know, being very low birth weight is where you get the risk. It's actually the heavier you are up to a point, the lower your risk. Right? So they started documenting these relationships and they interpreted this as consistent with this idea that under nutrition early is going to elevate risk for over nutrition later. But there was a lot of skepticism about this, especially among, you know, at this point, this was not an anthropological framework at all. This was purely within public health and medicine. There's a lot of skepticism because these are data that we would describe and epidemiology as observational. They're just observing the world, right? They're not experimenting. And so you can't say much about what's actually causing what? Now, low birth weight, baby, did indeed likely have lower nutrition in utero, but it's also possible if they're mother's smoked when they were pregnant. They're also very likely going to be born into a lower SES household and therefore experience a very different environment growing up. Right? There's a lot of what we call confounding, right? There's, it could be because of nutrition, but it could be all these other things that sort of go along with low birth weight that they're not measuring that's actually driving those relationships. So that was the skepticism. But then around this time, what really became important were experimental studies in animal models. Right? So you can actually, you can't do this in humans, but you can do it in mice or rats or guinea pigs. You can restrict diet during pregnancy. And what they found is when you do that, that you get increases in diabetes and blood pressure and so on in the offspring. Right? So they were replicating the same sort of outcomes that, that, you know, barker and others were showing in relation to birth weight in humans. And really suggesting that this interpretation of there was something to this, right? The undernutrition in utero might actually be setting up biological systems in a way that increases the risk long term for these other diseases. Now, I entered graduate school in 1994 and some of this work was just starting to percolate into our, onto our radar, right? So a care worth men was, you know, kind of having us read this in human biology in her class and that kind of thing. And there was a lot of excitement about this because anthropologists had been studying what is called developmental plasticity for over a hundred years. So if you go back to sort of the founding of our field with Franz Boas, somebody who in the early 1900s showed that, you know, the children of immigrants actually were taller than their parents or the children of immigrants who were born in the United States were taller than their siblings were born overseas and that kind of thing. And so this showed that there was an effect of the environment on our development, right? At the time that was revolutionary, like if that was not known and that we would now call that developmental plasticity. But then in the middle of the 20th century, their anthropologists really started to focus on this as a way that populations adapt to their environments, right? So as nutrition improves, growth rate speeds up. Maturation happens earlier. There's plasticity in how we develop. If you move to high altitude at a very young age, right? And there's very low oxygen at high altitude. You actually grow bigger lungs to compensate for that. And these are the kinds of examples of plasticity that were sort of ingrained in us, you know, in graduate school. So this barker stuff comes into the picture and you can imagine there was a lot of excitement because this really suggested that there was plasticity way beyond what we had realized, right? So we had studied these kind of anatomical examples of it, growth, et cetera. This suggested that metabolism, physiology, hormone regulation, all these things that are sort of invisible, right? The juxtapod戈, biomarkers and other kinds of methods that these also showed plasticity. And importantly, the period of greatest plasticity was in utero. And so the environment that the fetus is experiencing and responding to and adjusting its biology and response to is not the environment out there, right? It's actually the mother's body, right? So it's cues, it's signals, it's hormones, it's metabolism of the mother's body that it's actually, that it's responding. That's how it's experiencing the environment through her body. So it just opened up this kind of fascinating set of possibilities that there's like an intergenerational form of plasticity where the mother is kind of possibly sending some information about the environment that the fetus will be born into and that type of thing. So there was a lot of excitement around this. That's kind of the very quick, not that I guess, but that's sort of the quick synopsis of the field. How it got, I think, onto the radar of anthropologists. And since then, it's become, I think, an increasing focus. And also within public health, right? So this field, which started with Barker and his work, is now there's an international association of the study of this stuff that meets every couple years, internationally in different countries. There's a yearly conference in the United States and other countries as well. So there's thousands of people that are still in this now. I have a quick anecdote I want to put in before we push out of the next question because this is a really wonderful example. And I have one for my own family that I actually tell my students all the time that that demonstrates how the environment has a huge impact on the way genes are expressed. So my grandmother was the first one born in the United States and she was born quickly after they immigrated from Italy, like pretty quickly after. And she grew to be four foot nine. I grew my grandmother by the time I was like eight or nine years old. And she has two brothers, one who was 15 years younger than her and one who was 17 years younger than her, both of whom were over six foot five. And it was just this difference of the state of the family in the nutrition