877: Studying How Dynamic Biological Systems Shape Health and Aging - Dr. Alan Cohen

Introduction to Alan Cohen

0:00Hey everyone, and thanks for joining me today for episode 877 of the People Behind the Science podcast. I'm your host, Dr. Marie McNeely, and I am thrilled to be speaking with our guest, Dr. Alan Cohen. This episode is made possible with support from our sponsor, Innovative Research. Innovative Research has provided scientists with quality lab products made in Novi, Michigan, for more than 20 years. Their portfolio includes human and animal biologicals, assay and ELISA kits, antibodies, and more. Products can be purchased directly from their

0:30website by credit card or purchase order at www.innov-research.com. That's www.innov-research.com. They offer small quantities, bulk purchases, and custom orders. From human whole blood to specialized antibodies, Innovative Research has what you need to succeed in the lab. And today, Alan is going to share some of his insights and stories. So listeners, get ready to meet another one of our wonderful people behind the science.

1:02Every day, discoveries are made that will change our understanding of the world around us. Dr. Marie McNeely is here to bring you the brilliant minds who are making these discoveries so they can share their incredible stories and take you on an amazing journey. Welcome to People Behind the Science. Hello, everyone, and welcome to People Behind the Science. Today, I am excited to be speaking with our guest scientist, Dr. Alan Cohen. So, Alan, welcome to the show today. How are you?

1:38I'm doing great. Thank you for having me. It's really a pleasure to be here. Well, Alan, I'm excited to have you with us, and I'm looking forward to learning more about you and your work in our conversation today. But first, let me take a moment to tell our listeners a little bit more about you and how you got to where you are today. So, listeners, Alan is Associate Professor of Environmental Health Sciences, Chair of Biological Complexity and Healthy Longevity, and Co-Director of the Science of Health Program and the Robert N. Butler Columbia Aging Center

2:08at Columbia University. He received his Bachelor of Science degree in Biology and Asian Studies from the University of Michigan, Ann Arbor, and he was awarded his PhD in Biology from the University of Missouri-St. Louis. Afterwards, Alan completed postdoctoral research at Johns Hopkins University, the University of Toronto, and the University of Sherbrooke. He served on the faculty there at the University of Sherbrooke for about 12 years before accepting a position there at Columbia in 2022. And listeners, Alan has received various awards and honors, including the Canadian Institutes

2:41of Health Research, or CIHR, Institute of Aging New Investigator Prize of Excellence in Research on Aging, as well as the CIHR New Investigator Salary Award. And Alan, today we're excited to get to know you more as a scientist, of course, but also just generally more as a person. So, can you tell us

Martial arts and dance hobbies

3:00what do you like to do when you're not doing science? The two things that I do, and one of them I think surprises a lot of people, I do Aikido, the martial art. Oh, cool. I lived in Japan when I was younger and I learned Aikido and I still do that regularly. But the other one that surprises people is contact improv dance. This is a type of dance where you come up to somebody on the dance floor and you find a point of contact between your bodies and you just go with it and you don't know what's going to happen. It can be acrobatic, it could be meditative, it could be silly, and you

3:32just kind of feel what's the energy between these two people. And as much as this might sound like something very far from science, I think that the way that two people interact, or sometimes more than two people, it can be surprising how that actually informs my science as I think about complex dynamic systems and how systems interact with each other. I actually get a lot of inspiration from the dance that helps the science. So that's probably my favorite thing to do in my free time. Well, that sounds amazing. And I don't think I've ever heard of contact improv dance. How did you come across it and get interested in it? I came across it because it came out of Aikido. So Aikido,

4:07the martial art, is based on the way that two people interact with each other and they use each other's momentum and so forth. So then a modern dancer who had done Aikido fused the Aikido into modern dance and that became contact improv. So I'd heard about it because there's some people in those same circles. And then when I tried the dance, which was much more recently, but I felt like I wish I'd been doing this my whole life, but I kind of feel like I have been doing it my whole life. So it's a lot of fun. You can Google it, contact improv and find videos. It's a lot of fun.

Theoretical biology and aging

4:34Listeners will definitely have to check this out. And you mentioned that your hobbies inspire your science. I'd love to talk about your science next, Alan. So how do you describe what you do in the lab then to someone who is outside of your field or perhaps outside of science altogether? This is a question, as scientists, we're supposed to have this 30-second answer to that question that we can give to anyone, right? And my answer always depends on who I'm talking to. And there's so many ways I can frame it. But broadly, I like to think of myself as a theoretical biologist. I'm wondering, what is life? And it all started thinking about what is aging and why some species

5:08age and others don't. Why do some species live longer than others? So I was coming at it from an evolutionary biology perspective. But the deeper I've gotten into this question, the more I start to think that the question of what is aging is kind of the same as the question of what is life? So as I've gone on in my research, I've started to learn about complex dynamic systems and to realize that when we think of biology, we've got this habit of thinking that we can like break it all down into its component parts. We can study this molecule and this cell and know what they do. But actually, in order to stay alive, all these pieces have to interact with each other to keep us in balance.

