Site icon Dr. Kara Fitzgerald

AI, Digital Twins, and the Future of Personalized Medicine Interventions with Dr. Nathan Price

AI, Digital Twins, and the Future of Personalized Medicine Interventions with Dr. Nathan Price

New Frontiers in Functional Medicine® Podcast Sponsors

Dr. Kara Fitzgerald is eternally grateful to our sponsors who, by blogging, podcasting and advertising with us, enable me and my team to devote energy and time to writing and publication.
Rupa Health Logo

Rupa Health allows you to order, track and get results from 30+ lab companies in one, convenient, easy-to-use and free for practitioners portal.

Biotics Research Corporation utilizes “The Best of Science and Nature” to create superior nutritional supplements, available exclusively to healthcare professionals.

Integrative Therapeutics has a rich history of exclusive clinician-curated products made with premium ingredients and backed by science.

AI, Digital Twins, and the Future of Personalized Medicine Interventions with Dr. Nathan Price

with Dr. Kara Fitzgerald

Fellow clinicians, get ready for a mind-blowing conversation with Dr. Nathan Price, Chief Scientific Officer of Thorne HealthTech and author of The Age of Scientific Wellness. Imagine harnessing AI to predict outcomes of our functional interventions (diet, supplements, lifestyle) by implementing a “digital twin” model that is populated with all of your patient’s bio data. And being able to test the response of our treatments (and importantly, the synergistic response of multimodal interventions). It’s heady stuff, but amazingly, it is where we are headed today.

Dr. Price illustrates the incredible potential this technology brings for personalized evidence-based medicine, such as tailoring interventions based on microbial markers or targeting specific lifestyle changes for Alzheimer’s prevention. The podcast is a captivating exploration of cutting-edge concepts and provides a glimpse into the exciting future of healthcare. I was wowed by my conversation with Nathan and can’t wait to start kicking the tires on this baby. I know you’ll feel the same. ~DrKF

AI, Digital Twins, and the Future of Personalized Medicine Interventions with Dr. Nathan Price

In the age of “scientific wellness,” doctors will be able to spot the signs of disease years before physical symptoms manifest, and use small, highly personalized interventions to prevent illness. On this episode of the New Frontiers podcast, Dr. Nathan Price, Chief Scientific Officer of Thorne HealthTech and a pioneer in systems biology, guides us through the groundbreaking concept of the “digital twin” model, where an individual’s health data is used to simulate and predict the outcomes of various functional interventions. This AI-driven model, incorporating diet, supplements, and lifestyle data, has the potential to revolutionize our approach to treatment by allowing us to test and understand the synergistic effects of combined interventions before real-life application—truly remarkable!

We delve into the implications for Alzheimer’s disease, the microbiome, the ability to tailor interventions based on microbial markers, and address concerns like diabetes risk. This is the next generation of functional medicine, offering immediate actions individuals can take to optimize their health today, based on this cutting-edge science.

 

In this episode of New Frontiers, learn about:

  • Importance of merging personalization with scientific evidence in functional medicine
  • Objectives and challenges of the Pioneer 100 Study
  • Significance of technical variation in biomarker research and implications of site-specific studies
  • Biological age estimation and its correlation with wellness and disease phenotypes
  • Impact of microbiome composition on weight loss and metabolic pathways
  • Standard chemistries and their association with biological age
  • Genetic signatures and disease risk
  • Current and future applications of AI in healthcare
  • Development of digital twins to predict disease onset and response to interventions
  • The application of digital twins in clinical practice with a focus on Alzheimer’s disease
  • Microbiome’s influence and actionable insights
The Full Transcript

Dr. Kara Fitzgerald (00:00:04) – Hi, everybody. Welcome to a New Frontiers in Functional Medicine, where we are interviewing the best minds in functional medicine. And of course, today is no exception. I am really thrilled to be spending some time with Dr. Nathan Price. Let me tell you all about him and we will jump right into this really cool podcast. Nathan is chief scientific officer of Thorne HealthTech and author of The Age of Scientific Wellness. Previously, he was CEO of Onegevity, an AI intelligence company that merged with Thorne. In 2019, he was named as one of the 10 Emerging Leaders in Health and Medicine by the National Academy of Medicine, and in 2021, he was appointed to the Board on Life Sciences of the National Academies of Sciences, Engineering and Medicine. He has spent much of his career, or his early career, as professor and associate director of the Institute for Systems Biology, co-director with biotechnology pioneer Lee Hood of the Hood-Price Lab for Systems Biomedicine, and is affiliate faculty at the University of Washington in Bioengineering and Computer Science and Engineering.

Dr. Kara Fitzgerald (00:01:15) – He’s done a ton of stuff, basically. He co-founded Arivale after the Institute of Systems Biology, and he received a Healthy Longevity Catalyst Award from the National Academy of Medicine in 2020. He’s got a ton of peer reviewed scientific publications. You can get some of them in free full text, and I recommend that you do. In fact, we’ll link some of them in our shownotes. You’ve been influential in my thinking, Nathan. He was also chair of the NIH Study Section on Modeling and Analysis of Biological Systems and is a fellow of the American Institute for Biological and Medical Engineering. That’s a mouthful. Dr. Price, welcome to New Frontiers.

Dr. Nathan Price (00:01:58) – Thank you so much, Kara. It’s so good to be here.

Dr. Kara Fitzgerald (00:02:01) – So, I’ve known you for a while. I’ve seen you speak many times. And you and I were just reflecting a little bit on your work at the Institute for Systems Biology. And I’m in functional medicine, I’ve been on faculty at Institute for Functional Medicine (IFM) for a long time.

Dr. Kara Fitzgerald (00:02:17) – And we pride ourselves in being the clinical application of systems medicine, or systems biology. We like to think through that big lens and I’m so glad that you’ve embraced us and that you’ve embraced functional medicine. I remember stumbling upon the Institute of Systems Biology many years ago and just being a little bit intimidated and overwhelmed, but also really excited that this systems thinking was, in fact, happening. And so, I wanted to hear a little bit about that and about how you came to that, but also, you obviously discovered functional medicine, and you must have been like, wow, there’s actually people trying to apply this clinically.

Dr. Nathan Price (00:03:04) – Yeah. It’s such a great example Kara, because it’s like- Yeah, I came from the standpoint of like a hardcore scientist. Right? So, we’re building computer models and we’re diving in and it’s all, you know, NIH grants and just building that out.

Dr. Nathan Price (00:03:20) – And as I got more and more interested in applications and we became aware functional medicine, I was in Seattle at the time, so IFM is there. And, you know, we became friends with Jeff Bland and… And you know, I could go on for-

Dr. Kara Fitzgerald (00:03:36) – All of us.

Dr. Nathan Price (00:03:37) – And then you, and Laurie Hoffman and on and on and on. And so, with so many people- And it was interesting because we were very intrigued by this notion that, oh, there’s a bunch of doctors that believe, as we were coming to really believe, in prevention over treatment, obviously systems approaches where you’re taking complexity, you’re trying to personalize that to the individual. And it was interesting too, because we got pushback on some of this too, as you probably won’t be surprised by.

Dr. Nathan Price (00:04:12) – Because your very traditional doctors, they would kind of look askance at this stuff, right? They’re like, well, you know, they don’t have the right clinical trials and they don’t have the, you know, whatever. And this is somewhat anecdotal, but I’ll just share it because I started going to functional medicine meetings and I’d go to traditional doctor meetings and they’d be like, oh, you know, the science is all here and it’s not there. And, and I would say things like, you know what though, when I go to a functional medicine meeting, everyone looks amazing. Everyone looks super happy.

Dr. Nathan Price (00:04:37) – I got pulled out in one of these meetings at IFM, like onto a dance floor, which I rarely, rarely do. but I’m dancing around like… You know, Mark Hyman is there and that dude has glowing skin. He looks really healthy for his age and all the other people that were there… So I’ve said that on a number of occasions, “Well, it looks like something right is going on over there because you see that it’s working.”

Dr. Nathan Price (00:05:01) – And as I’ve gotten more and more into this space, I’ve become very, very interested in how much personalization really matters. And I’m still obviously, I’m a huge proponent of randomized clinical trials and scientific evidence and all this. We can get into that. But I think there are ways to really merge personalization in really deep ways, especially as we get into our AI conversations. That is the kind of thing that lets us get really deep, personalized evidence, but also taking this fundamental approach because we know that one solution almost never works. But if you think about things deeply and you take a systems approach, you usually can have a benefit. So, it was just really fun to get into this world and I’ve made so many friends in it and it’s been just fantastic for me.

Dr. Kara Fitzgerald (00:05:51) – That’s awesome. Well, I’m so glad you drank the extremely healthy Kool-Aid and that you joined our- I’m so glad that you-

Dr. Nathan Price (00:05:56) – No Kool-Aid at functional medicine-

Dr. Kara Fitzgerald (00:06:00) – You know, it’s interesting. Of course, functional medicine has a long history of being challenged, but systems medicine, just the movement towards systems biology, thinking of being as whole and being an environment as whole. You guys had to have gotten some pushback also. This movement to this expanded thinking is disruptive, and so of course if you go to a more traditional model where there’s kind of single variable interventions and one molecular pathway, etc., it’s going to shake things up.

Dr. Nathan Price (00:06:31) – There’s no doubt. And in fact, pushback is one of the signs that you’re on the right track. It’s not the only sign, you can get pushback on stupid ideas too.

Dr. Kara Fitzgerald (00:06:40) – Yeah, yeah.

Dr. Nathan Price (00:06:40) – You need more than that. It’s not the only sign, but it is usually a sign that you’re doing something new. I remember when we first did, you know, we’re going to get into this Pioneer 100 Study that we did, and there was a big write up about it in Science. And the headline, I forget exactly what it was, but the headline was something like, controversial or, you know, something like this. And my immediate response was, “Why not pioneering, or spectacular, or first of its kind or…”

Dr. Nathan Price (00:07:12) – And I was speaking, actually at a pharma company, when it came out. And it was interesting because one of the executives there said something to me like, that’s what you want. He said if it’s all positive, it means everyone agrees with you and it’s not anything important. And it really kind of made me think about it, that, actually, he’s like, no. That means you did something that was important because, he’s like, that’s how you know. And so, I really I appreciated that comment from him, and it was interesting because there’s so many people even in the- You know, there tends to be a schism between people, but there’s a lot of people in that world who really buy into the kind of stuff we’re doing and love it. That that machine isn’t set up necessarily for it all the time because it does its own thing. But tons of people in there really love this kind of stuff too.