and their socioeconomic status between when they first moved to the United States to when the family was finally able to be established and that you see these massive differences in height. And now of course everyone in the family born, since her two brothers have all been huge. You know my godfather six of five six six six six all of that. But the genes for height are there. And because of the conditions, she had a much more stunted growth relative to all of the descendants since then. Absolutely. Perfect example of elasticity and boas would have been very proud. That's exactly what he was demonstrating like over a hundred years ago. So very cool. I just I always thought that this idea of I mean humans right we're so capable of doing everything everywhere and so much of that is about our ability to adapt. You know the idea that it isn't just something that we can do, you know with the tools that we use as a society that we build, but that it's something that's also happening on a biological level. And that really brings me around to talking about health and talking about society and thinking about policies that we're putting in place when we when we believe that certain types of health outcomes are going to result from early life environments and intra-eater and environments. What type of impact do you think this sort of research has had? improving health and well-being when it comes to something like policy, government policy, economic policy, social policy. Yeah, well that's a great question. So on the one hand, I think that we we really have a really good sense for some of the mechanisms and some of the biology in U2L. But translating that into policies that actually harness that biology and improve health, I think it's been a lot more difficult. And there's a very good reason for it, okay? So I think naturally when these findings came out, the big hope was that we could supplement the diets of pregnant women, right? And this is going to increase birth outcomes and you know sort of put the the next generation on a better health plane or health trajectory, right? Starting in U2L. And that has been the health. But the problem with that is that even before Barker was doing his work and you know some of the do-at work that's come since, there was a long history of attempts to try to increase birth outcomes, birth weight in women by supplementing their diets, right? So in populations, especially where birth weights are lower, that's a major factor that can kind of drive or contribute to infant mortality, right? So there was a big push to try to supplement the diets of women and see if they could improve birth outcomes and therefore increase like infant survival and that type of thing. And those studies invariably failed, right? So there's tons of these studies, they've been sort of all pulled together and you basically find that there's some nudges here and there either direct some of them from the negative, some of them are slightly positive, we sort of put them all together, there's basically nothing there. And we shouldn't be surprised, right? It's like I mean on the one hand it seems intuitive that given these findings, right, that beetle nutrition has all these symptoms of effects, we should be able to feed them other more you know, energy and protein and so forth and this should help. But the problem is that every single cell in our body requires a constant supply of energy all the time, right? So I'm sitting here talking to you, my neurons are firing, my heart, you know, my myelostates and my heart are contracting, like I don't stop, my body doesn't shut down because I haven't been eating. I have all kinds of energy reserves and all kinds of ways to move nutrients around the body, right? So I'm mobilizing glycogen stores and those are being converted into glucose. If we sit here and talk for five or six hours or eight hours, I hope we don't, but like I'll start mobilizing fat and using that, right? And then beyond that I can even mobilize protein. And this is exactly what our bodies are doing, right? We don't leave, you know, the supply of energy to our cells is so essential that it's homeostatically maintained, much in the way that the temperature using the thermometer is maintained within a house, right? You sort of set it and then like the air conditioner turns on when it gets too hot or the furnace turns on when it gets too cold, it means to build, maintain stability. That is how our nutrient supply within our bodies are maintained as well. And so when you feed somebody more, you know, when you feed a pregnant woman more food, it doesn't mean that it's going directly to the fetus. It's actually going into our metabolism and that, you know, what actually ends up happening, she puts on more weight, she might have more energy to do other things, but you don't get a bigger baby as a result of that. And that has been shown time and again, I think, right? And so, one really fascinating study that looked into this is in the Gambia, in Africa, it's one of the longest running studies of sort of maternal child health and they had a giant nutritional supplementation of pregnant women there that lasted four years. And what they found again is that there was very little effect, kind of mixed effects on birth outcomes, but the women did put on weight, they had more energy, they were kind of like singing while they were working, like they were, you know, they were more quirky and energetic. And what happened is inner birth interval, that is the interval between births actually shrunk, right? And so fertility went up about 37%. And so what we see here is a very classic example of this kind of evolutionary, this idea of a sort of evolution and trade off between whether or not the body should reproduce now or put resources into reproducing in the future. And it's pretty clear that when you feed these women or calories, they're not building more baby, they're having more babies, right? And so birth weights are not going up. And I think that that gives us real insights into the challenges here of translating this basic science into something