5:41And it's how they all come together that really creates life. So as I've dug deeper and deeper into this, I'm starting to realize that these complex dynamic systems that help us maintain our own internal equilibrium, they're the basis of health. And as they break down those systems, that's the basis of aging. So how can we then start to measure that? How can we start to quantify it and understand the basic nature of aging and health by understanding these processes and how our internal systems maintain their equilibrium or fail to? Very cool. Well, I'm excited to dive into some of the details of your research. And I think you're

6:14absolutely right. The field of biology is quite complex and we miss a lot of the detail and the interesting bits by taking this reductionist approach that you might see in like a textbook, for example. Yeah. And we've had a lot of success with this reductionist model, right? We've found certain drugs that work very well for a certain disease or certain molecules that had a huge effect on one process. That's where it's easy to start. If you think about genetics, right, we started with Mendel looking at single mutations that had huge effects on the color of pea flowers. And that was a very natural place to start. But as we start to understand the genetics,

6:46well, now we have lots of genes that affect a trait and they interact with each other in very complex ways. The idea that we could break things down into their component parts was a natural place to start. We had some success. And I think what we've just done is to go too far in that direction and think that that model works for everything. And particularly in the context of health, we are starting to apply that reductionist model to smaller and smaller questions. It could work very well if you've got one gene that goes very wrong and causes one big disease. And if you correct that one problem, you solve the whole thing. But when you're looking at something, let's say like

7:20diabetes, where there's many, many genes that contribute and they interact with the environment in complex ways, it becomes much harder to have that kind of reductionist approach. Absolutely. And I think health and aging are really exciting areas of research right now. And I think that can be enough to motivate you sometimes just going in the lab to answer the questions that you're excited about. But do you have a favorite motivational quote or a saying or a force that keeps you going when days are difficult or you're maybe struggling to get motivated? I don't know if it's quite motivational, but it's a quote I really love. I've got a new substack, which I call dynamic entropy. And I'm using that name partly because of this quote on entropy.

7:55So Claude Shannon, who invented information theory, he called this information entropy and he got the name from his colleague, John von Neumann, who had said to him, you should call it entropy because no one really knows what entropy is. So in a debate, you will always have the advantage. And I just thought that was hilarious. And that's become part of the reason for naming my substack dynamic entropy, but also a lot of how I think about entropy in the context of aging and how this basic force of the universe that things tend to fall apart is something that our bodies need to resist. And so

8:26I think about that quote a lot. Definitely. And I think having these sources of motivation or inspiration or just things that get you thinking can be really helpful. And not only are these quotes important, but also having these people in your life who you can bounce ideas off of and maybe who have guided you along your journey. So Alan, when you look back at your career path, are there particular people who maybe initially inspired you to pursue science or who had a major impact on you?

PhD advisor Bob Ricklefs

8:50Yeah, I think we all have figures like that. There's certainly several that I could name, but I think my choice today is a really easy one because my PhD advisor, Bob Rickcliffe, passed away a couple of months ago and he was right there in St. Louis where you are at the University of Missouri, St. Louis. I'm in the process now of organizing a lot of his former students to write a piece on his career for a journal. And I don't think there's much question that he's perhaps the most important ecologist that has ever lived. And he was just such an amazing thinker. He would sit alone in his office writing important theoretical papers. Most of his papers

9:22are a very large number are sole author papers and they are theoretical biology or he would run some data analysis on data that were published. But he would then change the field with these papers and not one field, but many fields like how does speciation work or how does growth work in nestling chicks? So he would have all of these different fields from avian physiology to life history theory to community ecology to speciation to host parasite interactions. And he reshaped all of these different fields all at once. And I look at how he did it and it's a model of science that doesn't exist

9:56anymore. He had some grants, but he didn't always have big grants. He didn't need big grants. He could be the leading ecologist without getting funding, right? And now nobody would hire somebody like him because they're not bringing in money to the university. And as his students, we were never expected to work on his projects. On the contrary, we were expected to go start from scratch and figure out our own research project. And I think he didn't think that you deserve to get a PhD if you couldn't figure out your own question. And that's something that's rarer and rarer as many PhD students come into

10:30a lab expecting to have a question spoon fed to them, to have funding for it beyond their supervisor's grant. And I'm not saying that there's nothing good about the current model, but I think there's certainly something to be said about the old model when in some ways, not that everything was perfect, but things were a lot simpler and there was less kind of bureaucracy coming into the science. So with his passing, I've been thinking a lot about that and how much he's shaped the way that I think about science as well. Absolutely. And it sounds like you had an excellent opportunity and a good experience then training with this giant in the field of ecology. And your research has obviously

11:02shifted over the years, but perhaps we could rewind back a little bit further and talk a little bit

Winding path to science

11:06more about how you got on this path to science to begin with. So Alan, do you remember the first time that you started thinking about science and wondering or asking questions about life? I've always been curious. I enjoy science class coming up through school. So certainly I was always thinking about it. I remember hating science class in sixth grade and we got spoon fed this notion of hypothesis testing in a very kind of rigid way that you're supposed to think about science. I knew that I didn't like that. I was curious about what we were learning, but I never thought

11:38about becoming a scientist until much later. I actually went for a couple of years of high school to an art school where I studied poetry. Like I mentioned earlier, I lived in Japan. I majored in Asian studies at the University of Michigan. And only after a semester of Asian studies, and I realized that the other Asian studies majors, what they did after they graduate was into work in marketing or something like that, which didn't appeal to me. Then I realized, well, I better do something. And I thought if I go study ecology, I can be out in the woods with little critters. And that sounds fun. So I shifted to biology at that point. I still didn't know that

12:08I'd go on to a PhD. It was just one route I could take, but I certainly didn't have a direct route towards the science. And even once I did decide to do my PhD, so I finished my undergrad, I decided to do a PhD looking at the evolution of aging. Things have not been at all linear since then. Like I did not stay in ecology and evolution. I shifted after my PhD towards public health. And I've gotten lots of different bits of expertise along the way in demography and physiology and complex systems. So my journey, I think, has been really kind of winding in terms of how I construct the different