Dr. Kara Fitzgerald (00:08:00) – Well, and there’s some pretty cool science coming out looking at food-based compounds. Urolithin A is a molecule that I’m interested in and kind of applying that pharma lens on it… So we can use the power, since minds are beginning to expand, we can kind of use the power of their resources and their thinking and investigate molecules that we know in our space are important.

Dr. Nathan Price (00:08:28) – Yeah, there’s no doubt about that. And in terms of Thorne, where I’m at now, that’s kind of our mantra, which is we want to bring the same level of rigor and science of the pharma and biotech space, but to the preventive space. And I think there’s a lot of us that think that way because on its face, the notion that you can pull valuable molecules, interventions, and so forth from the natural world is sort of obvious, right? It’s like, how could that not be true? But you want to do that in a deep way.

Dr. Nathan Price (00:09:01) – And that’s what really systems biology, what functional medicine aims at and so forth, is that. Where we can take so many of those, and I really think about that as it’s really like your first line pharmacy. Right? A natural pharmacy. Because if you’re having a problem there’s this notion that, well, what first can I look at in my lifestyle that makes a difference? On top of that level, what is there in the natural world that might make a difference. And then if that doesn’t work, then you get it yourself maybe more into a pharmaceutical or that kind of intervention strategy.

Dr. Kara Fitzgerald (00:09:34) – I remember when you were recruiting for the Pioneer 100 Study. We’re going to talk about this. You did this at the Institute for Systems Biology, and I tried, you know, gallantly to be one of those 100. And, I don’t know, I was after. It filled up pretty darn quickly. And-

Dr. Nathan Price (00:09:50) – We added a few extra people. It was eventually 108. We should-

Dr. Kara Fitzgerald (00:09:54) – I should have begged.

Dr. Nathan Price (00:09:55) – We were just meeting back then. We would have loved to have had you.

Dr. Kara Fitzgerald (00:09:58) – It was just so exciting. You were so exciting to me because we’ve been thinking through this systems lens, like we’re doing our darndest to think through it. And to see you actually begin to bring that to fruition was just really exciting for those of us who’ve been trying to do this in clinical practice. But you’re using AI tools, and we’re going to talk about that more. You’re sort of using where we all want to be. You’re vetting that technology and figuring it out for us. Actually, and you can talk about this, you are using a lot of the labs that we use in clinical practice now, but you were just using this, kind of, bigger lens to investigate. And it was terribly exciting. So, tell me about the Pioneer 100 Project and what you guys learned, and we’ll go on from there and what you’ve done since.

Dr. Nathan Price (00:10:45) – Yeah. So the Pioneer 100 Project is something that Lee Hood and I initiated about ten years ago. And the idea was that as we think about scientific wellness, which is in our language, which is the notion that we want to bring the same level of depth to the understanding of wellness states that we have to disease historically. And one of the big aspects of that is you’ve got to generate all this longitudinal data on people who are, by and large, healthy. And I’m sure we’ll get into all the kind of things we’ve learned off that. I will say there was a ton of pushback against this idea to a degree that I found totally irrational, but people really didn’t like it. And one of the big criticisms was that this was a giant waste of time because they said, “Look, if you don’t have an arm that is full of disease to do the case control analysis, it’s totally worthless.”

Dr. Nathan Price (00:11:36) – And that was a pretty general view. I was surprised by how vehemently people seem to hold that because I’m like, I’m wasting my life. I’m not wasting your life. If it fails it’s on me, so-

Dr. Kara Fitzgerald (00:11:47) – Yeah. What the threat?

Dr. Nathan Price (00:11:48) – What’s the threat, you know? So the Pioneer 100- But what we really had to get into then is let’s just get a general population, so we got 100 or so people, mostly in the Seattle area, there were a few smatterings of people elsewhere, and took them through a journey where we said, all right, let’s go through and we measure a lot of the different labs that you would measure. I think it was about 100 to 150 of them. And then we measured proteomics out of the blood, metabolomics out of the blood. We did microbiome sequencing out of stool. And we were doing that on an every three month cadence. We also had wearable devices that people had, and then we had health coaches that would walk them through, like, how do you make improvements in your life? And we kept track of all of those kinds of things.

Dr. Nathan Price (00:12:37) – Now, what came out of that was that we were able to show that people were able to improve their health markedly by going through such a program, and at the same time we started generating this massive data. And we were really thoughtful about how we did the collections, how we standardize collections in time and space, which we could get into. That might get a little wonky if we go through that. But there was a huge system that went through to enable that and what it meant, and I think why so many functional medicine doctors and people in that space got so excited about it, is that it started to build this layer of information that we could put underneath really personalized interventions and start tying them to really deep science and tons of molecular measurements that at the time, no one had ever measured this many things on a population of people. And so, from that standpoint, we called everyone in the Pioneer 100 pioneers because they were the first people who were going through this kind of approach, and the vast majority of individuals allowed us to use those data for scientific discovery.

Dr. Nathan Price (00:13:46) – And we’ve continued to publish paper after paper after paper on them. We still are to this day and so, that was, I think, an incredible gift to science to be able to enable that to happen.

Dr. Kara Fitzgerald (00:14:00) – And controlling for time and space, just the timing of the collection and the location? Just taking into consideration that diurnal variation or weather changes – Were you considering all of that location?

Dr. Nathan Price (00:14:15) – All of those kinds of things.

Dr. Kara Fitzgerald (00:14:18) – Wow. That’s amazing. That’s amazing actually.

Dr. Nathan Price (00:14:20) – Yeah. And some of the ways you have to deal with it- I had spent a lot of time in my lab earlier, particularly with transcriptomics studying these. We have a ton of papers on it. Because you can often predict the lab that makes a set of measurements better than the condition. And I used to give this little talk of where we’d have this cloud of points and we’d separate that and we’d see like, okay, clearly this is cancer and non-cancer. And then I would say, I just lied to you. This is lab one and lab two.

Dr. Kara Fitzgerald (00:14:47) – That’s Joe. That’s Joe’s lab over there.

Dr. Nathan Price (00:14:50) – Normal and cancer in lab one, and this is normal and cancer in lab two. And then you do the second mode and a principal component analysis, you know, decomposition, and then it would start separating out. So, there’s all of these effects and we don’t know what causes all of them, there’s just many factors. And you listed a number. Where are you at? What’s the humidity? What’s the environment in the room? Are there little differences in how somebody- There’s a million things. What we actually did was to build a system such that when all of the vendors and all the different places where we would do measurements, we would spike in controls into every single one of those. We would normalize them against something that we knew. We actually had these big mixed vats of blood, and we would split them and we would store them at each of the different locations where measurements were done, so you could spike those in.

Dr. Nathan Price (00:15:42) – And then there were tons of algorithms on the back end that would control so that your proteomics that you did in, you know, this is getting a little bit further downstream when we had the company, but you were doing, you know, in South Carolina at 2 p.m. versus the ones that you had that you ran from a group in Southern California spread around, you know, in the morning or the evening or whatever it was. And then all of that was tracked. And in fact, one of the big blood measurement companies had a spot on the board of Arivale, you know, the subsequent company, mostly just for that, so that they could see all of the things that we had done with their data and these other data types in terms of standardizing it and seeing how consistent are these place to place, location and location, time to time, and so forth.

Dr. Kara Fitzgerald (00:16:29) – That’s fascinating. When we did our study out of the National College of Natural Medicine, I consulted- Moshe Szyf was an author and a consultant for me, a mentor as an epigeneticist extraordinaire, and he said that same thing to us. He said, you have to run the study. You can’t do it remotely. You just really need to run it in one location because DNA methylation is so sensitive. You need your whole populations, just like being right there. He advised on that, and, you know, thank God we were able to do it. And then the other really crazy- Because I’m not a scientist. I’m not in your world. Let me just say this one thing and then I want to hear what you have to say. We had our specimen, our saliva specimen processed at Yale and when they put the specimen on the chip, I had to sign off on it, which meant that I had to go back to Moshe Szyf and be like, what the hell? Like each position really mattered. It could make a difference just on that chip. So it was extraordinary to me how much needs to be controlled.

Dr. Kara Fitzgerald (00:17:33) – And we were just paying attention to a handful of things. But I can appreciate all the variables you guys worked on.

Dr. Nathan Price (00:17:41) – Yeah, it’s really true. And I think the average person just doesn’t appreciate how much variability there are in these kinds of measurements. I do want to make one point: If you’re trying to learn something in science and you want to get rid of all that technical variation, then you’re right – you kind of want to locate it to one site. But if you’re trying to do something like a diagnostic, if you do that in one site, what it means is that you could actually learn something that works in that site beautifully, but the second you take it anywhere else, it doesn’t work. So I was on this committee, workshop for the National Academies of Medicine, this is like ten years ago or a little bit more, that actually went through this robustness. And one of the things that we ended up putting into those guidelines were that when you did biomarkers- Because there’s 100,000 claimed biomarkers and papers every year, two on average make it into the clinic.

Dr. Nathan Price (00:18:34) – So that conversion rate is terrible. That used to be a little bit of a point of pride for Lee and I, because in one decade we had two of them, so we felt pretty good about that.

Dr. Kara Fitzgerald (00:18:44) – That’s awesome.

Dr. Nathan Price (00:18:46) – So that was following that report. But basically, one of the things that you want to do is to deal with that uncertainty up front so that you’re actually gathering data from multiple sites and you’re machine-learning across that, because that enables you to get signals that are more robust for that transplant. So, it really depends on what your goal is. I don’t want to get too wonky on that. But that’s a-

Dr. Kara Fitzgerald (00:19:12) – Well it’s great. It’s very compelling. Yeah. And of course, I mean you want CRP (C-Reactive Protein) in Miami to be as useful as a CRP in Connecticut. No, I completely get it. But we were working- Ours was a pilot investigation. And we just, you know, we had to-

Dr. Nathan Price (00:19:28) – Totally. If it’s a small study and- Yeah.