that's a policy that's, you know, that you can actually harness as a public health effort, right? Because feeding women more energy is not necessarily going to have these kinds of energy, our additional facts because it's, you know, the fetus is very buffered. And so, you know, one way that this has played out, and if anybody who's listening to this who kind of works in the field of nutrition or maternal child health will probably have come across this concept of the first thousand days. And this is an idea, like it just Google it, Google the first thousand days and then look on images and you will see that there's like 50 diagrams and logos, you know, like there's so many organizations that have organized around this. And it's really, it's sort of the simplified kind of public facing way that this dohyde work has been, has been sort of sold, right, as a policy. One organization that has really lashed onto is the Gates Foundation. And we know that the Gates Foundation, you know, they put tens of billions of dollars into public health efforts. So they have enormous influence on the kind of conversations and the priorities, you know, of this kind of research globally. They've completely locked into this, right? So if you look on their web page, they say, you know, that that are framework for understanding nutrition, basically this first thousand days framework, which emphasizes the importance of nutrition between the period of conception and two years after birth, right? And the problem with, of course, it's all very well intentioned and we should be supplementing everybody's diet, making sure that everybody has adequate nutrition. But the problem is that the period of greatest sensitivity, greatest plasticity is that fetal period. And as I've just talked about, nutrition during that period is highly buffered, right? And so yes, nutrition going to the fetus is very important in that period, but what the mother experiences during pregnancy itself is not what drives that. So this, this first thousand days framework, I mean, it's very well intentioned, but I think it's kind of, you know, it's ignoring some of this research that I talked about. Like, when you, when you supplement women who are pregnant and so forth, it's not actually getting through to the baby, right? And so I think what we need to do is think beyond that, that narrow framing. What actually drives nutrition and utero, it seems like is not the mother's pregnancy nutrition, but what she's experienced prior to pregnancy. So her weight going into pregnancy, her body mess index coming into pregnancy, we've known for a long time that those are big influences on birth outcomes. And then increasingly, we have evidence that the mother's own nutrition when she was growing up and developing can be important. So you know, there's an example of this as a big study in Guana Mala back in the 70s, where they supplement, you know, they kind of did an experiment, right? Where they supplemented different levels and different villages. And what they found was that there was a big effect of supplementing the diet of girls during childhood, that this increased the birth outcomes of their babies, right? Years in the future and had this kind of intergenerational effect. So I think nutrition prior to pregnancy chronically, you know, the mother's kind of chronic energy status prior to pregnancy, it reflected in her weight, in her body composition, but also her own developmental nutrition is also an important influence on this. But pregnancy nutrition itself, not as much. So you're pointing out a way in which this developmental origin of health and disease is not limited to the space of embryonic and fetal development and that we need to kind of start expanding that circle out. And so if maybe you could put like a finger on the finer points of what are some of the weaknesses then of the dohad framework and how we might need to start rethinking the ways in which we not only think about it, but also use it. Yeah. Well, I think, first of all, I think we have to get out of this sort of packaging of this idea as the first thousand days. I understand the appeal of that and the end, you know, it's a very simple way to kind of try to sell it to policy makers and so on, right? Like it's a very understandable sort of framing. But it's kind of detached from the biology, right? What's going on in those first thousand days is important, but what actually drives that biology is prior to the first thousand days. So we need to open, you know, widen the window and think about interventions that start much prior. Another factor, okay? So most of what I've been talking about here is the role of nutrition, right? In nutrients, macronutrients, things like energy, protein, fats, you know, those are homeostatically regulated, right? So those are resources that are required of development and they're being provided in a very regulated way. So we can't, it's sort of hard to modify that. On the other hand, stress physiology also has some of the same exact intergenerational effects. So if a mother is very stress-storing pregnancy and her cortisol levels, this hormone, this stress hormone cortisol increases, that hormone actually goes across the placenta and has the same basic effects on the fetus, right? Elevating blood pressure in the future and so on glucose and diabetes risk. So I think stress during pregnancy is is actually much more of a target potentially for interventions that are focusing on pregnancy itself because that is not as easy to buffer by the mother's body. That's actually a product of the mother's body, right? It's a signal when she's stressed out, it goes up and there's really very little that can be done to buffer that. So when we think about like interventions during pregnancy, I think the HPA axis, you know, cortisol and psychosocial stress is a very good target and therefore things that ameliorate stress like social support and those types of things are very important to focus on. If we're interested in this kind of intergenerational effective nutrition. I think the window needs to be wider. We