12:41bits of expertise that I'm bringing to the table as a scientist. Absolutely. And we mentioned, of course, that you're at the University of Michigan for your bachelor's degree. Your PhD was here in St. Louis. Can you talk then about at the end of graduate school? There's this big decision point of like, okay, do I do a postdoc? Do I try to go into industry? Do I join a startup company? There's all these different routes that you can take. How did you decide to do that first postdoc? At that point, I think I knew myself well enough to know that whatever problems academia may have, it's the only place so that I could really be happy. And I guess what I mean by that is I just

13:14have the type of mind that digs in to things I'm curious about. And I don't want anyone else telling me what I should be studying. I just want to look at the things that interest me. And there are, I think, very few other situations where you can have the freedom to do that besides academia. So I think that was clear. But the decision to shift out of ecology and evolution, that was because during my PhD, I'd had collected all these data, figured out how to analyze them and got a lot of confusing results. And so there was no like one line take home from my PhD that made much sense and

13:46kind of set me up for what the next question would be. So I figured, well, I've learned a lot of statistics. I don't know what the next question is in ecology and evolution. Maybe I should go try to make a difference in public health. That's why I made that switch at that point. And it turns out, of course, that it wasn't always that simple either. But I've enjoyed the switch. I enjoy having both sides of my scientific self.

Transition to Columbia University

14:06Absolutely. And your postdoctoral research, as we mentioned, spanned Johns Hopkins, the University of Toronto, and also the University of Sherbrooke. Can you talk about then what that transition was like moving from a postdoc role into your first faculty position? You probably can already tell that I'm somebody who's curious about a lot of things. And I had enough success, let's say, during my PhD with fellowships that I was never really that pressed to find like one thing that I do. One of my postdocs, for example, was on malaria epidemiology in India, which is far outside of most of my work on aging and physiology and health. But I was curious and I

14:39went and I did that. And at some point, I started to realize as I was shifting to a faculty position, I need to sell myself. We're now in this world where like we're salespeople, we have to pitch who we are. And to do that, I needed to have something a little bit more focused. So over the first few years as a junior faculty person, it was a hard transition because I was trying to eliminate kind of all of the side projects that I loved so that I could have a signature that would be this is what I do. And eventually I settled on understanding complex

15:10systems theory as the thing that explained why my PhD results were a mess and that would now explain maybe what the aging process is and what health is. And so it took me a few years really to understand how I could use that idea of complex systems to kind of create my signature theme in terms of my research that I would communicate to people. I think that's a really important point because I think absolutely when you're looking at your training history, a lot of people shift across different fields, they're interested in a variety of different topics, but you really do kind of have to narrow it down to have your, like you said,

15:41signature topic that you study or area of research that you work in that you can be known for as a faculty member. And I think that can be something that's just difficult for early career researchers to learn and really hone in on what they want that to be. And we mentioned earlier that you spent over a decade there at the University of Sherbrooke. Can you talk about what led to your decision to change and move over to Columbia in 2022? Yeah. So the dean at Columbia at that time was Linda Freed, who is my postdoc supervisor from when I was at Johns Hopkins. She's very well known in aging research. She came up with the main way to

16:14measure frailty in older adults. She's a fantastic collaborator. She's maybe the other person that I would have most readily mentioned in terms of who has influenced me. And I've continued collaborating with her over the years. So around about 2020, she started trying to recruit me. And there's actually an interesting story here. I think she knew that she wanted me to come to Columbia, but she wanted to really verify that and make sure. And she also wanted to build the internal kind of political support at Columbia to get the recruitment through the process. And she wanted to convince me to come.

16:45So she had this really interesting way of doing that. She had wanted me to set up a program on the science of health at Columbia. But she didn't tell me this. She invited me to join a group that she put together on the science of health at Columbia. And she had a bunch of Columbia faculty and she invited me and then one other non-Columbia person, John Beard, to join. So we had monthly meetings for about an hour and a half for, I don't know, maybe a year or so. And we would just virtually sit around the table and discuss these questions about what is health? How could we define that? How would we measure it? Where can this science go? And by doing that, she made me want to come and work with the

17:19colleagues that she'd introduced me to and John Beard as well. She made those colleagues there want us to get recruited to Columbia. And she was able to really see, yeah, the fit's going to work. This is going to be good. So then after a year or so of that, she was now in a position to make us an offer. So John and I actually both came to Columbia after that. So it was a really interesting process of recruitment. I also had some personal reasons to want to move to New York at that point, but certainly that played a big role in it. And I love the University of Sherbrooke. I can't tell you how much that institution took care of me. And it's just a good place in a lot of ways,

17:52but it doesn't have the name recognition of Columbia University. And I had often felt there that sometimes my papers, my work doesn't get taken as seriously because I'm not coming from a big name place. And as soon as I moved, I found that that was true. And I think it's really sad that that's true. I was the same scientist I had been, but as a scientist, what's meaningful to us is that our work has an impact, that we shift other people's ideas by the work that we do. And it was very clear that that was going to happen more easily at Columbia than it had been happening at the University of Sherbrooke. Certainly. Well, it sounds like Linda is a strategic mastermind

18:26laying out this whole plot to bring everybody in. Yes. And it worked so well. It was beautiful. Well, Alan, I love this story. And I think it just shows, again, the power of networking and this sort of element of serendipity that I think plays into a lot of scientists' career path as well. Well, I very much agree. And I think this was one of the mistakes that I'd made early on is to kind of underestimate the power of these personal connections, the networking, but also the serendipity. But I think I hate telling young scientists that you have to be so strategic that

18:56you just go out and plan who you're going to meet to advance your career. I don't think that's the right way to do it. But I think you need to understand that that's how the system works, because if you're unaware of it, then things may not go well for you. But you have to do it from sincerity. You have to really interact with people because you like interacting with them and you want to interact with their science. And then when you do that well, that's when opportunities will come your way. Definitely. I think forming that genuine human connection is absolutely critical. And it sounds like things have been very successful in your lab

19:28at Columbia University. I'd love to talk more about your recent or current work. So Alan, is there a particular project that you are working on at the moment that you are just the most excited about and want to share with all of us?