Dr. Kara Fitzgerald (00:19:31) – It’s a different conversation.

Dr. Nathan Price (00:19:33) – And you have the cases and the controls from different places. And that happens all the time for practical reasons. And it’s really problematic from a-

Dr. Kara Fitzgerald (00:19:41) – It’s very disruptive. Yeah. Of course, I mean I can just see in ours, when we compare the cases and controls, we see different things and these guys were recruited from the same locations. Anyway, I just want to say for clinicians, functional medicine clinicians are the large portion of the audience here, and so you guys in the Pioneer 100, you were using labs that, again I want to just say, we use all the time. Standard chemistries from, I think, both LabCorp and Quest, but also, Genova tests, stuff that we’re ordering. I want to underscore it because you’ve since harvested a ton of information, and we’re going to talk about some of that research. But it’s validating for us, I think, that we’re in the right direction. It’s nice to hear. Yeah. Go ahead.

Dr. Nathan Price (00:20:27) – And those standard clinical labs were so critical because when you start measuring the microbiome, you don’t know that much about the health effects. And you start measuring the metabolome and you only kind of know health effects. It’s like a Rosetta Stone in many ways because you go in- we’ll get into this when we get into specific areas that we want to talk about – but you start to learn well, how does the microbiome affect metabolic health? Well, you’ve got to have validated markers of metabolic health that you believe in in order to ask that question and so forth. So, it really is a way for you to interpret new data types, is to have these other ones that you really understand much better.

Dr. Kara Fitzgerald (00:21:03) – To that point, you went on and developed Arivale. Am I saying that right? I’m so sorry.

Dr. Nathan Price (00:21:11) – Arivale.

Dr. Kara Fitzgerald (00:21:22) –But then you moved into looking at thousands of individuals. So, you were applying this technology- I mean, you guys were for sure, ahead of your time. You were really early in this world and we were excited about it, you know, those of us early adopters in functional medicine. But I have to believe that is a big reason that Arivale wasn’t able to, you know, isn’t here still today. However, you had a massive data set of almost 4000 people and the Pioneer 100-

Dr. Nathan Price (00:21:58) – Five thousand.

Dr. Kara Fitzgerald (00:22:00) – Five thousand. Yeah, amazing. And you learned a ton of stuff. I mean, I quote you in my book, I’ve just paid attention to your papers. They’re incredibly valuable. I just pulled open, actually for this conversation, your 2019 publication, Multi-omics Biological Age Estimation and Its Correlation with Wellness and Disease Phenotypes, a longitudinal study of at this time, 3500 individuals and you published that in the Journals of Gerontology. This is an awesome paper, you guys. This is awesome. I’m pretty sure it’s free Full text. Well, anyway, there’s a ton of information in this. It’s so yellow highlighted. You guys learned a lot from this about biological age and chronological age, whether biological age is even manipulable, if we can slow it down, the association with biological age and disease. You also began to really harvest the biomarkers around this. And to your point, standard chemistries that we’re looking at are featured broadly in here and they’re kind of linchpins in looking at bioage. I want you to talk about all of that. And then you put numbers behind the accelerated aging in certain disease states, I’ve quoted you many times, over six years on average, you know, the diabetic patient’s bioage is ahead.

Dr. Kara Fitzgerald (00:23:28) – It’s just a great paper. I recommend anybody to get it. It’s influenced my thinking quite a bit. So just talk to me about it.

Dr. Nathan Price (00:23:39) – Yeah. It was an incredible study. John Earls, who was my graduate student at the time, was the first author on that and did a ton of work on it. There’s a number of take-homes that were, I think, very fascinating. First was: How does this biological age measure change over time in people who are aiming to improve their health? And I think it’s really important to keep in mind that we develop the biological age later. We’re not targeting to it with the coaching in Arivale, but we develop it and then we go back and look at that. And it turned out that, on average in that population, people got better in terms of their biological age compared to their chronological age by 1.16 years per year, on average.

Dr. Kara Fitzgerald (00:24:27) – Amazing. Is that escape velocity? Are they going to live forever now?

Dr. Nathan Price (00:24:32) – No. If it were just a pure linear trajectory, yes. Sometimes you hear people talk like that, but the larger that delta gets, the harder it is to maintain, and there’s limits to this.

Dr. Kara Fitzgerald (00:24:43) – Right. So basically, the healthier you get it’s slowing down considerably, is what you’re saying about the delta.

Dr. Nathan Price (00:24:49) – I mean sometimes at parties you’ll joke about that. I’m going to go out the back side. You know, I got to get worried because I’m just going down like too fast or whatever. But, you know, that’s not a real worry. You’re not going to regress to childhood. Or at least not yet. We don’t have any technologies that way. But it is a pretty good measure of health. But there’s a window of what’s possible today. You can’t do it forever, certainly at this point.

Dr. Kara Fitzgerald (00:25:13) – How broad is the window? Have you figured that out yet?

Dr. Nathan Price (00:25:17) – Probably play with about 20 years or so.

Dr. Nathan Price (00:25:19) – That’s a good chunk of time.

Dr. Nathan Price (00:25:21) – Which is a good chunk of time. So, it’s 1.16 years on average. Women did particularly well. Women in Arivale were getting better at a rate of one and a half years per year. So, they were getting half a year younger on average on this metric. And men were getting better at 0.8 years per year, meaning that every year they age, on average, 0.2 years according to this metric. And so we saw that. For myself, I’ll even say- I started with a biological age that was right around my chronological age, and I was in the program for four years, and my biological age dropped by ten years, according to this metric.

Dr. Kara Fitzgerald (00:26:00) – Incredible.

Dr. Nathan Price (00:26:01) – Which I have to say, just to share a personal- That was very gratifying to me because I had kind of felt like my road through Arivale… I felt like it had helped me in many ways; cognitively I was feeling better, I had changed lots of habits. But one of the things that I had really wanted to change more than it did was my weight. And my weight had been pretty stubborn. Lose, gains really rapidly, lose gain, you know…  So I was doing kind of the usual thing. but what was fascinating to me is, at least in my blood chemistry, it just kept ticking younger, younger, younger, younger, younger. And so when that came out- Because I didn’t know who I was when we published the study. I went back and I got- Because I’m in there, but I have a random ID just like everyone else, so I didn’t know who I was. But I was able to get it and I had John look it up and I said, send it to me. How did it come out? And I was so pleasantly surprised.

Dr. Nathan Price (00:26:49) – It was one of the reasons we ended up taking the clinical lab version of the biological age, similar to what’s in that paper, and turn it into a commercial product at Thorne, because I just thought that it made a big impact on me, just to be able to see it. And so that was something that I think was very exciting from the standpoint of change. Now, another thing that we get into in that paper that is probably not appreciated as much, and it is an important point, is that you can build biological agents from various different sources. Epigenetics is the most famous, but you can do it for metabolomics. You can do it from proteomics. You can do it from clinical labs. The clinical lab-based biological age, today, is the most related to clinical outcomes. And it’s also important to note that these ages are only somewhat correlated with each other. So, if you correlate them straight up, they’re about 0.75 correlated. Well, maybe even 0.8 correlated, but that’s because they’re all strongly correlated with age.

Dr. Nathan Price (00:27:55) – If you only correlate delta age, the difference between biological and chronological age, they’re only about 0.25 correlated, which means that they share information but there’s quite different information you’re getting off of an epigenetic age, versus a clinical lab age versus a metabolic age, versus a proteomic age, and things of this nature. And we’re just starting to sort through a lot of that.

Dr. Kara Fitzgerald (00:28:17) – Tell me why using clinical biomarker-based bioages are more associated with clinical phenotype. How did you establish that.

Dr. Nathan Price (00:28:30) – So I would say that I didn’t- Well we looked at that certainly in the context of the metabolomic, proteomic and, epigenetic. I’m pulling that partly, though, out of a paper that was coauthored by Morgan Levine and Steve Horvath, where they did direct head-to-head comparison of epigenetic age versus phenotypic age, or age based on clinical labs, and compare that to outcomes, I think it was in the NHANES study, and basically an analysis of that, and then found that out. There are of course, interesting arguments for epigenetic ages and there’s a lot of cool science that’s happening on that. I haven’t been terribly involved in that, but it’s a huge aspect of the aging field and so forth, so that’s what I’m saying.

Dr. Nathan Price (00:29:21) – So, I think in some of these biological ages, it really comes down, and the first clinical study you did was actually a really good example of this, which is the need to make them actionable. I think it’s so important, because I feel like if you’re talking about an omics where all it’s going to tell you is your age back, to me it’s kind of like, gee whiz, right? It’s cool, it’s interesting, but it’s not hugely meaningful. But when you can tie a biological age with insight into what’s driving it, and a plan of action, and a way to improve your health, then it’s a driving force for preventive medicine.

Dr. Kara Fitzgerald (00:29:59) – Yes, yes, yes.

Dr. Nathan Price (00:30:00) – Scientific wellness or health care or whatever, you know.

Dr. Kara Fitzgerald (00:30:02) – Well and what you guys did that’s really super cool that I want to kind of underline and exclamation point, is that you didn’t consider biological age as part of your intervention. You guys cast this wide biomarker net, you did your interventions, which we should talk about, and then retrospectively you analyzed, you layered the clock onto it and saw these really cool findings. Because I think what’s happening now in this space, there’s just this obsession with biological age, and there’s kind of an attachment now to sort of treating the test, you know, and not the human. Or attempting to manipulate the test with certain interventions without considering the whole person. And so, to your system’s roots, you guys just turned that upside down. That’s huge.

Dr. Nathan Price (00:30:48) – Something you have to be really careful about, I forget who said it, but there’s an adage: Whenever something becomes a target, it ceases to be a good measure. And what that means is that as soon as you’re trying to manipulate a variable- And so, when we were doing the biological age in the paper, one of the things we tried to be very careful about is don’t include in the score any of the kind of things that people supplement with. Because obviously, if you’re just trying to go to a score and it has molecules in there, you could supplement with those molecules directly and you could manipulate that score a lot. But is that meaningful? And it might be health beneficial, but you haven’t proven it by the same measure, if you’re-

Dr. Nathan Price (00:31:33) – So, what you have to do is tie that to these other health measures, because what you actually care about is the degree to which the delta age, the age difference- I don’t know, I’m an engineer. Delta is how we talk. But, you know, the difference between your biological and chronological age, to what extent does that show you that you’ve improved or hurt your health, and then tying that to a plan of action. What do you do about it? And there’s so many axes to dive in on there. Chronic inflammation, oxidative radical, you know you can name them all off, cognitive reserve, you know, on and on and on.

