The Age Of Scientific Wellness: Bringing In More Precision And Scientific Rigor To Modern Medicine With Dr. Nathan Price, Thorne HealthTech

BPU 12 | Scientific Wellness

There is so much that's happening now in the field of scientific wellness. There are so many bright and incredible people that are on this train, building all the different pieces of it. It's an exciting space to watch as this all emerges. In this episode we have a conversation with Dr. Nathan Price, the Chief Scientific Officer of Thorne HealthTech. He was previously Associate Director at the Institute of Systems Biology. Along with the founder of the ISB he has a new book called The Age of Scientific Wellness. We talk about how to intervene to achieve wellness without having to face the challenge of the relatively high toxicity profiles of current therapies. We also touch base on an approach to finding out which molecules or biomarkers are most important for identifying chronic diseases early without having to run a 20 year study and why it is important to focus on what patients care most about right now. The conversation then evolves in to a discussion about how to handle the complexity of decision that rapidly increases when you start considering things like genomic data. Nathan also explains how he has overcome interpersonal challenges in the past and the importance of looking after your wellness. He also highlights what Thorne Health Tech has been doing to take the 'ick' factor out of the personal testing of one's microbiome.

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The Age Of Scientific Wellness: Bringing In More Precision And Scientific Rigor To Modern Medicine With Dr. Nathan Price, Thorne HealthTech

In this episode, we have Dr. Nathan Price. He's the Chief Scientific Officer of Thorne HealthTech, which we will talk a bit about in the beginning here. He's also the author of The Age of Scientific Wellness. In 2019, he was named one of the ten emerging leaders in health and medicine by the National Academy of Medicine. In 2021, he was appointed to the Board on Life Sciences and the National Academy of Sciences, Engineering and Medicine.

Previously, Dr. Price was the CEO of Onegevity, an AI health intelligence company that merged with Thorne. Prior to that, he served for a decade as a Professor and Associate Director of the Institute for Systems Biology where he was the co-director with the biotechnology pioneer, Lee Hood, as part of the Hood-Price Lab for Systems Biomedicine. He is an affiliate faculty at the University of Washington in Bioengineering and Computer Science. He is a Camille Dreyfus Teacher-Scholar. In 2016, he received the Grace A. Goldsmith Award for his work pioneering scientific wellness.

He was a Cofounder of Arivale. He received the Healthy Longevity Catalyst Award from the National Academy of Medicine. He has co-authored more than 200 peer-reviewed scientific publications and given over 200 talks and keynotes. He's also served as a chair of the NIH Study Section on Modeling Analysis of Biological Systems. He's also been on many different company boards and a whole long list of awards but we won't go through all that so we can get right to the discussion. Welcome, Nathan. Thank you for coming on.

Thanks so much, Scott. It's great to be with you.

I always like to start with a more personal question. You're sitting in a nice office. Is there something on the desk or something in the room around you that you can describe for the audience?

 
 

We have moved into these new offices. We have a few things that are in here lying around but one that I like is this picture that we have of the whole team when we rang the Nasdaq bell. That was the culmination of an incredible amount of work to bring Thorne HealthTech as a public company onto the Nasdaq. It was a fun time to hang out with people that you're on a mission with and on a journey with and try to build something that we hope will have lasting value in society. We will get into what we're trying to do with all this and this vision for scientific wellness and so forth. That's a fun reminder of a happy day and a lot of great people.

That's a significant achievement to get to that point. There's still more to do but that is quite remarkable.

You don't get to do it very often. It's such a quintessential New York thing. I moved to New York. It's like, "We have rung the Nasdaq bell. We can look out in the back window at Central Park. It's the New York thing." It's great.

What excites you the most about what you're doing?

What I'm most excited about is what I see as a major transformation in how we think about healthcare as a society that we call scientific wellness that Lee Hood and I have done. You mentioned the book The Age of Scientific Wellness where we get into this a lot. It's the notion that as we think about how healthcare has been defined, it was set up scientifically in the 1900s with the Abraham Flexner Report and so forth. It set out as a response to infectious diseases that we're all dying from and it was spectacularly successful. If you look at all the stuff we died from in the early 1900s, we don't even think about them.

It's amazing. It's an incredible achievement but if you fast forward and look at the issues that we have with chronic disease, Alzheimer's and diabetes, it's rampant. The way that we took that old approach of, "Find the pathogen. Kill it," is we turned that into, "Find the target. Drug it," especially with single drug targets and so forth. As we know, the whole pharma industry is dealing with this. There are diminishing returns that have been happening. We have not eradicated or put into the dustbin of history any of these chronic diseases yet.