Dynamic signals of health

19:40I have many, but I'm going to choose one. And that project is on dynamic signals of health. I have this fantastic PhD student, Christine Carilla. And what we're trying to do together is to understand, can we use wearables and things like wearables that have dynamic signals about what your body is doing to understand your underlying health state? So the hypothesis here is that let's say that I look at an ecosystem. People who study ecosystems can predict when is the system about to collapse, not based on is there a lot of this species or a few of that species, but on the dynamics

20:12of the species. Are the populations going up and down too abruptly? So there's this whole field of what's called critical transition theory, where you can go out and measure the dynamics of a system and predict how stable it is. So this is related to ideas of resilience, and we can do this in many different systems. And in some previous work, we've shown that we can follow biomarkers over time. And if they're too highly variable, let's say in a hemodialysis patient, that's going to mean that you're at very high risk of mortality. So we wanted to take this idea that there's a basic signature in the underlying dynamics of our health, of our bodies, that's showing how well the body's doing

20:45at maintaining its own internal equilibrium. And really the hypothesis here is that all the different parts of our body are not working independently, but that we can get towards a single signal that's getting at the overall health of that system based on the dynamics. And an analogy that I really love for this is a tightrope walker. If you think about a tightrope walker trying to keep their balance as they walk along, the traditional biomedical paradigm would say, well, when tightrope walkers fall, this muscle in the left calf tends to get contracted. So we're going to go try to find a

21:16drug that's going to decontract that muscle and they will keep their balance better. And we can all see how that would not be the right approach in that situation. And what I want to look at is is there a signal in what's going on in how muscles contract and decontract, the dynamics of what the muscle is doing that's giving us some insight into how well that tightrope walker is doing at keeping their balance. And you can imagine that the worst thing they could do would be to just freeze all their muscles in one place. Even if each muscle is in exactly the perfect position, they're still going to just slowly tip to one side and fall. But on the other hand, they don't want to be swinging

21:48too wildly back and forth either. That's also not a good thing. I haven't actually measured a tightrope walker, but I'm pretty sure that if we were to go measure different muscles in a tightrope walker, we would find that very good tightrope walkers have very small fluctuations happening all the time that look pretty chaotic. If you were to look at those muscles, contractions and decontractions, it would look very noisy. And that's probably what the signal should look like in order to keep you keeping your balance well. Now, our bodies are doing that same task, but not in two or three dimensions and thousands of dimensions every second to keep their internal balance for so many

22:20different parameters. So our hypothesis is that we can get at that balance, how well the system is doing by measuring the dynamics of one or a few different things. Christine so far has been having great success in showing that across different diseases and different conditions, we can actually get at a generalized signal of health based on dynamics we can measure from wearables. In the future, this is the sort of thing that could get very widely applied very easily and very cheaply. Very cool. So what are the signals or the things that you're measuring with wearables? Is this like heart rate, temperature? What are we talking about? Most of her work so far is with heart rate

22:54data, but we have also done some work with blood pressure, some work with respiration rate, and we are planning to bring in things like continuous glucose monitoring. And what we really want to do going forward is to understand how many signals do we need? Do we need all of this? Can we use just one, analyze it all the same way? So these are all open questions. But for the moment, most of her project has been with heart rate data. People know about heart rate variability. It's kind of a similar principle, but she's able to get a much, much stronger signal than heart rate variability

23:24with the algorithms that she's been putting together. Well, Alan, this is such a cool project, and I think you described it quite well in terms of making it accessible and highlighting the potential impacts of this work. So if you think about the future of this maybe signal of health, how could that then be incorporated to improve people's health? If you think about it, when we study health now, we actually mostly study disease. We define health as just not having a set of diseases. And the whole health care system is more of a disease care system. It's built around that idea. Part of the challenge

23:55is that what might be good for cancer might be bad for diabetes or vice versa. So many times the basic things that are good for us are good in many ways. But to the extent that there's discordance, we don't know how to deal with that. There's studies coming out every other week. It seems like coffee is good for this, but bad for that, but only if you drink it in this dose. How do we think about whether something is really just good for you in general? And I'm not sure that we're ever going to get to a single measure that covers everything. Cancer, for example, is the sort of thing where it could just happen randomly and start to proceed in ways that might

24:27not perturb that much of your internal equilibrium early on. But I do think that having this general signal of how well you're doing is something that you could talk with your doctor about. It's the sort of thing that you could measure on your own through a wearable and optimize your lifestyle. That's the sort of thing that you like doing. It's the sort of thing we can use from a public health perspective to see how well did a policy change improve people's health at the population level. And that we don't need to have these conflicting measures of the rate of this disease and that disease and what happened with BMI and mortality rates and getting kind of lost and having too many

25:00things that we're trying to measure all at once. Well, it sounds like there are a lot of exciting next steps and new directions for this line of research. And it takes a village to make important discoveries in science. And this includes the partners and suppliers who researchers work with in their labs. So we'd like to take a moment to thank our sponsor, Innovative Research, and talk about their portfolio of chemiluminescence immunoassay kits, which offer high sensitivity, specificity, and reproducibility. These kits are designed for research targeting diagnostics, pharmaceuticals, or forensics, as well as environmental

25:33monitoring, food safety, and agricultural research. Visit www.innov-research.com. That's www.innov-research.com to view their entire line of chemiluminescence immunoassay kits. And Alan, I know the project that we talked about earlier was going really well, but I know oftentimes that's not the case in science. Things go wrong or you just struggle to get momentum. So Alan, do you have an example from your career of something that you've struggled with or maybe

26:03a major failure that you've had? And if so, can you walk us through how you get through these kinds of tough times?