Dr. Nathan Price (00:32:13) – And so, what I really love is this whole notion of having metrics for wellness. So not just, do I have cancer, do I not have cancer? And I think biological age is a great first example of this, but just measures that say, am I more metabolically flexible? Am I more metabolically resilient this year than I was last year? Is my cumulative inflammation burden lower this year than it was last year? Is my excess capacity for energy generation in my brain, is it better this year than last year? Things that you can focus on to get better and better at that make transition to disease less and less likely. I think those kinds of things are super important.

Dr. Kara Fitzgerald (00:32:58) – Yeah. Extremely important. So, the clock that you guys have at Thorne, there’s very tangible action steps that one can do based on the findings?

Dr. Nathan Price (00:33:12) – Oh, yeah. Absolutely. And one of the things that I’ll bring up with Arivale being early, I remember someone commented to me and they said, “Oh, I wish Arivale was still around because I want to do that microbiome test.” My immediate retort was, “Well, Thorne’s microbiome test is about 100 times better than what we had at Arivale because it’s just later.”

Dr. Kara Fitzgerald (00:33:31) – That’s right.

Dr. Nathan Price (00:33:31) – And back then we had to do 16S (rRNA) sequencing, you could look at diversity, but it was it was fairly limited.

Dr. Nathan Price (00:33:38) – It was crude. Yeah.

Dr. Nathan Price (00:33:39) – Now you can get into a lot of detail. So, actionability, right? So off of a microbiome test you can look at things like metabolic pathways. So, if you’re looking at different gene compliments, are you making too much ammonia that might make your stomach too basic and cause you digestive issues. You can see those kinds of things. We did a study, this was joint with colleagues, Sean Gibbons, in particular at ISB (Institute for Systems Biology), looking in that population at who went on to lose weight versus those who didn’t. And when we looked at baseline, once you controlled for BMI, there was not a strong signal in the metabolome or the proteome or even all those clinical labs. But there was in the microbiome. And so the microbiome was quite different for people who went on to lose, in this case, I think we had it at 1% of their body weight per month, and those who didn’t. And the big difference was, if you had a microbiome that broke down complex carbohydrates into simple sugars, those individuals did not go on, by and large to lose weight.

Dr. Nathan Price (00:34:40) – But if you had a microbiome that broke down complex carbohydrates preferentially into short chain fatty acids, it was much easier. And there was a big difference between those-

Dr. Kara Fitzgerald (00:34:49) – Fascination. Wow.

Dr. Nathan Price (00:34:51) – There’s many things that- And that one I’d want to replicate in a prospective trial, but there are mechanisms that you can look at that make quite a bit of sense and that you can dive into and understand in that way.

Dr. Kara Fitzgerald (00:35:08) – And all of this will funnel ultimately towards lowering your biological age, reducing disease risk. That’s fascinating. What were the organisms, out of curiosity. Were you able to nail down or was it just sort of action as a whole?

Dr. Nathan Price (00:35:27) – It’s across a bunch of different organisms. So, we weren’t really looking at it from the standpoint of organism by organism. It’s really-

Dr. Kara Fitzgerald (00:35:34) – It’s function.

Dr. Nathan Price (00:35:35) – Metabolic. Yeah, the gene content. And in fact, in a different study that we published in Nature Metabolism in 2021, there we were looking longitudinally at aging. And it turns out that if you stay healthy at about starting around age 50, your microbiome starts looking less and less like anyone else’s microbiomes. If you just compare them, they start being more and more distant from each other. And yet the metabolic transformations that are associated with healthy aging are largely conserved. They’re solving these similar issues, but in very diverse ways. I think in many cases, we really want to get at like, what’s the metabolic function of your microbiome as you measure it in the metagenome is much more predictive than are the actual species. And there are some differences to that. Right? C diff is obviously important because it secretes certain toxins and there are areas that we could get into. But more broadly those metabolic components are more predictable.

Dr. Kara Fitzgerald (00:36:34) – So fascinating. Well, we know that bacteria just share genes like, I don’t know…

Dr. Nathan Price (00:36:42) – All the time.

Dr. Kara Fitzgerald (00:36:43) – Playing cards or whatever, so yeah. That’s really, really interesting to me. All right. What do I want to ask you? In going back to this 2019 paper, I included it in, I created a table in the book of some of the top labs that we can get, that people who are reading it can go and ask their doctor for. And I was definitely looking at what you were seeing, because you had some standard biomarkers that any of us can ask our physicians to order, or a panel that we can put together as providers for our patients, are really pretty strongly associated beneficially or inversely with biological age. Can you talk about some of those standard chemistries? What are your favorites? And has that changed since this publication?

Dr. Nathan Price (00:37:26) – Yeah. So, the ones that really matter the most are not terribly surprising; hemoglobin A1C – fasting, more so even than fasting glucose, but both of those because metabolic health is the number one driver. And I’m sure this is what you talk about with your patients, and so forth, because you’ve got to be metabolically healthy. That is a huge driver. Just to give a comparison: Smoking as I recall, raises biological age by two years.

Dr. Kara Fitzgerald (00:37:55) – Yes. I just read that that was actually my next question. Like what’s up with that? I mean, really.

Dr. Nathan Price (00:38:01) – Less than we would have thought. Less than we would have thought. But metabolic- You know, so if you’re smoking or you’re pounding potato chips… Yeah, I don’t know. Or sedentary, right? Being sedentary is a huge killer as we know. So that metabolic health is like the primary driver. The second big driver is our hormones. Now we don’t get into a ton of detail in hormones in here because we didn’t measure tons of them, but we did it through the reserve for many of the hormones, which is DHEA.

Dr. Nathan Price (00:38:35) – And DHEA turns out to be really good from a biological age standpoint, especially female hormones because they cycle and change so much. It becomes- You can do it, but it’s a squishy target in order of trying to create a robust biological age score. And so DHEA is quite- It’s a pool for both estrogen and testosterone and so that turned out to be a very big measure. And then a third bucket that really was important were toxins. So-

Dr. Kara Fitzgerald (00:39:09) – Yeah, talk about those. Which in particular?

Dr. Nathan Price (00:39:12) – Lead was the one that we really found a lot. One of the reasons for that is that you’re not very well able to clear lead out of the body and so, it ticks up over time. One of the big factors of biological aging was just watching that increase. And of course, there’s all kinds of toxicities that come along with that.

Dr. Kara Fitzgerald (00:39:35) – And let me just say, it’s increasing not necessarily because of current exposure, if that’s what folks are thinking about. It can be liberated from bone because that’s where we sequester it to kind of prevent the toxic effect of it. So, we can see this, what we call secondary half-life, in circulation.

Dr. Nathan Price (00:39:52) – It’s a great point. Yeah, exactly. You could have even removed yourself but it’s going to continue to tick up. Mercury was another one, and old-style fillings can leach out. Actually, our CEO at Arivale had one of those, he found it when he was at Arivale, he’s talking about this publicly, so he actually got those switched. Tuna sushi was a big one. Jeff Bland, I think he shared- He was in the study.

Dr. Kara Fitzgerald (00:40:16) – Yeah, he was open about…

Dr. Nathan Price (00:40:16) – He shared that publicly, so I could say it, and he realized, okay, I’ve got to back that off.

Dr. Nathan Price (00:40:23) – We had three people that were really high in the Pioneer 100 on Mercury. Two of them because of tuna sushi, primarily and the third for the tooth. So those become really big issues and if you start tying this in with genetics, it can become even more important.

Dr. Kara Fitzgerald (00:40:41) – Interesting.

Dr. Nathan Price (00:40:41) – Because one of the things that really struck me, as just kind of a eureka moment early on, was that we didn’t actually have to just watch disease arise and go back and try to look for early warning signs. We could use genetics as a rubric to look at things right away. Because you can take data that we were getting already on people, and because we have genetic signatures that are associated with high to low risk for all kinds of different diseases, you could use the genetics themselves to just look in the population of healthy people and start to see what’s different between people who are at high and low risk for all these things.

Dr. Nathan Price (00:41:22) – So one that comes to mind is ALS. People who are at really high risk for ALS, one of the things we found is that they tended to have more heavy metals in their blood. So, when we looked at that, that’s interesting because heavy metals are a known risk factor for ALS. But we were finding this in people that don’t have the disease, but just as a function of the genetics, which suggests that if you have a polygenic risk score that tells you you’re at high risk for ALS, you’re probably less well able to clear heavy metals than the average person. So, you should be more diligent on that. And we found 750 examples like that. That’s just the first-

Dr. Kara Fitzgerald (00:42:01) – Amazing. Did you happen to- One of the reasons we can accumulate lead or toxic metals is if we’ve got one of the genes or we’re heterozygous for anything associated with hemochromatosis. Did you look at that by chance? Because that increases the quantity of transport proteins in the gastrointestinal tract, actually in the brain as well. And we just absorb easy because the toxic metals can hitch a ride on the iron transport proteins. Anyway, something I’ve observed clinically.

Dr. Nathan Price (00:42:39) – Absolutely, and it’s a really great example. And hemochromatosis because it is the most common genetic disease in Caucasians, but basically, we had people in the Pioneer 100 like that.

Dr. Nathan Price (00:42:54) – Yeah.

Dr. Nathan Price (00:42:55) – One of the people that we screened had sky high ferritin levels in their blood. And so, we got them in and they really credited us with making a huge impact on their health because he had become quite debilitated and didn’t know why. And it’s the kind of thing, like, well, your doctor should have measured that and his doctor should have- But he had concierge medicine on both coasts and they… I don’t know, they never looked. Who knows why? But we found that and the treatment for that, of course, is very simple.

Dr. Kara Fitzgerald (0043:25) – Phlebotomy. Yeah.