One of the issues that we have and that I'm most excited about is trying to build what we call a scientific wellness industry that's focused more on, "How do I quantify and understand health, understand what the earliest transition stages toward disease are, stop them before they get started, try to extend health span and have a system that is focused on maintaining and extending health, healthy aging and all those things, not only on this care of disease?" What I'm excited about is trying to build as much of the foundational science to bring wellness to that same level of scientific rigor that we have had in trying to understand disease processes for so long.

I want to go a bit later into the transition from wellness into disease but I wanted to expand a bit about what you said because what you pointed out there was a very interesting point. In a way, we have shifted from infectious diseases to trying to take that same mental model and put it into treating chronic diseases. One thing that also struck my mind when you said that and I would like to see hear your opinion on this is there's this natural asymptote.

As we get into chronic diseases, even cancer, for example, you get to a certain point that if a new drug comes in, you have to do it on the existing therapy. You have this plateau in the new drugs because it becomes increasingly harder to show efficacy. You're only treating stage-four cancer. You're not treating the early stages anymore with the new drugs. That may not be the case but that happens in asthma as well. There are pretty good drugs but that means still there are 20% of people who aren't getting better with those pretty good drugs. Do you think that this shift to wellness will upset that and impact all that?

I do. I wouldn't be dedicating my career to it if I didn't. I want to be careful when I say this in the sense that I don't want to cast aspersions on that. There are a lot of valuable and great things that people are doing. You look broadly at the success. For example, Nick Schork published a paper in Nature in 2015 called Time for One-Person Trials. In there, he went through the number needed to treat these drugs in terms of having an observable benefit for a person. It turns out of the top ten selling drugs in the United States, you get a number back that says that it benefits about 10% of the people.

The title of the famous slide that came out of this was imprecision medicine. This is a big impetus for the precision medicine movement, the right drug, the right time and the right patient. While that addresses part of the issue, we have a much more fundamental issue. As long as you're thinking about late-stage disease and trying to build a drug for it, which is what our pharma industry has set up to and it's a big machine to do that extremely well, we're missing the boat on a lot of these.

The most obvious example to me is Alzheimer's disease. In Alzheimer's disease, especially as you get into the late stages, your neurons are dying. You've lost a bunch of neurons and synapses. The corollary of that is you've lost a lot of your memories and your cognitive ability. Nobody knows how to regrow that and bring that back. There's no way in the world that a single-molecule drug will restore a person's brain. There's no chance of that. You could imagine it with some futuristic mapping of the brain, stem cells and regrowth. You could imagine some sci-fi future where you can do that but now, there are many things that you can do to prevent neuron loss.

Prevention of Alzheimer's makes tons of sense. The only big clinical trial that has been successful was the FINGER study that showed lifestyle, blood measure, supplementation, exercise and things of this nature and the ability to prevent or delay the onset of dementia. We can get into drugs more specifically. We have one that was approved but even the very best drugs for Alzheimer's and none of them are very good, only slow the rate of decline a bit. If you gear yourself to that mindset, it's so obvious that what we have to do is to stop these things before they get going because once you have all that damage and loss, there's no way that the paradigm of giving a drug for that issue is going to be curative.

This prevention or interception concept has been growing. You often run into it, particularly if you talk to traditional industries. They say, "There's no regulatory framework for that. How are we going to get a drug approved for that? There's no business model for it." I don't know what's your take. You think there is.

What you're bringing up is an important point. Let's talk about a few of those challenges. One of the things is that we default very strongly to, "There has to be a drug for that." Especially if you're thinking about side effect profiles, you can have a drug that has negative side effects when you're giving it into a life-threatening situation. You can never do such a thing if you're talking about a person that's overall health. You give chemotherapy to someone dying of cancer. You never give it to a regular person. That would be insane.

That's why a lot of the critics of scientific wellness, especially in the early days, often came out of oncology. I get it. If those are the therapies and the interventions, you don't give them early. I would agree but there are a number of pieces that come from that. Let's take that first. Interventions need to be safe. That is a big reason why I'm at Thorne HealthTech. I do think that the precision use of natural products is likely to be part of the solution because they have an incredible safety profile. You use things that you can leverage over decades. You should be able to nudge systems in ways that are safe enough to use for people. That's one thing.