Overcoming academic indifference

26:10I think for me, one of the biggest challenges was getting people to listen to me. I think I was really naive, let's say, during my PhD and just thinking that if I publish good science, people will read it and they will just see, oh, he was right about this. And then they will take that into account and it will change the way the field goes. And partly that's because my advisor had had so much success in doing that. He would publish simple good papers that suddenly everybody would realize, oh, he's right. And the field would change. But we live in a different world now where there is an attention economy. So I was starting to publish papers early

26:43on about complex systems theory and nobody was listening. Nobody was interested. Nobody was paying attention. So it was this very long battle to try to get people to take my ideas seriously. I had data that I could show. I had theory that I could show. And it's not that anybody said, oh, you're wrong. It's just that they would kind of politely nod and then go back to what they were doing. And this was quite frustrating as I thought that I had a new way to understand what aging is, which is kind of the breakdown of how all these different parts of our bodies interact with each other and the loss of the coherence of that system.

27:15And it just took a lot of patience. So the struggle here was it wasn't that I couldn't get my work published. I couldn't get it published in the best journals. I would get it published in lower ranking journals. And it wasn't that I was getting criticized. It was just that I was getting ignored. And there are a couple of things that happen, I think, to change that. One is just the persistence and sticking with it until the moment was right, because now everybody's talking about complex systems theory and the interconnectedness of everything and systems biology and the things

27:46that I was saying for years. Suddenly, everybody's like, oh, we've always known that. And wasn't the case. A few years ago, some of those things, scientists were not thinking of those terms at all. But when the moment was ripe for that, the world was ready to accept that idea. Then suddenly, OK, now I could start to communicate that well. And I had to be trying to push that ahead of time. I had to be there before the world was ready and just be patient and push it. And the second factor, then, of course, as I mentioned, was my move to Columbia, which I think the shift started to happen slightly before I moved. But certainly having the name of an institution like Columbia

28:20behind you doesn't hurt in terms of being able to get your message out. Absolutely. And I'm really glad you brought this point up because there are these scientific chasms, I'll say, between new ideas and the awareness of them. So getting people in the field to even hear you. But then there's this other chasm, which I think is even broader and deeper. And that's this transition to action and application. And it sounds like you had to surmount or overcome both of these chasms in your path. Very much, very much. It won't always work. I think there are some ideas that won't catch on.

28:51But I do think that patience and persistence, when you're convinced of something, is the only thing we can do as scientists. Definitely. Well, Alan, I appreciate you walking us through some of these tough challenges that you've faced in your career. And it sounds like the momentum is really accelerating at this point. And there have been many successes that you've been able to celebrate. And we love taking a moment to acknowledge the successes in science, because I think oftentimes it's sort of the tip of the iceberg and so much toil and turmoil and struggle has gone in to get to that point where you're able to share that success. So do you have a story of a meaningful win that you want to share with us today?

Grant funding and new ideas

29:26It's funny, as I think about this question, we often think of wins as like, I got this big grant, I got funded, I can pay for my research. And I really don't feel like I want to put funding out as the success. But I'm actually going to do it in the sense that after I came to Columbia, I'm adapting, I was in Canada, trying to adapt the research system in the United States. And I struggled for several years to try to get funding here, partly because the ideas I have are still not that well accepted. They require a lot of background. It's hard to write a grant about them and various reasons. But finally, in January, I got some real funding. And the success that I want

29:59to celebrate is not actually the money. It's not that I can do what I proposed in the grant. I'd like to do that. But that's not what I want to celebrate. It's that lifting the stress of looking for money lets me have time to think again and to have fresh new ideas and to really get into the conceptual aspects of the science that I love so much. So in these last few months, since I got the funding, I've been able to make a lot of progress on setting up a substack where I'm sharing some of my ideas. I've been developing a paper on the role of entropy in aging, which I think is just

30:30such a fun subject. How do our bodies resist this tendency of the universe to try to break us down? And how do we lose that ability to resist as we get older? And what about the species that don't lose the ability as they get old? They're kind of immortal, right? This entropy and aging question, I just love it. And I've had time to think about it. I'm coming up with a framework, which I call the principles of aging, which I think is a set of principles. This is with my colleague, who's a philosopher of science, joining together to get a set of principles that I think jointly explains what aging is, which is still such an open question. It's amazing that that's

31:01an open question still, but it is. And I think we may have the answer. And it's so exciting to me to be able to actually do the science I love. And the thing that needed to happen for that was to get the people forcing me to have funding off my back. That's the win. Oh, absolutely. And I think this funding struggle is something that everyone in science can relate to today. I think this is a major challenge and it just hangs over your head, your whole career from these predoctoral fellowships to postdoctoral fellowships. And then the pressure really turns up when you hit the faculty

31:32stage and you're responsible for supporting your lab. So Alan, can you walk us through, I guess, just the ups and downs of that process for you and what the experience was like when you finally got that notification that the grant was successful? I can probably talk to you for much longer than you'd like about the funding system. But as we try to come up with a system to get money to researchers, we put in place things that seem fair, that have a good rationale, but end up structuring the system in ways that I think really harm the science. So in order to get a grant from NIH or similarly from the Canadian Institutes of