Dr. Nathan Price (00:43:26) – Yeah. The thing I like to say is we did this huge, high-tech study to find the one disease you can cure by leeches, but it’s…

Dr. Kara Fitzgerald (00:43:35) – It’s a huge- It’s a very underappreciated anti-aging intervention. Super potent, and it benefits the world tremendously if you give a little blood. Actually, I was just looking at my- I just got a CBC and, you know, I donate blood and just noticed that it’s time. My numbers look good. Did you happen to notice if he also had metals? Tracked toxic metals, tracking with that elevated ferritin? We’ll have to go back and look.

Dr. Nathan Price (00:44:03) – He did as I recall. He also had relatively high mercury and so forth.

Dr. Kara Fitzgerald (00:44:06) – Yeah, yeah.

Dr. Nathan Price (00:44:07) – The others I don’t remember for sure right off the top of my head.

Dr. Kara Fitzgerald (00:44:11) – I published a case report on that topic from an IFM faculty. Actually, I wrote a whole book over a decade ago and collection of case studies, and that was one of the most interesting ones, just seeing how those toxic metals can hitch a ride.

Dr. Kara Fitzgerald (00:44:31) – It’s so interesting. I also want to bring to the attention of folks, what you guys found were the standard biomarkers actually track really nicely with the PhenoAge DNA methylation test created by Morgan Levine, think you were referencing that earlier, and Steve Horvath.

Dr. Nathan Price (00:44:50) – A lot of great work. Yeah.

Dr. Kara Fitzgerald (00:44:52) – Yeah. If anybody’s familiar with the PhenoAge, the DNA methylation score is based on albumin, I think, lymphocyte count, if I’m not mistaken, alkaline phosphatase, mean cell volume, just a handful of standard labs, CRP… And you found that, like, you found-

Dr. Nathan Price (00:45:14) – We find similar things. Yeah.

Dr. Kara Fitzgerald (00:45:15) – Yeah. You really did. These are things that we can look- And then you actually added on that, again, I’m looking at the tables in the paper here, lead, A1C, etc…

Dr. Nathan Price (00:45:26) – And it’s worth noting that those were learned and regressed independently. In other words, it’s not like… If your doctor is bringing that up with you, yeah, there’s something to it. You can have independent labs that will find that and if anyone else dives in and does it, they are going to find it again too. It’s a very robust signal.

Dr. Kara Fitzgerald (00:46:19) – I want to just bring your book to folks’ attention (The Age of Scientific Wellness). You cover a lot of this stuff in the book, and it’s just really easy to read. It’s incredibly interesting. You wrote it with Lee Hood, who, if anybody doesn’t know, he was one of the guys who mapped out the human genome. Am I correct in that? Like he’s a-

Dr. Nathan Price (00:46:36) – Absolutely.

Dr. Kara Fitzgerald (00:46:37) – He’s a pretty extraordinary human, as far as I know, sort of from a distance.

Dr. Nathan Price (00:46:43) – He absolutely is. Absolutely, yeah.

Dr. Kara Fitzgerald (00:46:46) – You guys write in chapter ten, the AI (the artificial intelligence) Imperative, you write, “The realization of this vision of health care that is predictive, preventive, personalized and participatory depends on many moving parts, but no tool will be more important than artificial intelligence.” So, you’re clearly using it all over the place in your work. When is it going to be in my clinic? When is it going to be, like, real time influencing us? How can we access AI?

Dr. Nathan Price (00:47:22) – Yeah. I think it’s worth saying that AI is already being used in many ways, and then maybe I’ll talk about short term and longer term. One of the ways that we chronicle in the book that AI is being used right now is the correction of medical errors. Some of that comes around as you’re filling out an EHR and you’re going to click on a drug, for example. These drugs have long complicated names, and some of them that have very different indications sound pretty similar. So a busy or tired or, you know, physician could easily… and do, in fact at some level click the wrong box, whatever.

Dr. Nathan Price (00:48:01) – One of the ways that AI is used, and this is a program called MedAware, just simply corrects for those kinds of things. It just brings up, “Oh, did you mean this”, because it understands that it looks like this patient has kidney problems and you just clicked on something that is for heart trouble or something. And that has already been able to fix hundreds of thousands of other potential errors in the system. So, there’s some low hanging fruit that are just useful for that level. Next level up, just looking at the kind of AIs that have burst on the scene lately with ChatGPT and other things like that. There was a survey, and I believe the numbers I saw were something like 65% of doctors say that they have used that as a tool as they’re doing diagnostics and things of this nature.

Dr. Nathan Price (00:48:52) – Now, it’s not at a level where you would completely trust in those kind of things, but it is very useful if you’re trying to remember- and I use it myself, I have to say, when I’m like, oh, remind me about this or- And if it’s important I’ll double check on it, but especially the later versions are pretty good, the ability to do that. And coming very soon, I think, is going to be a big reduction on burden of physicians for chart notes and things like this. Because you can set up a recording, it can listen to you talk, it can transcribe and then you can have GPT write up notes. And then the doctor is now just reviewing the notes. Reviewing and editing, but hopefully that’s a one-to-two-minute thing instead of however long it takes. So those kinds of things are important. Another area that I think is going to come in small pieces and then large pieces are digital twins.

Dr. Nathan Price (00:49:48) – This is something that’s talked about a lot. And this is one of the things we’ve actually developed at Thorne along with a partner, around digital twins for brain health. This is what I’ve spent a lot of the last three years on, and it’s been pretty remarkable because one, it’s given me a very different view of what drives Alzheimer’s disease. Not amyloid. And I think it is really driven primarily by metabolism. And there’s many ways that you- Basically, by the need of the brain to create energy. Your brain consumes 20% of your body’s energy, and it’s 2% of biomass. So, it’s ten times more metabolically active than an average tissue. It’s a massive energy hog. You have to feed energy up to it all the time.

Dr. Nathan Price (00:50:45) – And if you starve mice, for example, the last two areas that get- You know, it will start muscle wasting. It pulls energy away from everything until the brain and the heart, and at the very, very end, it preserves the brain number one. Now the brain makes decisions, so maybe that’s not surprising, but it is the energy hog. And so, when you start looking at this, what does it take for a neuron to stay alive, then you have to satisfy that. And as you get older, your ability to perfuse oxygen into your brain goes down. And it turns out that under these conditions, you want to keep cholesterol levels and astrocytes low. APOE has a role in that. APOE4 will transport that cholesterol but slowly, which keeps concentration high, which keeps energy production neurons low, which means more neurons die, which means you get Alzheimer’s at age seventy. If you have APOE2, it’s fast, keeps that concentration low, you’re more efficient at making energy efficiently under low oxygen, and you don’t ever get Alzheimer’s, or you get it when you’re in 95 or something.

Dr. Nathan Price (00:51:55) – So, these kind of changes- Anyway, I don’t want to take too much of an aside, but you can get into these things, and what the digital twins have let us do, is we can then take this mechanism and we’ve layered on to that core mechanism the effects of inflammation, the effects of microglia, the effects of TRiMM-2 variants, vitamin D, phosphatidylcholine, every known risk factor that we can find, into a unified model of one single complex mechanism represented by this sophisticated ODE based model (Ordinary Differential Equation Model), with the Bayesian Network overlay. But basically, with this complex model- And then we’ve been able to simulate ten million digital twins of patients and when you do that, you’re able to recapitulate, very closely, the age of onset of all the different genotypes, match all the risk factors. So, we have a pretty good representation. We think we’re going to, you know, go-

Dr. Nathan Price (00:52:57) – We’ve compared it to thirty clinical trials and research studies that are out there. We’re going to be doing a prospective trial on it. Basically, what it does is it gives you this really holistic view, and these digital twins- And we’re going to get that out, hopefully to clinicians, I hope next year. We’ve got to figure out the path forward and all the regulatory hoops we’ve got to jump through and all those kinds of things. But that kind of thing is going to be- It already functions, it works. we can use blood data, we can make these measures, we can show them to people. We’ve shown them to a number of physician groups. I’m going to give a talk to the National Institutes of Health, the Alzheimer’s disease, and combinatorial therapy. I’m lucky enough to be one of the three opening plenary speakers for that meeting, and it’s going to be all about this, and we’re going to talk about it.

Dr. Kara Fitzgerald (00:53:40) – So the digital twin model will be available to us in practice?

Dr. Nathan Price (00:53:44) – Yes. That is what we’re going for. That, I think, is going to be really important, and so we’re going to be able to do that for the brain. We’re going to be able to do it for metabolism. We’re going to be able to do it for skin health. We’re going to do it for aging. Like, you can dive in and it gives you a rubric to understand how molecular level data relates to patient outcome. And you can do this in really powerful ways.

Dr. Kara Fitzgerald (00:54:15) – So we would be able to, in advance- We’ve uploaded all the patient data that we’ve got at our fingertips, and maybe you’re going to guide us to order certain things, like we want a full genome, and we want this and this, but then we can try different interventions for what’s going on in this digital twin model to see how it responds.

Dr. Nathan Price (00:54:34) – And you can simulate the likely outcome of the intervention in advance.

Dr. Kara Fitzgerald (00:54:37) – And the combination of interventions.

Dr. Nathan Price (00:54:39) – And the combinations.

Dr. Kara Fitzgerald (00:54:39) – Interactions. So you could see like, synergy of an appropriate combination or detriment or…

Dr. Nathan Price (00:54:46) – Yes, for the areas where we have enough detailed- And we’ve taken data from about a thousand papers to build this thing out. But as you take that information, then that is going to let you be able to ask the question: What’s the best intervention? How many years- So what this thing will do is actually, given the data, it will say, here’s the most likely age of onset. And there’s a probability associated with all these things. We try to take into account measurement error, error in how much we know about the effects… So, there’s a propagation. It’s a probabilistic model, but you get a range. So, we might say for this, there’s an example I often show, but it’s a fifty-year-old man and we, in this case, predict age of onset would be 61, most likely.