Let's get to the second point, which is in terms of business model and proof of concept. With a drug, because they're so high priced, typically, you can get an economic model that makes sense for you to do this huge development process, massive clinical trials and all those things that we go through to try to come up with a good drug. It is very hard to justify doing that in a wellness space, especially if what you're thinking about is, "I've got to do a longitudinal study and recruit. I don't even know who's going to get the disease. I can enrich by genetics but I've got to watch them for decades. It's going to cost a fortune. There's no way to get there." That's a big problem.

I'm going to come to solutions in a second because I do think there are some answers here. The third big problem is this. Let's say I give you a scientific wellness type of treatment to prevent you from getting Alzheimer's and then you don't get Alzheimer's. It's a counterfactual. You don't know if you are going to get it. You can prove it in a population. As a population, you could go and prove that people going through this get it at half the rate but it's not like you can prove it exactly for a person.

Those are big fundamental issues. That's the reason that most people have shied away from this space and continued around the typical path. Given that those are big issues, I'm going to tell you some of the things that make this possible. The first thing is this. The whole reason that Lee and I got focused a lot on what we call scientific wellness was in part a response to those problems. In other words, we thought, "There's no way that you can fund all these huge longitudinal studies for every disease separately and so forth."

What that meant is that to get the data that you need in wellness, what you have to be able to do is learn enough from the data that you can get to make a meaningful impact on a person's health and life. If you can show that by getting this data, you can personalize interventions in such a way that it helps optimize a person's energy, well-being, sleep or something that they can feel. As a byproduct, you start building this longitudinal information that you can then use to study early transitions to disease.

That's partly why we're working so hard at building what we call the scientific wellness industry. It has to be its economic model and work. You generate the data clouds. It leads you to these preventive models as a byproduct of doing that well for people. That's the first big thing. The second big thing that we realized as we went through this is that the model that I had in my head initially was what we talked about, "We got to recruit 100,000 people or more and have them go through a program with us for a couple of decades. We will monitor and be able to see what the transitions look like."

That's a very long way to do it. I talked about why it led us to scientific wellness as a byproduct. That can't be the focus. You've got to be doing this other thing that gives you that other piece of the byproduct. One of the other elements that we have learned or that dawned on me one day is we don't know who's going to get these diseases in advance but we have good genetic signals for the disposition of diseases. Polygenic risk scores have gotten much better. We could go off on a tangent on that if you want to because I love that topic.

What it said is, "I can already take the people for whom we have these dense dynamic data clouds, metabolomes, proteomes, microbiomes and thousands of measurements that we do on people. I can segment them into groups based on those polygenic risk scores of who's likely to get this disease in the future and who's not. I can ask immediately what's different in all of those data types between the people who are at high genetic risk for a disease or low."

Here's the thing that comes out of this that is fascinating. We published a big paper on this in the Proceedings of the National Academy of Sciences a couple of years ago. What it showed was if you take something like coronary artery disease, we're looking at people who don't have coronary artery disease but people who are at high risk versus low risk. We look at the concentration of proteins in their blood and what's different. It turns out there's only 1 of the 400 or so we looked at and it's PCSK9. What's the biggest blockbuster drug in the last few years in that space? Anti-PCSK9.

For asthma, we did the same thing. There's only one, IL33. We look up and lo and behold, there are four drug companies at the time that were developing therapies at various stages with IL33 as the target. I could go on for a bunch of them but when you're thinking in the traditional model of late-stage case-control, you do omics data. I've done a ton of it. I have 100 papers on this stuff too. We do all this stuff for a long time. You go in and look at that. What you find is that there are hundreds of differentially expressed genes or proteins.

You're trying to sort out three things. What's causing this disease? What are the consequences or in other words, the negative perturbation and all the things that happen downstream? What are the compensatory mechanisms or the good things the body is doing to try to combat the problem that has been introduced? Those are all mixed into the same bag. We have to try to sort it out. It's messy but when you look super early, the signals are sparse. They're heavily enriched for being causal.

All of a sudden, we start seeing these benefits. You think about scientific wellness, you focus on how to understand the health state and you see the early transitions and a movie of the whole process from beginning to end instead of only looking at the messy end. That is incredibly valuable. I only thought of this when we started the process. I didn't know. We had tons of people tell us, "This is going to be a waste of time because there's no disease. Who cares?" I feel so radically the opposite that we have spent these years and published so many papers on it. It's incredibly informative.