32:07Health Research need to convince three reviewers that your idea is really good. And the competition is so tough that if any one of them doesn't love it, you're not going to get through. So the only way to do that is to avoid anything controversial. We've systematically eliminated the possibility to fund anything controversial by having these gatekeepers as to what is good science. For the kind of work that I do where I'm trying to push conceptual boundaries, that's a challenge. I need to find a way to communicate ideas on things like complex systems, which most researchers don't know about,

32:39clearly and succinctly in a small number of pages. And I'm competing with other researchers who are, I have a colleague at the University of Sherbrooke, François Lamontagne. He's brilliant. He's fantastic. But his research questions are very simple. He wants to look at how does the use of vasopressors in intensive care affect outcomes? And his hypothesis is that if we give people too many of these vasopressors, we work too hard to bring their blood pressure back up when the body may on his own know that it should keep it a little bit lower. So he's running big clinical trials. And

33:09he can, at the introduction to his grant, say, well, this many people die in intensive care from vasopressors. There's this many lives I could save. Like in two or three sentences, he's laid everything out and everybody is convinced he's got an important question that we should fund. So easy to convince them of that, right? When I write my grants, I need three pages to do the same thing that he did in sentence. And by putting in these gatekeeping systems, I'm not saying that he's more or less deserving than I am, but there's just different ways of doing science. And the gatekeeping systems for the funding have huge impacts on what can get funded. It puts a lot of power into the establishment

33:45in terms of allowing certain ideas through and not allowing other ideas through. So I've particularly had challenges with that because of the kinds of ideas I like to study, because I'm often a little contrarian in how I think about things. Like my ideas about the right ways to do statistics don't always align with what the reviewers are going to expect. So a lot of times I just fake it. And that's what everybody does. Everybody knows that you do that. I remember another little aside from the Canadian system, going to a workshop very early in my career on how to write a successful grant.

34:15And we were told for our budgets that never write what you're actually going to use your budget for. Here's how to pretend that your budget is going to be used well when you're not actually going to do it. A representative of the Canadian Institute of Health Research was telling us how to lie on our grants by something that we know is not true. And then when you submit, you have to like swear that everything in your grant is true. But the representative of CIHR was telling us how not to do that. And that's how kind of broken the system is, that everybody knows that what you write in your grant is not true, but they're still going to evaluate it as if it's true. For my whole career,

34:49I was successfully funded in Canada quite a bit, but it's more work for me to get the average grant than it is for a lot of researchers who are doing something that kind of fits a little bit better into what people are expecting. Definitely. So do you remember the day that you logged into the system and saw the score and were like, oh, this has potential? Oh, yes. When you get that email, and you never get an email that says you got it. You get an email that says you can log into the system and see your results. Right. So you have like a few minutes of like trying to get logged in with multi-factor authentication. And you have these few minutes of very intense stress of like,

35:21what am I going to see? I remember this grant in January. I remember the first one I got back in 2011. There's just so much excitement when you see that. But I've also at the point where I'm just used to seeing rejection a lot. And I'm not that surprised by it anymore. I'm not even that disappointed anymore. I just take it in stride. But it wears on you because you put your heart and soul into each of these grants that you write. You really invest a lot of time and energy and love into them. And most of them don't succeed. But then there's that just huge amount of excitement. I feel like I could

35:52just jump up and touch the ceiling or touch the sky when you get that good news. Absolutely. I think you definitely need to take a moment to celebrate these successes when they come around, because like I said, so much work has gone into them by that point. We like to encourage our listeners to also take a break from science, whether they're celebrating successes or just stepping back and giving themselves a moment. So one of the things we like to do is encourage our listeners to read

Book recommendations on aging

36:14broadly and provide book recommendations for everybody. So Alan, do you have a book that you've read recently or one that's been your maybe all time favorite that you want to recommend for our listeners today? Yeah, actually, I have two books. Am I allowed two books? You are allowed two books. OK. The first one is a science book. It's called Seven Decades. It came out recently. It's by my colleague Mike Girvin. Mike is an anthropologist at the University of California, Santa Barbara, and he works with a population in the Bolivian and Amazon called the Chimane. And the Chimane, they're not quite hunter-gatherers, but they're about as close as you can get nowadays. And he

36:45has been collecting since 2002 the most amazing data on the Chimane. These are people who they might wear a T-shirt, they might have a machete, but they are very, very far from any kind of industrialized lifestyle in any other way. And they don't have the diseases we have. They have the lowest rates of heart disease ever recorded, the lowest rates of dementia ever recorded. They have a little bit of diabetes, but really quite rare. Same thing for cancer. They do age, they do get older. Contrary to popular belief, they can live into their 90s, but at all ages, they're dying more than

37:18we are. And so in this book, what Mike does so well is he looks at the Chimanean detail, but he also looks at many other of these indigenous populations. The last ones in the world that we're still studying compares them historically to ancient Romans and so forth. And how did aging happen in all these different places? He's looking at it from an evolutionary perspective. So how long were we selected to live? Is there selection for life after reproduction? Do we have roles in our societies after reproduction that were shaped by evolution? He's looking at what does health look like? What

37:49does lifestyle look like? What are the lifestyle contributors to health or lack of health in different types of populations around the world? And he's also looking at some of the sociology. So what happens in indigenous society like this when you're too old to contribute anymore and you're becoming a burden on everybody else and resources are scarce. So he goes into some of what he calls death hastening rituals. And in some cases, it could actually even be murder that happen in these societies and in many societies throughout history when people are starting to become a burden in a very resource limited context. And he applies some of these lessons to how we can think about aging in our

38:23society. So it's a wild romp across so many different aspects of aging that are just so much fun to go into. That's a science book. I'd also like to recommend a book called Bewilderment by Richard Powers. And this is a novel. I've got a son who's on the spectrum. And this novel just touched me so deeply because I felt like Richard Powers just gets what it's like to have a kid who is brilliant, but in their own world and doing their own thing and not able to do what society expects of them. And he brings into this, and I don't want to give too much away, but a lot of really interesting