need to think about prior to conception is probably really important in sort of driving nutrition in the next generation, or growth and development in the next generation. Those are two points. I think another factor that is super important, so much of this field, whenever there's a new field like Dohaad, or the Barker hypothesis as it was at the beginning, you're trying to convince the world that there's something here. The whole point is to demonstrate these relationships. Look, low-birth weight does lead to this bad outcome, or look at this early life stress, it leads to this bad outcome. It's about demonstrating the effects on pathology. As a result of that, there's been much less work focused on things like whether or not those effects are reversible, or are there potentially benefits of enrichment early in life? Is this all just a story about stress and scarring and doing bad things to our biology, or are there also positive pathways? They're also at work. We haven't focused as much on that. There's a lot of opportunities to focus on things like reversibility and factors in adulthood that could ameliorate the effects of early life stress, but also look at things that are actually beneficial operating through those same sorts of pathways. This is a question that students have often asked me when we talk about epigenetics. They're like, "What are the good effects of epigenetics?" I'm like, "Yeah, people don't focus." That's not how you get down to. Yeah, it is. Funding, you have to say, "Diabetes is a big problem, and here's this thing that could be helping drive it, and so that's how you get your funding." I think we need to focus fine ways to think about the positive. An example of that, I know this is politically charged in some ways, because access and ability to breastfeed is very fraught. That's an example of something that's shown to be very beneficial. There's an exposure that's actually a positive thing that we can be focused on. That's one example. To summarize your take on this as well, are you suggesting this combination of a systems approach by life stage approach as well? Like you said, the HBA access is actually critically important during pregnancy, but it also might make sense to look at it intergenerational. But then the nutritional component doesn't make as much sense during pregnancy, while it does during repair experience. It's the systems by life stage. Yes. I've actually written about, from that theme, I think you can think about the HBA and nutrition. Their intergenerational effects is having different timescales. The intergenerational effects of the HBA of stress physiology seems to be very acute. If the mother is like acutely stress during pregnancy, then it does have effects. We see this. There's studies that have looked at things like women exposed to the 9-1-1 attacks or to an ice storm, where there was massive stress in Canada and so on. You can follow those kids up and actually see the thorough effects. That cortisol is getting through. The time frame for thinking about that, and the sensitivity of that is actually during pregnancy. But for nutrition, we need to think, like you say, more systemically about it. This is a homeostatically regulated resource. It's not as malleable in response to the mother's immediate experiences. It's more a reflection of her chronic experiences. We need to take a longer view. I think that's right. We need to combine our understanding of the biology and how these systems work, but also think about how they play out, not only within a lifetime, but across multiple lifetimes. As anthropologists, our understandings of things evolve and they change. We need to pivot our research or pivot. We're approaching asking certain questions. I'm wondering, because Doha had realized so much on a systems approach, we learned so much about systems and how they change. You mentioned cortisol. You mentioned stress. These are things that we're also continuing to learn about alongside learning about how these things can impact our health long-term, short-term when there are acute changes. As there have been anything in your research particularly or research that you're really interested in, where one of those systems are understanding of one of those systems, so shifted in a way that has really made you go, oh yeah, we are asking. We got to pivot this. We are asking the wrong question. We need to approach it from this angle. What's that been like for you having to work alongside these systems that we're learning about at the same time? Yeah, that's a really good question. Honestly, I think the examples that I've just given are probably the closest to that. I think that there has been, within Doha, there's been this idea of how nutrition is going to play out across generations. The way that I'm describing it, I would say, is not necessarily how most Doha practitioners think about it. I actually think that this is an idea that I have to push or try to get people to hopefully agree with me on. This is an example of where I feel like the field, one thing that I'll say is that having been at this for a while now and thinking about biology and systems and how they play out, especially thinking about it through an anthropological lens and so on, that there's a real power to very simple ideas. Those simple ideas can take hold and actually take on the life of their own and then people organize their thinking around those ideas whether or not they're actually true or not. There's nothing to fearous. It's just I think it's the way ideas propagate and simple ideas tend to propagate easier than complex ones. There have been ideas about how these intergenerational effects work and how signaling between the mother and fetus might work that really took off but that I think were quite wrong and have been shown to be wrong now. But you kind of watch the field sort of move as this sort of at this glacial pace down this path that's driven by these ideas and you're like going, "Oh no." And then eventually it starts to become clear that maybe that's not actually how it works and people gradually forget about