Dr. Nathan Price (00:55:35) – But there’s a 99% chance that he’s going to have it before 68 if he doesn’t do anything to change. But then you can give a set of interventions. It will then say whether or not the patient is likely to, you know, what percentile responder they are to each of them. And coming back to our earlier discussion on functional medicine, one of the things that stands out is that very often, all the individual interventions are predicted to do nothing. Very often. But combinations are predicted to do a lot. So, you might take something where every individual intervention is predicted to do nothing, and yet there’s a combination that will give them a decade of extra life. And we can simulate the quantitative mechanisms for why that is in every individual case, for the areas, again, where we have enough information. I gave a talk to the advisory council to the NIH director last month on this same topic, basically arguing that we should do prevention trials, not on single compounds, because when you do prevention trials on a single compound, almost everybody is a non-responder.

Dr. Nathan Price (00:56:47) – And especially when you’re talking about natural compounds and the end that you would need and the length of time in order to see that, because you’re just-

Dr. Kara Fitzgerald (00:56:54) – Yeah, yeah, yeah.

Dr. Nathan Price (00:57:00) – And the economics make no sense because if I do that for vitamin D, you know, the company is not going to make $100 billion on that over time. So I cannot justify the length and type of trial it would take to do that analysis. But if I test instead the digital twin, which is a representation of everything that I think I know about the disease, where I’m going to take measurements, I’m going to run it through the digital twin algorithm, and I’m going to do something different, personalized for every person. Now, the reason that approach in the past has not taken off amongst your hardcore scientists is because it comes off as too squishy, too often. Because if you go in and you say, well, I’m just going to do the thing that I think is right, it’s hard to say, are you changing it post facto, right after the fact, or- But when it’s written down as an algorithm, it’s still one concrete thing. The algorithm doesn’t change. It is being tested. But the fact pattern against the algorithm means that you can personalize the intervention to every single person. And when we’ve run this analysis, it shows that we should be able to get clinically validated improvement in things like mild cognitive impairment leading to Alzheimer’s, in a one-year trial with maybe a couple hundred people, instead of a trial on a single compound that would take forever. Because now you’re talking about trials where most people are responders instead of trials where almost everybody is a non-responder. And it’s radically different.

Dr. Nathan Price (00:58:38) – I gave this talk at the American Nutrition Association meeting last month because I won their science award for this year, the Alexander and Mildred Seelig Award. I gave the opening talk there and got into this because for the nutrition field as well as for functional medicine, to me, this is like the Holy grail. Because what we can do now is say, and this is where those old discussions on, like who has the scientific high ground, what we can actually say is, no, we can actually run randomized, rigorous clinical trials on individualized interventions, and the way that we’re doing these in the traditional approach is not as good. In fact, it’s not a very smart strategy, because if you’re isolating that one compound, you can never get to the end that you want to get to. You can never show the effect. You have to do these multimodal trials. And so that’s not new, right? We know that. But by writing them down in the algorithm you can really make that incredibly standardized and I think scale it.

Dr. Nathan Price (0:59:47) – And so, what I want to do is to say let’s build those for every single major category of health, run all the trials. and now all of a sudden, we have personalized, evidence-based medicine that’s incredibly rigorous, and actually at a scale of rigor that’s more, that’s better than what we have in the traditional approach. Still an RCT (randomized controlled trial), but it’s personalized. And so that I think is going to be, I don’t know- I get very excited about this topic because I just think that is the way that we can have an incredible-

Dr. Kara Fitzgerald (01:00:18) – It’s mind-blowing. Wow. You know, I was talking to Bob Rountree,  I was texting back and forth, “I’m about to podcast with Nathan. Any thoughts? “And he said, “Yeah, ask him about Alzheimer’s and the digital twins.” And I’m so glad. I mean, this obviously could and should, maybe in the future, just comprise a whole conversation because it’s extraordinary. If I’m understanding it, if I just really simplify it, if we had it in clinical practice the algorithm is consistent but what changes are my patient’s data. Because obviously their data is going to, you know, from patient to patient. So all of that – it could be obviously tons of stuff, environment, age, you know, blood biomarkers etc. – all of that is packed in there but the algorithm is consistent. And then the interventions, obviously just based on filtering through their individual phenotype, will shift their response to the interventions. Is that basically what the digital twin is?

Dr. Nathan Price (01:01:25) – Exactly, exactly. So, you might come in and it will say “For you, you need vitamin D and phosphatidylcholine and to improve your sleep profile by this amount and whatever, and you’ll get eight extra years.” And for me, it might say “You need to up your VO2 max and take phosphatidylserine and lower your basic inflammation or whatever.” And it will be some combination of things based on the biology that it observes.

Dr. Kara Fitzgerald (01:01:59) – How are you guys establishing dosing? How do you know, and are you staying within the boundaries of what’s been studied or are you jumping outside of that?

Dr. Nathan Price (01:02:09) – So we are staying within the boundaries, and that’s something we honestly could do more of as we go forward in terms of the dosing.

Dr. Nathan Price (01:02:15) – We try to calibrate it to papers around how much dose gets in and then what the effect, you know, and so might hit a receptor and then change it. One of the nice things in the digital twin models, the style that we’re using, is because it has this Bayesian Network overlay- What that means for people that aren’t familiar with Bayesian statistics, which is probably most doctors, is that it adapts itself to as much or as little data as you have. In other words, if I know nothing about you, you’re a human, it will output the average response for a human. And if I say this is a woman, it will update to the average for a woman. I say 48 years old; it adapts to that. And then I start saying, who’s pre-diabetic and has been pre-diabetic for this length of time and is APOE-4 double positive and on and on, and it adjusts the parameters, and then what the simulation does with however much or little data as you have.

Dr. Nathan Price (01:03:15) – And so that’s kind of the beauty of these kinds of approaches, because we think we can use that with doctors based on the amount of information they have and what they’re doing with their patients, in a relatively flexible way. It’s not infinitely flexible, of course, because we have to have hooks into the model of ways that we can simulate that. So, if you have like a new hypothesis that we haven’t contemplated, the model won’t magically be able to do something with that. But as those areas emerge, we can build out the biology and tack it on and it can become smarter and smarter. And this is one of the things that I really want to build going forward, is a network of physicians who are using this and sharing data back, because what we would be able to do is create a community where we’re learning at an incredible rate.

Dr. Nathan Price (01:04:05) – We’re able to do periodic clinical trials around this and update, but basically it allows for a community learning system where we get better and better at the disease. And of course, what we’re all hoping is that we ultimately get to the place where we can really effectively treat all of these conditions. And what we want to do is build the back end, the algorithms, the digital twins, provide tools and things like that, and then let the doctors build the programs and work with the patients the way that they want to. But that’s what I’m really excited about because I think we can get to this world where we get dense measurements that can be done cheaply and easily. And we spend a lot of time at Thorne on that too, like our microbiome wipe to make the sample microbiomes easier, and we’ve got this painless at-home blood measurement device, the NanoDrop.

Dr. Nathan Price (01:05:00) – So we’re trying to make these things simple. But then what I really want to do is just to tie all of that information together with these deep biological models where we get these digital twin simulations and then make them readily accessible to the community and have a lot of back and forth dialogue in terms of what are we learning and what’s working and what’s not, and iterate- And I really believe that the pace of progress for chronic disease could be majorly accelerated by building something like that, so that that’s my-

Dr. Kara Fitzgerald (01:05:30) – One hundred percent. It feels like logarithmic. When I think back in the beginning of my career, I mean, I’ve got the Boehringer Mannheim wall chart over there, like just sort of trying to hold all of this in my head when I’m interpreting lab data and thinking about mechanisms. I mean, you’ve just blown it open. That’s really, just really fascinating. Really exciting. Yeah, I would love to, you know, if you need a clinician, I would volunteer.

Dr. Nathan Price (01:05:56) – I will reach out to you.

Dr. Kara Fitzgerald (01:05:58) – Yeah, yeah. I would just love to be a part of it. We’ve got a ton that we could keep talking about. I would like to have you back maybe, I don’t know when you’re nearing launch or whatever, but just a couple more questions on this digital twin. Are we, I mean, nutrition information? How granular can it get on macronutrients, etc. or combinations? I’m sure you’re thinking about ketogenic and maybe broad macro ratios, but how granular?

Dr. Nathan Price (01:06:25) – Yeah, it’s a great point. And it’s something that we can get a lot more granular than we are right now. I actually had a really interesting conversation with Chris Palmer, who might know who wrote Brain Energy, about getting his thoughts on some of these things. A good example of that is-

Dr. Nathan Price (01:06:44) – So, phosphatidylcholine we think is a really important molecule. A lot of people do. The digital twin model predicts that for a lot of people, this becomes rate limiting. You literally run out of it, the simulations run out of this and then you start having neuronal death. And so, we looked in the nutrition literature and just said, do people who eat diets rich in phosphatidylcholine get Alzheimer’s later than people who don’t? The answer is, yeah, about three years later on average in these observational nutrition studies. And I will say it’s very different to machine-learn the nutrition literature than it is to say, “Here’s one focused hypothesis. Does it hold up when you look in?” That’s a very different thing. So that I think is very interesting. Right now, the way that we’re doing it is very granular. It’s pretty high level, which is that we ask questionnaires about the kinds of foods that people eat, and we basically bucket them into four groups of high, high-medium, low-medium, low, phosphatidylcholine.

Dr. Nathan Price (01:07:41) – And we use that as a crude measure in the model. Now, we’d much rather, as we get the metabolomics test going, say, all right, let’s look at the actual blood measures and get it more that way. And a better one would be a tissue measure and so forth. Anyway, all I want to say is that there’s so much granularity that we can get in terms of understanding that person’s diet and some things were at a very rudimentary level and some were at a really advanced level. Like glucose, you’re at a very advanced level because you can wear a CGM (continuous glucose monitor), and you can monitor it like crazy. And so, there’s this continuum like that. That’s an area that I’m really interested in. We’re working on deep metabolomics testing where we can measure maybe tens of thousands of these small molecules. And my hope is that we’re going to be able to learn, partly by tying it to the standard labs, right, as our Rosetta Stone again.

Dr. Nathan Price (01:08:35) – But figuring how do we read tons of different measures off of that big omics test that you could do inexpensively, at home, at scale. But as we start to learn how to read that information, we should be able to start informing these things at a much, much deeper level. It all goes kind of hand in hand. And then the other element that I think is so interesting is that with the technologies like the GPTs, the large language models, we can start to give back, especially if we’re doing this with physicians. There can be two-way dialogue and the algorithms can actually understand that dialogue and so, we can have conversations at a scale that we couldn’t do before. Anyway, that’s getting a little bit out there but it is a really interesting space to tie together multi-omics, digital twins that tie that multi-omics to patients, and then the AIs that really let us deliver content and information in ways that are accessible and understandable. And I think that’s going to really change the future of medicine.