There's a lot we could dig into there but first, I'm going to be right off that point. What do you think gave you the faith that this is going to happen? People were saying no but you said, "This is going to work." You see, "It comes through." It's very interesting because I spend a lot of time helping people to design big complex projects. They're often very ambitious. You get this all the time, "That's too difficult. We need to do something simpler." When you have that big goal, most of the time something pops up as you go forward that says, "We can reach that goal." I would like to hear your take on what kept you going.

I'm a pretty optimistic and driven person in general. I was excited about that but I also want to give a lot of credit here to Lee Hood. For people that don't know, Lee has this incredible history in science. He invented automated DNA sequencing. He won the Lasker Prize for the discovery of the MHC complex in immunology. He has this history of going against the grain and being right many times. This was my first big time when I was going in a different direction. Everyone was telling me, "This doesn't make sense. It's a waste of time." We're going out and doing this.

It was an incredible support to be doing it with Lee because Lee has seen this thing so many times. It was interesting in the conversations with him. He almost doesn't care about the topic unless he's hearing a bunch of people telling him, "You're on the wrong path. You're not on an interesting path." I developed a wonderful friendship with Lee over the years. He has been an incredible mentor to me in my early days. It was fun. We had this sense of being on a mission on that. Having more opposition in some ways made it a little bit better. We did have a lot of it.

I was going forth as strongly as I could but inside, I had some trepidation as well. You're like, "Maybe they're going to be right. When we open the box, it is going to be a huge waste of time." What I have been so surprised by as we get into the book is how much we were able to learn. To give a sense of that too, we did an analysis of our lab at one point. We were running a pretty big lab. We had $7 million a year in funding, which for an academic lab is a big lab.

When we were doing that, we did an analysis though of what it came in on different topics because we had a lot of our traditional and what people were citing on the papers that came out of it. Scientific wellness was 3% of our funding. We had some foundations like the Robert Wood Johnson Foundation and the Murdock Foundation that supported us. Federal grants were not interested in this as a topic but 55% of the work of what people cared about came out of that.

We had this whole calculation we did, "What money is coming in? What will be funded? What do people care about when it comes out?" The big standout was the vast majority of our big Nature journal papers and flagship papers were almost all based around what we did with scientific wellness, even though that was all funded either privately or from some philanthropy. That was very interesting. It became much more accepted. That's why we wrote the book and talk about it.

We get a huge interest in it inbound all the time. It even led to Thorne reaching out to me and Paul Jacobson saying, "We have a public scientific wellness company on the Nasdaq. We are starting to build that out at real scale." The world is starting to turn a lot more. We're even looking at different bodies that would have been dismissive of the concept of studying wellness that are engaged in thinking about it deeply. It has been an incredible sea change since we started this. It has been a long time.

It's a great illustration of foundations or nonprofits funding where they should be working. It is sometimes pushing that bold limit because you see it. The impact they got from 5% of your funding is phenomenal. It outstripped the rest of the 95% of your funding in terms of impact.

In terms of impact and citations, the scientific wellness funding had radically higher returns than anything else we did during that span.

I see this. Traditionally, disease foundations funded it and had a panel but there's a push to get them more engaged in pushing and helping to drive. There was a New England Journal article in 2017 that went over this, going with the Ivacaftor story of cystic fibrosis. The Cystic Fibrosis Foundation pushed it and then that got FDA approval in four years, which is another remarkable story along this line.

I wanted to wind back a bit because when you talked about wellness and looking at energy, fatigue or what patients care about, that also tails into the whole patient-centered drug development or patient-centered care idea. That's a very fascinating aspect of it because sometimes there's a disconnect between the end of what the people developing the therapy or the clinicians want and what matters to the patients, which are things like energy. I see what you're doing is the potential coupling of those two. That gives you some traction to get the data that then maybe can justify the rest and bring everybody else along. Is that the right way to think about it?

That is the right way to think about it. One of the elements that we're interested in is taking a lot of these omics data and building health scores off of them that are relevant to a person's life. They can relate to their metabolic health or cardiac health, inflammation or whatever it is. By tying those things together and giving them actual information, we can then start to learn a lot from those thousands of measurements that are undergirding those. That does get into the space of having to go through the hard work of getting those tests validated and connected to where you can say meaningful things about a person's health but there are a lot of these informative things.