it. But a lot of effort was invested in thinking that way and writing about it. And so that's just one of the realities of science. I think when you work in these, like where we work, which is between anthropology, where we're thinking sort of evolutionarily and about adaptation and so on and biology and medicine, there's, you have to be especially careful about your ideas because there's a lot of opportunity to sort of just so storytell, sort of come up with ideas about what you think the adaptive story is and some of that can sort of take on a life of its own. And I think that's happened in Dohaad. I do. Watching that unfold over the years and it's been very interesting. So this becomes an important point of it's hard enough changing minds within academia as we all see, this slow continental drift kind of pace. But when you talk about the really large power and money behind it in the public realm, like you said, the Gates Foundation, you know, in the 1,000, first 1000 days, how do you start to shift that as people have been pouring resources into this and trying to make things better? And you're like, yeah, no, maybe start focusing on them before they get pregnant. And rather than the first 1000 days of life, how do you start shifting public opinion on this? Oh, yeah. Well, this is a super interesting question. So it's just a couple anecdotes from my own sort of second hand experiences with Gates. And you know, of course, I think they're doing great work. But I'm not a big fan, honestly, of their overall sort of influence, this sort of top down influence. Right. They have this huge pot of resources. They commit to a particular framework. I don't know where that framework comes from. They talk to some people, they get these ideas. And then people have to conform to it. Right. So if they want to get funding through Gates, they have to sort of, you know, shoehorn, what they're doing into that framework. And I've seen it. I've seen people that I know, you know, I'm not going to name names or it, you know, who are doing work that all of a sudden are couched in this 1,000 days framework or whatever, right? Even though it may not be the right framework, but it's what they had to do to get the funding, you know. And I, you know, I actually went to a Gates meeting a couple years ago in Ethiopia. It was not about this. It was actually about brain energetics and some other stuff. And we've done some work on brain energetics that shows that the cost, the energy cost of the brain are actually peaking out at about four to five years of age, right? So the brain requires huge amounts of energy at a point when growth has already sort of stopped. And it has all to do with the sort of neuronal complexity related to learning that's very costly. And it had been invisible, but we, you know, we put a bunch of data together and showed that. And so that would suggest that there might be real important opportunities to intervene nutritionally in four and five year olds in low resource settings, right? Like there's so much going on energetically in the brain at that point. Perhaps if you're nutritionally stressed at that age, it's going to have long term effects. And I tried to get traction on this, but it was outside of the first 1,000 days. And it was like, you're not going to get it. It's just not going to happen. So that's an example, right? So I think these foundations can have, I mean, they're, they're, obviously their intentions are good, but they can sort of stifle, you know, real conversation and, and, you know, in some cases, good science. And then I think, you know, as far as swaying public opinion, you know, this is always a problem, right? It's the simple idea that spreads. You know, when you think about why is hypertension more common among African-American Americans, right? Compared [BLANK_AUDIO] demographic groups, this idea of this slavery hypertension hypothesis that there's been this selection through the middle passage and now there's this genetic predisposition. That is an idea that is very simple and has took on head legs and is all over the place now, but there's no support for it. There's actually no evidence for it. That's an example where the simple sort of trumps the complex even if it's not correct. So I think as scientists it's incumbent upon us to try to find ways to distill down and boil down what we think is really the important message that we need to get across about our research but to do it in a way where it has legs and can actually spread. It's challenging. If we're just talking to one another, we're all talking in our own jargon. We all sort of know the same literature. You can get kind of lazy about that, but I do think it's important for all of our work. When it has public implications or policy implications, you have to put that extra effort into finding ways to package it so that it has legs and actually, you know, swastelines. Yeah, that actually is an excellent segue into what is next for you and your research, but also as an educator, as somebody who's leading scientific lines into the next fun and exciting things we're going to learn about. What are you up to? What's coming up? Who are you working with? Are you excited about any particular grad students or their work or your work with? Oh, yeah. Oh, yeah. I mean, first of all, grad students are, you know, that's what I put almost all my effort. Like that has been the great joy of my career, you know, having the opportunity to work with amazing grad students over the last couple of decades. And all it has done is helped me grow in all these different directions, right? It's just an absolute win-win, right? So I've learned so much from every grad student that I've ever worked with and that continues to be the case. And I'm working with a really great group now, you know, I'm working with six. So I don't know that I want to go through what they're all doing, but they're all working on some of them are working on topics related to Dohaad, but you know, one is working in the Yucatan, one is likely to be working in South Chicago, etc. I'm also really interested in