Dr. Kara Fitzgerald (01:09:39) – Wow. Yeah. Yeah, I think so. So the metabolomics data that you’re looking at, going back to putting this to nutrition, are the molecules that are being absorbed and transformed etc. etc. So, you’ll be looking at the influence of- You’ll be looking at the effect of the dietary pattern more than the dietary pattern itself, which is cool.

Dr. Nathan Price (01:10:03) – Yeah, that’s what I would like to get to, and there’s some work to do, obviously, to get there, but we all know the difficulties of the questionnaires. No one wants to log their food for- a few people – but most people won’t log their food for long periods of time.

Dr. Nathan Price (01:10:19) – There’s too much lying and exceptions. And I’ll just use myself as an example, right? I’ve logged my food for periods, but you know the day I am most likely to not log is the day that I fall off the wagon, right? You’re like, oh, I’ll start logging again tomorrow. Today was bad, I was stressed or whatever. And so that’s a very human response. And there are some clear examples, like in the Pioneer 100, one of the interesting molecules is cotinine. Cotinine tells you with basically 100% accuracy if you smoke because you look for cotinine in the blood and it’s zero, zero, zero, one thousand, zero, zero, zero. That’s because, if you’re smoking, it’s in there. If you’re not smoking…

Dr. Nathan Price (01:10:59) – A few people would, maybe if you’re chronically exposed to secondhand smoke or something, you’d get some of it in there. But it’s a very clean readout. Now, foods are more complicated, but we should be able to tell the difference pretty well between – are you eating a lot of foods that have polyphenols? Well, then polyphenols will be in your blood.

Dr. Kara Fitzgerald (01:11:18) – Yeah. Exactly. Right, right.

Dr. Nathan Price (01:11:19) – The biggest confounder is that your recent diet probably matters more than the long term. And we’ve got to figure out- But there’s also, as you know, food frequency questionnaires. The one-day questionnaire is actually validated pretty well because if you take any person’s one day it’s about 80% accurate, I think is the number in terms of, you know- Because you tend to eat similar at the same time.

Dr. Kara Fitzgerald (01:11:43) – It’s fascinating. Yeah. I want to ask you about factoring the microbiome in there as well. But I want to we… Well, comment on the microbiome. Go ahead. And then I have one more final question for you.

Dr. Nathan Price (01:12:03) – I’ll comment on the microbiome for-

Dr. Kara Fitzgerald (01:12:05) – Well, I mean, I’m thinking about the transformation of our nutrients, our macronutrients through the microbiome and then the polyphenols and the postbiotic compounds that are absorbed and all of that. I mean, in theory, if your food frequency questionnaire is BS, I mean, you’re going to just obviously have a much different picture. I’m just wondering, but I guess maybe more fundamentally, my question is, factoring the microbiome influence on everything into the digital twin.

Dr. Nathan Price (01:12:40) – Yeah, we haven’t done that yet, but it’s going to be really important. The one area that we have looked at, and it’s a very important one, so phosphatidylcholine, I mentioned right? We think that’s really important for brain health and the model bears that out, the nutrition data bears that out.

Dr. Kara Fitzgerald – I’ve got some right here. But yeah, go ahead.

Dr. Nathan Price – But, and there is a but here, if you have certain bacteria, and there’s like 30 different bacteria that are known about, they will actually eat phosphatidylcholine and they’ll turn it into trimethylamine. Now you’ll probably know this right? Because trimethylamine gets in your blood, your liver turns it into TMAO (trimethylamine N-oxide). TMAO is a risk factor for cardiovascular disease. So, you could be pounding a supplement or eating lots of eggs, you’re trying to get your phosphatidylcholine up to your brain, which is a very smart, good thing to do, but if you actually have the wrong species of bacteria, you’re getting a different compound and that’s not good.

Dr. Nathan Price – Some of the ways you can do, you can monitor for that. I definitely recommend monitoring TMAO periodically, especially if you’re taking phosphatidylcholine, or something like that. I’m going to get mine measured again in a couple of weeks just to look for that. And then you can see if it’s in your microbiome and find ways that you might then try to shift that away. One of the things that I’d love to get into the twins and into some of the things we do with clinicians is to have a streamlined approach that’s monitoring for that, along with ways that you could really go about trying to remedy that. So that gets into an integrated approach.

Dr. Nathan Price – And it is important to think about because the microbiome- Every single thing you take into your body, whether it’s a supplement, food, or a drug, can get modified by the microbiome. And there was a great Cell paper a couple of years ago.

Dr. Nathan Price -So about 13% of drugs are metabolized away by the microbiome. And it’s a different 13% for different people. It depends on your microbiome. And they did this really deep, deep dive. So that means you could be on a clinical trial or just on a drug from your physician and you’re on something totally different. And you don’t know that because the microbiome is two black blocks. So that’s why when we say the microbiome is so important for health, it really is. And the depth that we have now compared to when we started Arivale nine years ago, radically better.

Dr. Nathan Price – And microbiomes in five years are going to be radically better than they are now. So, we’re learning, but a lot of this has become so actionable now, and I really think anyone that’s not paying attention to the microbiome is doing their patients a disservice at this point because it’s a critical factor to so many things.

Dr. Kara Fitzgerald – Let me just ask you this, let me go back to TMAO. Bob Rountree always talks about it as being a surrogate marker of choline insufficiency. So if you’ve got a bunch of TMAO, your choline in circulation is probably low because it’s being commandeered by the microbiome. You could actually look at that with your data set. You could go dive right into that. And answer Bob’s question. He brings this up all the time. We were just talking about this a little while ago. But anyway.

Dr. Nathan Price – One quick aside. That is the beauty of these really dense data sets. The kind we build at Arivale. It’s exactly this. And usually you say, “Oh, okay, I’ve got to go raise money. I’ve got to go do a clinical trial. I’ve got to go measure.” So as long as you’re doing these smaller data- But when you have something like what we had in the Arivale data set, you can literally know that by tomorrow.

Dr. Nathan Price – You can query it. Yeah.

Dr. Nathan Price – You can go query it. That’s why it was the most fun project that I ever did by a million miles, because you could just ask the question. I’ll give one aside, and then I want to come back to your question.

Dr. Nathan Price  – So the big effect on statins, for example. This is work, again, with Sean Gibbons at ISB. We took the Arivale data, because tons of people are on statins and we have their microbiomes, we have all this information, and we looked. So, we take microbiomes, we just cluster them into four groups, just data driven, and then analyze statin results for those different groups. And it turns out that if you have a microbiome in this group that’s high in Bacteroides, those people get double the lowering of LDL cholesterol on the same dosage of statin.

Dr. Kara Fitzgerald – Amazing.

Dr. Nathan Price – Double the effect. Now, the other side is that the downside of statins, or one of them, is that you get a nearly 10% increase in the rate of diabetes. Well, our study also has all the diabetes markers, right? We have hemoglobin A1 C and fasted glucose. So, we looked at the same influence of the microbiome, and in two of the four groups, you get a significant jump up in the diabetes markers. But in two of them they’re not statistically different at all. So, you can segment by the microbiome, people who are at risk for potentially transitioning to diabetes from those that aren’t that.

Dr. Kara Fitzgerald – Statin related diabetes. Wow.

Dr. Nathan Price – And see who was probably going to be the most efficacious. Unfortunately, there is an overlap between efficacious and having the diabetes side effect, so there’s not like one area that is overwhelmingly the answer.

Dr. Kara Fitzgerald – But you could go into it with your eyes open.

Dr. Nathan Price – You can. And you can understand it. And that’s just finding it, right? Now, we might be able by diving in, to really understand what those transformations are and optimize it for somebody.

Dr. Kara Fitzgerald – Yeah. So, what do we do now? How do we answer that question? How do we know? What do we look at in the microbiome to determine… It’s interesting. I have a patient whose calcium score just came back and it’s over 1500. So, she’s at really high risk. I mean, she’s going to have to be medically managed for that, in part, and maybe other things. But how do I discern whether she’s going to be a favorable responder or if she’s going to develop diabetes? Could I actually obtain that information from a stool test?

Dr. Nathan Price – Yeah. I mean, I think the best way… I mean, yeah, you can do it… Yeah. We’ve got to get that on the market to make it easy. If you have a, as I assume most doctors have an in-house microbiome computational person that can …

Dr. Kara Fitzgerald – Crunch some numbers for us, yeah, yeah.

Dr. Nathan Price – Yeah. Exactly. It’s totally easy. This is one of the reasons when I moved to Thorne and thought, I’ve got to get more of these things out in the market to make it easy for people to do this stuff.

Dr. Nathan Price – So, we can develop that. ISB did patent that, so they are trying to license this out to get a commercial partner to build this into a tool for doctors. So you can do that. Of course, the way to do it right now is to monitor for those diabetes markers. I think anyone on a statin you would watch for that. And then in the microbiome, you could look for this high abundance of Bacteroides, some of the features that are- And that’s not so hard to see and so you could look for that and if it looks like they’re in that clade, then that might be a reason to say, okay, well the microbiome might be partially driving this and then you could look into diets, certain fibers, and so forth to try to shift to a different microbiome and then update. I think there would be a fair amount of trial and error at this point, in terms- But you know, you can try interventions that are very you know-

Dr. Kara Fitzgerald  – It’s a creative way to look at a stool test that most of us in functional medicine are getting. All right, I’m going to circle back to TMAO again. Is this a surrogate- So, I talked about it being, or Bob is the one who suggested it as a surrogate marker of choline deficiency, so it’s being hogged by the microbiome. Is it a surrogate marker of dysbiosis also? Are the players who are banging out the TMAO, are they dysbiotic players?

Dr. Nathan Price – They are. They are, certainly. I don’t know if I would go so far as to say- I mean, they are dysbiotic in the sense that they’re making TMAO.

Dr. Kara Fitzgerald – TMAO. Right.