I'll give you an example of a clinical marker that's widely used. Something came out of these studies. Let's take something like LDL cholesterol. LDL cholesterol is measured in millions of people across the country. People are given statins for these. Typically, statins are one of the most successful drugs ever. One of the interesting things is that we looked at people going through a scientific wellness program and whether or not they were able to successfully lower their LDL cholesterol by lifestyle intervention. Let me preface this. You go into the healthcare system. That gets measured. You get your statin.

One of the questions we asked though was looking at how predictable LDL cholesterol in the blood is from your genome. It turns out that your genome predicts it. At the time, it was about 11% of the variants, which doesn't sound like a lot but it was enough to move you from the top of the range to the bottom of the range from the clinical band. That polygenic risk score is twice as strong as it was back then but we will take it at the time.

We looked at it and then we bucketed people into five buckets based on where they were in terms of low risk to high risk. We utilized that information to then do an evaluation of who was able to lower their LDL cholesterol. What came out was if you had high LDL cholesterol because your genome predicted, we saw no ability for those individuals to lower their LDL cholesterol by lifestyle. You could hammer it with a statin but you couldn't lower it by lifestyle. If you're in the low group, you could. That's 40% of people at the top. We're talking about millions of people.

I'm excited about this. It needs to be pushed into healthcare all over the place. The variable that mattered was what was the delta or the difference between the actual measurement and the predicted measurement from the genome. If there's a big gap, it's pretty easy to move. If there's not a gap, it's hard. Imagine that. It's true also for HDL cholesterol and hemoglobin A1C. You can go down the line and look at it for all blood measures. Some of them will be strongly genetically predicted. Some of them won't. I'll come back to that.

When we look at that then when you go to your doctor, none of that information is used at all and yet one of the most obvious easy things to do with genomics that's very impactful is to take every blood measure that you have, look at the gap and say, "Here are all the things where you could make a real difference pretty easily. These are the things that are very unlikely to change for you without some drug intervention." You get that right off the bat.

The second corollary to that, which is a little bit different, is that maybe the standard clinical range doesn't make any sense to you. For example, you can have genetics that is associated with how long of a residence time your red blood cells have. Let's say my red blood cells circulate for 110 days and yours for 130 days. 120 is average. Let's say that. That would mean that if you had a high hemoglobin A1C score, that would be less worrisome than if I did because hemoglobin A1C is the accumulation of glycosylation over time onto your hemoglobin. If yours are around 130 days and mine are around 110, we should normalize for that because it doesn't make any sense to compare those as the same number. There are many cases like this.

I want to make one more point. I said, "Some of these things will be genomically predicted and some won't be. We will see," but our genomic predictions are getting better all the time. I want to give the example of height. For people that are outside this field, this is a fascinating example. We all know that height is heritable. If you have short parents, you're probably short. If you have tall parents, you're probably tall. In the early days, they tried to find out the gene or set of genes that control height. They couldn't find any.

This was a big mystery at the time, "Why are there no genes for height? It's non-predictable." As we started ramping up these huge genomic studies like the UK Biobank and these different things, we have been able to get much better scores. It turns out that height is the most predictable of all the polygenic risk scores that I've seen. The correlation is 0.61%, which is huge. It was the R2. I'm not 100% sure. That's what it was. How many genetic variants does it take to do that prediction? 180,000.

How many of these things are predictable? Even if we say something isn't predictable from genetics, eventually it might be. We get into questions of heritability and so forth but the notion that we don't use the genome very extensively in medicine, to me, is crazy. It used to be that's the absolute wisdom. There's nothing you can say but there are tons you can say even from our work. If you take everyone else's work, it's radically more.

There's another dynamic as well. I know this from being on a lot of projects. We're working on multi-omic approaches. Even in that project, people who were in it who were more clinically oriented said, "I don't understand this. How am I going to use this?" There's resistance to learning because they're overwhelmed as it is. There's a natural barrier to practice. There's one thing I always think is important. Healthcare innovation is a multi-stakeholder problem. The patients need to be accepting. The regulators, the researchers, the industry and also the clinicians need to be able to use it because you can have the best science in the world. If they don't like it and they don't understand it, it's not going to get put into practice. That's a bigger challenge.

That's partly the reason why I made the jump from academia into the industry. I still do some things with ISB in publishing papers and so forth, which I love. The reason I did that is exactly the point you make. Too often, you could come up with something that's a good concept and nobody will use it. You have to coordinate all those pieces together to make these things happen.