this, the brain energetics stuff that I was just talking about. I'm really fascinated by those findings, you know, we showed that the brain is consuming most, you know, the highest rate of energy is of the brain occurs at four to five years of age. And at that age, it's using two thirds of the child's resting energy, right? So two thirds of the calories that they're consuming at rest are going just to keep in their brains doing. And this has had massive implications for things like other trade-offs, right? So like, if you're putting more energy into your brain, there's less to go around to other things. And so growth rate is at its slowest at that age, you know, there's all these other kinds of trade-offs that are likely at play. That is an area that I'm super, super excited about, you know, it's not easy to study because it involves non-invasive imaging of the brain and kids and trying to get it energetics. It's, you know, there's some experimentation that we're working through with that, but that's an area that I'm really excited about. And then we're actually just finishing up a five-year study in the Philippines. You know, we didn't really talk too much about that study, you know, so we talked about Doha and the effects of really environments on later health. That is what I've been studying in the Philippines, right? Using this study that I mentioned at the beginning of the podcast, it's a study that began in 1983, enrolled more than 3,000 women who were pregnant at the time. The original focus was looking at the effects of breastfeeding on infant survival, right? So that was, it was designed by economists to try to understand if formula companies, like Nestle, that were promoting formula use were actually increasing infant mortality rates and they show that they were. But now that study continue to follow those kids and now they're like, they're in their 4041 and they have kids their own, so it's a three-generation study. So we've been doing that. I've been working on that for about 26 years and we're just finishing a five-year study where we're, we're going to be looking at what's called epigenetic clocks. So, you know, Cara brought up epigenetics earlier, right? So we inherit from our parents, we inherit certain genes and whether or not those genes are actually expressed or not is influencing, you know, whether they're turned on, right? And create the proteins that have the effects on the body is influenced by these kind of chemical marks called, you know, that are sort of within the umbrella of epigenetics. And they can be modified by the environment. There's, you know, there's all kinds of interesting aspects of epigenetics, but they've developed these clocks that sort of use these markers, right? They're regular changes that occur in epigenetic markers with age that allow you, for instance, to protect someone's age very accurately. And they've been, you know, they've shown that like if you're actual chronological age, right? Like let's say that your epigenetic age says that you should be 36, but your chronological age is actually like 32, right? So your epigenetic age is sort of accelerated. That shows in a way that you're kind of aging fast, you know, so your biological age is accelerated and that actually predicts increased mortality in the long run. So we're using those kinds of kinds of clocks and using the data in our sample to try to understand what influence is the pace of aging and healthy aging in the population. So that's a big study that we're, you know, we've been working on for about five years that I'm really excited about and some of those data will finally be, we'll be putting all that together in the next year or so. Very cool. And that'll be some really exciting work coming out of Sibu, which is so much has come out of that already and it's always fun to see what the next evolution of that project is. So as we wrap things up, we always like to end with a bit of a fun or silly question and we change it from season to season. And this season we are trying and for people at home, I just used air quotes, trying to bring back a talent show for the human biology association meetings. Oh my gosh. And so Chris, if you were to take part in an HBA talent show, what would your talent be? I would probably be a good heckler. Which is just like wander around poster sessions and heckle people. I don't think I have a talent that's performative. I was, you know, like what are my hobbies? Sure, we can go with that. They're unrelated to anything that would translate. I'm trying to think, I used to play guitar. But it's been a long time and I was mostly playing stuff that would not be cool now, you know, like early metal. You could see how quickly your guitar playing clears the room. Yeah, no, we could do that. You could do it. You could do it. Which are the other players. I could be the last one to go when you need to get rid of it. Get out. For sure. It's it's clothing time. Put Chris on stage. Well, I think it's a great idea and I would love to see it. I'm not sure I'd be like the best performer, but I think it's a great idea. I'm just trying to push the effort to every person who gives a podium talk gets walkup music of their choice. That's what I think that's a great idea. Like wrestling. Like I totally want to play Apple Bottom Jeans as I walk up to the podium to give a talk. This is this has been my dream for a decade. That's awesome. I love it. So, someone will let me do it someday. Anyway, Chris, it has been absolutely wonderful hearing about the history of Doha. I don't know if many people know about that history. And so I think this is going to be a very useful podcast for the classroom for a lot of folks listening to this. So thank you for not only showing the history, but your experience, and where you hope the field is going to go in the future. Thank you so much for that. And for sharing your time with us today. Oh, I love this podcast. This is such a resource for our community. I really appreciate that you run it. And I really appreciate having this opportunity to talk to you this morning. So thanks so much.