38:56science-y ideas too. Richard Powers' novels are very kind of science-y. They're poignant, touching. And this one in particular, it is a devastating novel, but it is so beautiful. And I just really highly recommend it. Well, Alan, these are phenomenal recommendations. I will add them to our website for our listeners to find there if they're looking for another summer reading book to pick up. And I think one of the things that we've just only touched briefly on in our conversation are some of the opportunities that you've had to go to different places. I think often in science, this comes through as different places that you train throughout your career, but also

39:29just going to conferences, traveling to work with and meet collaborators. So do you have a favorite place that science has taken you, Alan? This is one of the great advantages of it. And I have the advantage of also being trained in ecology, which means that the field work is bringing me to interesting places kind of by definition. I made the mistake. I had a lab mate named Kevin Mattson who had the perfect PhD project. He was studying the immunology of birds on islands versus the mainland. And so he had to go to many islands to get blood samples from birds in different places and compare them. So for his

40:01PhD, he went to the Bahamas and Bermuda and the Galapagos and Hawaii. And his PhD was just traveling to all these amazing places. Mine is not quite as good. I went to Panama for some of my field work, which is still a great place to be. But one of my trips to Panama, this was crazy. I met four different people kind of randomly, like these small world connections that I knew about through Ultimate Frisbee. I've played Ultimate Frisbee for a long time and just four different people in Panama that were related by Ultimate

40:33Frisbee. In one case, I was actually sitting in the middle of the jungle. There were three or four of us working together to catch birds. And we were literally in the middle of the jungle, not a building in sight. And traipsing through the jungle comes somebody that I'd been playing Frisbee with in St. Louis just a couple months before. Oh my goodness. And it turned out that he was there because his sister was one of the field assistants at Princeton who was working on our project, right? Which I'd had no clue about. So these kinds of small world stories, like I had a friend from high school that I hadn't seen since high school. And there I was with my PhD advisor and she was in a bikini hosing down

41:07bird cages at this field site in Panama. And she sees me and she comes running over in a bikini and just like jumps on me and gives me a giant hug. And there I am with her clinging to me and my PhD site supervisors looking on, chuckling. So that trip to Panama with those kind of random connections was just so much fun. That's amazing. So did you get everyone together for an Ultimate Frisbee game? We certainly did play there, but one of them was in the airport on the way home and they were kind of scattered enough that we didn't all get together for a game. Well, what was it like then doing research in Panama? Was this your first big international research

41:39experience? Yeah. And the Smithsonian Tropical Research Institute has a field station there. They were all set up with, there's actually several different field sites. We were in a village called Gamboa, which has houses that get rented out to the researchers who come. It's very peaceful and calm. And then you go into the woods to do your sampling, whatever research project you're doing. So it's a lot of fun. I was working on birds. I had to get up at like five in the morning. There's just something about the life that it's just so simple and easy. I remember thinking in

42:10that apartment, there's no microwave, there's no telephone. I remember there was no can opener. People there, I don't know if it's everybody, but at least people that I saw would just take a giant knife and they would pound it into the top of a can and they would just move it around the edge and open the can that way. You didn't need a can opener. So you just had fewer gadgets and things and you weren't less happy. None of that mattered. You were just fine. And I would come back to the States and I would feel like, I don't need all this junk. And for about a week, I would be frustrated by having a phone in a microwave and a can opener. And then after a week, I was back to

42:43my old self using all these gadgets as I'd always used them. Right. But it was just a kind of a nice reminder that these aren't really adding much to our life. Oh, yeah. Help you focus on what's important, those connections and just interacting with people and doing the science, of course. Exactly. And I know the people in science are part of what makes it so fun sometimes. I think there are certainly stereotypes out there about what scientists are like that are not always positive. But I've met so many amazing, creative, fun and funny people in science. And we even talked about some of your hobbies that maybe go against the stereotypes. But do you have other stories of these quirky traditions or personalities that you've encountered that

43:17maybe help break these stereotypes that people may still have? One of the things I love the most here is just the tradition for my PhD supervisor that whenever anyone would graduate, he'd bring a bottle of champagne. And then after the graduation, you would go through this ritual of signing the bottle. Or in some cases, it was the corpus of the bottle. And then he had this collection of champagne bottles on top of one of the shelves that was like this was all the PhD students that had graduated from the lab. This was a beautiful tradition that actually I know now many of his former students, including myself, we continue this tradition of signing champagne

43:49bottles for our students that graduate. But it's just one part of it. I think there's a whole community there. During my PhD in St. Louis, our department was very strong in tropical ecology. So we would have students from all over the world who would come and maybe they had been a park ranger for 10 years in their home country. And now they're coming to do a PhD here. And then we would have parties where you get this very international feel. A lot of people from Latin America. So the salsa music was always flowing. The caipirinias were always flowing. And it was just so much fun with that community. Well, it sounds absolutely amazing. And I love this tradition of keeping

44:23that champagne bottle as a memento, a little trophy almost, of the people who pass through your lab for their graduate studies. And I think in science, having this sense of community is really helpful because you're tackling some tough questions, some big problems. But as we alluded to earlier in our conversation, things like funding can often be a barrier, but also just technology, staff and this idea of waiting for the field to catch up. So if we took away the things that normally hold you back, Alan, and you had everything, all of the resources you could dream up, feasibility was not a problem. What is the question that you would most want to answer? If I could just get all the