Dr. Nathan Price – And so I’m not I’m not exactly sure how far I would push that in any of their particular cases. They are definitely dysbiotic in the sense that you want them gone. And as far as I know, there’s no positive benefit to them. It’s not like when you’re getting rid of those bacteria, as far as I understand the science today, you can get rid of them. A score of zero is the best score to have on them. So, it’s not like they’re doing all these positive things and then there’s a side effect of TMAO. As far as I know, those things can all be filled in by other bacteria that won’t make that substance.

Dr. Kara Fitzgerald – That’s really interesting. Okay. And your stool test actually tracks all those TMAO players. Are you?

Dr. Nathan Price – The Thorne test does not do that in as much detail as I would like it to yet.

Dr. Kara Fitzgerald – Okay, and who are? Can you just name a couple that I might be familiar with? The listeners might be familiar. No pressure.

Dr. Nathan Price – We had a great version of it at Arivale. I’m not sure who else’s test would do better on that, honestly. I’m not aware of one that that does it really well. We built that at Arivale when I was there. It was like one of the very first things we did. We will have it on the next version at Thorne because I moved here and I want it on there. And so, that that’s coming out.

Dr. Kara Fitzgerald – We’ll stay tuned. Yeah. I mean, in the meantime, we’ll measure TMAO. There was a paper that came out recently that you were associated with. I know you weren’t an author on it, but you were associated with it. And I know it’s born out of work that you’ve been involved with forever. It’s A Remotely Coached Multimodal Lifestyle Intervention for Alzheimer’s Disease Ameliorates Functional and Cognitive Outcomes. This just came out. So, you’re looking carefully at, I’m assuming that they were using the digital- I’m wondering if they were using the digital twin model, but I want to just anchor that back to your book where there’s a pretty moving chapter that Lee Hood wrote about his wife and her descent into Alzheimer’s. It’s really moving. And then, obviously you guys go into, you know, extensively your thoughts on what we need to do to preserve cognition as we’re aging. But anyway, so tie that all together. This paper, is this using the digital twin, and just, you know, appreciate the chapters in the book.

Dr. Nathan Price – Yeah. So, the paper is not using the digital twin and that’s partly- It’s just the timing of these things. I had a pretty big role in initiating and launching the work that led to that trial, but then when I moved from ISB to Thorne I was less involved in the details of that trial. I think I’m listed as part of one of the consortium members or something like that. But Jared Roach really led out that trial. And that trial tried to keep things very simple. So it was-

Dr. Nathan Price – And it became remote during Covid. And at that point I had moved to New York, I think, well, during this period. So, what they did was remote health coaching, dietary and lifestyle advice, and brain training, you know, cognitive exercises, basically. Those things were used and what they were able to show was that very in the spirit of FINGER (trial), and the more recent The Four Winds trial, and things like this, basically shows that you get more benefit from these lifestyle interventions than any known pharmacological agent.

Dr. Nathan Price – And it showed an ability to- But it would still just slow the rate of decline in those cases. It was almost flat, the group that was treated, but it was slightly down. And then there was the untreated group that came down more. So again, just showing that dementia is lifestyle modifiable. The digital twin stuff was- And what’s in that chapter of the book, you know, so there’s the lead story, then the next chapter was really mostly about the kind of work that we did on the digital twin models after I moved to Thorne. That’s the area where we really got into that. It would be great if that trial were the trial of the digital twins, but we were actually building the digital twin model contemporaneously, starting with that trial, in fact, we started the trial earlier. Because the trial initially was going to be a straight up test of the Arivale program on dementia.

Dr. Nathan Price – So it was kept to the same set of measurements that we were using in Arivale and the coaches. Jennifer Lovejoy was very involved in that back then as well. And so that was the way that that was set up and I think it came out as another example that multimodal works, even if done remotely, the health coaching just makes a difference. And it gets into one of my real pet peeve topics, which is, that for so long, especially when genetics first started coming out, people would repeat over and over again, don’t go find out about your genetics because you’ll learn you have high risk for Alzheimer’s and there’s nothing you can do. And that’s such a lie. What was always meant by that is there is no drug that’s approved that has any sort of useful treatment for Alzheimer’s, which is true. But for prevention you can do so much. And for listeners that are interested, I did write this piece for the LA times a few months ago arguing that the return on investment or the focus on treatment over prevention of Alzheimer’s has been really a disaster because we’ve spent hundreds of billions of dollars, at least, especially on anti-amyloid therapies, and got almost nothing in return.

Dr. Nathan Price  – And yet prevention is in a totally different universe. And I do want people just to think about this, maybe it’s obvious if you do. Once you’ve lost your neurons and synapses, the notion that a small molecule is going to regrow them, bring them back – totally fanciful, as far as I can tell. I don’t know what mechanism would possibly do that. But prevention, keeping those neurons from dying in the first place. Way easier. Much more doable. Very possible problem. And of course, we’ve all known this since we were three years old. This is the story of Humpty Dumpty. So, it’s like, once it’s broken, hard to fix. Keeping it from breaking is much, much more reasonable. And so, I think that’s the thing, you know, so coming back to that genetics, find out. In other words, it’s not, “Don’t find out your Alzheimer’s, there’s nothing you can do.”

Dr. Nathan Price – It’s “Find out because there’s so much you can do on prevention.” And some of these are so easy; vitamin D, phosphatidylcholine, omega-3s, DHA, phosphatidylserine, exercise, oxygenation to your brain is massively huge, get out, run, jump around, lift weights. All this stuff makes a huge, huge difference to your brain health over time. And so that’s one of the things I think is such an important message, just to get out there is: Alzheimer’s is not fatalistic. There’s not an infinite amount of room to push it off, especially if you have the bad genetics. But honestly if you push it off, I mean, there’s other things…

Dr. Nathan Price – I was listening to these lectures on genome writing from Flagship Pioneering recently. An old colleague from grad school days, Geoffrey von Maltzahn, was talking about this and some other people. But as that gets better, in our lifetimes, we’re probably going to be able to rewrite you’re APOE4 and we can probably get rid of it and we’re off to sea. So you want to be doing all these things so you extend your time period because then your envelope could change radically and you could get an APO2 and all of a sudden Alzheimer’s is not going to happen until you’re 100 or more. We all know that there’s that possibility as we get on to these exponentially rising improvements.

Dr. Kara Fitzgerald – Boy, we are at an extraordinary time in science and medicine. God. So glad we had this conversation. Thank you. I have a I have a ton more questions. I will just have to circle back.

Dr. Nathan Price – Any time. Any time

Dr. Kara Fitzgerald – Thank you so much for your time today.

Dr. Nathan Price  – Yeah. Thank you, Kara. Really, really great to be with you. I really appreciate it.

Nathan D. Price, Chief Scientific Officer, Thorne HealthTech

Professor (on leave), Institute for Systems Biology

Dr. Nathan Price is Chief Scientific Officer of Thorne HealthTech and author of The Age of Scientific Wellness. Previously he was CEO of Onegevity, an AI health intelligence company that merged with Thorne. In 2019, he was named as one of the 10 Emerging Leaders in Health and Medicine by the National Academy of Medicine, and in 2021 he was appointed to the Board on Life Sciences of the National Academies of Sciences, Engineering, and Medicine. He spent much of his earlier career as Professor and Associate Director of the Institute for Systems Biology (now on leave), co-director with biotechnology pioneer Lee Hood of the Hood-Price Lab for Systems Biomedicine and is Affiliate Faculty at the University of Washington in Bioengineering and Computer Science & Engineering. He is a Camille Dreyfus Teacher-Scholar, received the 2016 Grace A. Goldsmith award for his work pioneering ‘scientific wellness’, was a co-founder of Arivale, and received a Healthy Longevity Catalyst Award from the National Academy of Medicine in 2020. He has co-authored more than 200 peer-reviewed scientific publications and given over 200 talks and keynotes. He also served as Chair of the NIH Study Section on Modeling and Analysis of Biological Systems (MABS) and is a Fellow of the American Institute for Biological and Medical Engineering.

 

Public Contact Info

nprice@thorne.com

https://www.linkedin.com/in/nathandprice/

X(Twitter): @ISBNathanPrice

Show Notes

Dr. Nathan Price

Thorne HealthTech

The Age of Scientific Wellness by Leroy Hood, MD, PhD and Nathan Price, PhD

Onegevity

National Academy of Medicine

National Academies of Sciences, Engineering and Medicine

Institute for Systems Biology

Hood-Price Lab for Systems Biomedicine

Arivale

Healthy Longevity Catalyst Award

American Institute for Biological and Medical Engineering

Pioneer 100 Study – A wellness study of 108 individuals using personal, dense, dynamic data clouds

Article in Science: ‘Scientific wellness’ study—and a famed biologist’s spinoff company—divide researchers

Moshe Szyf

Longitudinal Study – Multi-omic Biological Age Estimation and Its Correlation with Wellness and Disease Phenotypes

Dr. Fitzgerald’s Study: Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial

Morgan Levine, PhD

Steve Horvath, PhD, ScD

An epigenetic biomarker of aging for lifespan and healthspan

Thorne Biological Age Health Panel

Study: Gut microbiome pattern reflects healthy ageing and predicts survival in humans

MedAware AI-powered medication safety monitoring platform

Robert Rountree, MD

Case Studies in Integrative and Functional Medicine by Kara N. Fitzgerald

Thorne NanoDrop

Paper: A Remotely Coached Multimodal Lifestyle Intervention for Alzheimer’s Disease Ameliorates Functional and Cognitive Outcomes

Jared Roach

The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) trial

Precision Medicine Approach to Alzheimer’s Disease: Successful Pilot Project

LA Times Article: Opinion: New Alzheimer’s drugs are costly and controversial. Are we going about this all wrong?

DNAm PhenoAge Test – An epigenetic biomarker of aging for lifespan and healthspan

 

PRACTICE BETTER: Start your free trial and save 20% for 4 months on any paid plan with code KF20

DrKF Resources

NFFM Sponsors

Younger You Daily Supplements are Now Here!

What could be more convenient than having your daily supplements all pre-portioned in one pouch? Choose your level to get the combination of supplements that’s right from you. Monthly subscription available.

(note you’ll be leaving www.drkarafitzgerald.com to go to www.vitaboom.com to complete your purchase)

Exit mobile version