44:55data that I would dream of, that data would basically be continuous data on a lot of the deep biological measures that we can get in people. So like proteomics data, metabolomics data, epigenomics data, all these kinds of things, brain signals, heart rate signals, and just have it continuously monitored in people going about their daily lives so that we can see how does this all change when different things change. And I don't think we need to do controlled experiments necessarily because there's so many types of events that that event happens discreetly and then we can see what happens

45:28afterwards. So there's almost like these mini controlled experiments that are happening all the time in our lives. So I would just want to see how do all of these signals change all the time because I could spend a whole career then just analyzing those data to figure out what does health mean? How do all these different systems come together and interact together to keep us healthy? How does that break down as we age? And we're so limited in what we can actually measure, but that would be my dream. But I'll also say that referring back to the idea that maybe we don't need always to have these huge funding and these big projects. I think there's so much that we can do

46:01with what we already have. Just thinking through the ideas, like some of my most fun work now is with my collaborator, I mentioned before, Myo Lemoine is a philosopher of science. I'm just so happy with a conversation with him where we think about new ideas or my close collaborator, Martin Picard. I never have a conversation with him and come away without great new ideas. So as long

Advice on following passion

46:21as I can be doing that, I'm already really happy. Well, I think that's amazing. And I think that is another way to highlight that, like you said, some great ideas can come even without these big grants and you can make advances in just how we think about science, how we think about health, how we think about aging without having to do these big studies necessarily, just thinking about the theory and how all of the pieces come together. So I think that is fantastic. And I'd love to end our conversation, Alan, by talking about advice. I think for our listeners out there who may be going through their own paths, whether it's in science or outside of science, it can be

46:51helpful to get advice at these critical moments. So do you have a piece of advice that somebody gave you at some point that really helped you? I think the best advice is to follow your passion. I mean, this sounds so cliche, but if you don't love it, nobody else is going to love it either. When you're really passionate about something, you will find what's unique about that idea, how to make it work, how to push it forward and be patient. Don't give up. Good ideas take time sometimes. And their time, maybe not always, but often will come. So this is advice that I got from

47:27Bob Rickliffe, my PhD advisor, Linda Freed, who I mentioned earlier. Martin Picard and I talk about this of waiting for the right moment. But part of that is you have to be passionate about the thing that you're pursuing. That's what's going to give you the patience to stick with it. So I think when we feel passionate about something, I actually think there's a physiology to this, that it brings our body and our mind into alignment behind the thing that we're driving toward. And I think it will actually literally make you healthier to be passionate about what you're doing. It's good for your health.

47:58It's good for your science. It's good for your psychology. It's good for the world. So follow your passion. I love that, Alan. Listeners definitely think about what makes you excited and try and build a career around it or work it into your life in some way. And Alan, is there any other last message of inspiration you want to leave with listeners or any other last piece of advice that you'd like to share? I think I would say, like we've talked about before, that you should know the system of science, know how the funding system works, know how publications work, know how networking works,

48:28but then don't just bow down before it. Do your thing and make a little concession here and there, but don't sell your soul to the system. If it all becomes about your career, if it's all about the funding, then why are we here anyway? And I think it's easy to get sucked into it. The system almost kind of wants us to get sucked into playing the game. But it's so crucial to understand that there's a system that you have to operate in, but through it, keep your center and keep doing the things that really motivate you. Well, fantastic advice, Alan, and thanks for sharing it with us

49:00today. If our listeners out there want to learn more about you and your work or maybe get in touch, what is the best way for them to do that? The best way right now, I mentioned this briefly earlier. I've recently started a sub stack called dynamic entropy. So if you Google sub stack dynamic entropy, you'll find it, or it's science of health, one word dot sub stack.com. So really easy to find. And this is where I share all my ideas, especially these days where it takes so long to publish something that like I'm sharing ideas in more plain language before I would publish them often kind of

49:31more unpolished in the rough ideas, but I'm having so much fun with it. So I think that's the best way to see what I'm doing. And you can also get in touch with me through that. You can also find me on LinkedIn at Hallen, A-L-A-N-C-O-H-E-N at Columbia University. So I'm pretty easy to find that way. I'm Cohen Aging Lab on Twitter. So there are different ways to get in touch with me. And I'd also mention maybe that I'm organizing a conference in Montreal, November 1st through 3rd. This conference, we're going to bring together a lot of the top researchers in aging. So if you're interested in aging,

50:04this is really going to be a fun place to be. We'll have basic biologists, anthropologists, philosophers, systems biologists, experts in entropy and physics and energy. And we're all going to get together to think about aging from many different angles. And it's the third time that I'm organizing one of these conferences. And in the past, it's just the intellectual energy of getting 50 of the world's top thinkers on a topic together. It's just incredible. So if you're interested, this is the Symposium on the Biology of Aging. And this one is called the Possibilities of Aging and Health. You can just Google it. Possibilities of Aging and Health

50:38Symposium on the Biology of Aging, Alan Cohen. You'll find it pretty easily. The registration is open for anyone who wants to come listen. That would be another thing that you could do if you're interested in this. But first of all, check out the Substack, Dynamic Entropy. I think you'll enjoy it if you like anything that I've said. Well, Alan, thank you so much for sharing these resources. Listeners, definitely take a moment to check out and to subscribe to the Dynamic Entropy Substack. Follow Alan on social media and consider meeting Alan in person in November at this upcoming conference. And Alan, thank you so much for sharing all of your insights and part of your

51:08story with us today. We really appreciate you joining us on the show. What a pleasure. It's been a lot of fun chatting. Thank you so much. Well, it's been great to have you with us, Alan. And listeners, always wonderful to have you here as well. We hope you'll join us for our next episode of People Behind the Science.

51:29People Behind the Science