One of the elements is that there's a lot of complexity to take the incorporation of genomics into medicine that we talked about. The onus then has to be on building up an industry that absorbs that complexity because that complexity cannot be funneled through the brain of a doctor or the brain of a patient alone. It's got to do that but this is also why as we're coming into the throes of the AI revolution, everybody else is obsessed with ChatGPT and all this stuff that all of us are doing. It's the fastest-growing platform ever. It's insane.

We have to leverage those tools so that we can take this complexity of the data. AI is going to be essential for us to understand biology deeply enough because it's incredibly complicated. Simplify or abstract away from that so you have actions you can take that will then steer you around these very negative outcomes. We all have friends or loved ones who we thought were doing pretty well and then all of a sudden, they're gone. We had a few of those in the last few years, which is shocking. You would like to be able to stop that from happening in as many people's lives as possible.

There is this convergent. A bunch of doctors come to a lecture. I show them data on whatever. There's no way that they go back the next day and start doing it with their patients. You have to build products and tools that easily plug into an ecosystem that deals with all those stakeholders. You have to be able to deal with that not only scientifically and practically but also economically. That always comes up. How do we sustainably do that? That's what I see as a lot of the next phase of my career. Having moved from my primary from ISB to Thorne HealthTech is about trying to play a role in that ecosystem to try to make more of these things more useful to as many people as possible.

Biology, as you pointed out, is extremely complex. We have taken the low-hanging fruit but AI will enable us to begin to work together to solve those problems practically. The practice of medicine is probably going to change radically. Physicians are going to have to begin to understand this a bit. The parallel is probably HIV. Infectious disease doctors were more about cultures and identifying bacteria. Suddenly, they're about the different side effects of the ten different drugs they have to give somebody. That's where medicine is probably going to some degree.

We're going to get a lot more detailed information in front of doctors as well. Some things over time will feel like they're safely automatable but a lot of what will happen is that you will be able to see the probabilities down different pathways a lot better. It will take it into account. You can imagine a tool where a doctor comes and says, "I'm looking at the following options for this patient." In the back end, there will be computations against that person's genome. How meaningful are the different blood measures for them? What's the likelihood that they will respond to different treatments and so forth?

We haven't released this yet but internally, we have spent the last few years building a detailed digital twin-based model of brain health, which makes these kinds of predictions about how long before a digital twin falls into dementia. It goes through interventions that can be done and the number of months or years of delay that you can get. They're highly personalized predictions. We've got to turn that into testing so that we can map that into patient space. It leverages about 930 papers at the last count and over 30 clinical trials and all the data that are available from those.

You start to get this detailed view that goes from the time scale of what's happening at a molecular time scale on the millisecond standpoint. It maps out over decades of life. We have this very cool ability that we developed jointly with our partners at EmbodyBio. We're going to be launching a bunch of stuff on that in 2024 so people can see that.

In essence, it's this whole category, which is becoming so much richer, of being able to take AIs to both do discovery and learn from all the data but also to do inference for people on the end of one level of what would be the most impactful for this person and make all that stuff much more visible. Biology is very complicated. We only partially understand it but it's getting a lot better, especially with the AI revolution that we're in the beginning stages of. The acceleration is going to be a lot faster than maybe a lot of us thought even a few years ago.

ChatGPT is a shock. It's impressive how good it is. I was talking to one of the people from Microsoft. He did point out though that if you were to ask it, "Give me these locations," that stuff is not better than the search engine. It will give you the wrong answer but that's not what the point of it is. The point is that it's understanding your question and putting it in the right form and shape.

As a language generator, it's amazing at being able to do that. The breadth of what you can ask it to do is incredible. There are still big blind spots there. An interesting one I saw was someone was asking to write a haiku poem. The language generation was quite good but it wasn't getting the right number of syllables. It was a person trying to explain to ChatGPT, "I need 5 syllables and then 7 syllables." They were going through and specifying what they wanted, which he failed at repeatedly over and over. It's not numerically literate yet.

With that said, I've seen some people that have gone on, "It can't do this or that." It's an insanely great achievement. It's mind-blowingly good. You can see those edges but those things are likely to get filled in. It's going to be unleashed on the internet soon. I have asked it to write an article on Alzheimer's disease. It spits it out and goes through the standard hypothesis, which I don't believe in. It's going away but it gives you the average of the text base it has learned.

You can say, "Write an article on Alzheimer's that's critical of the amyloid hypothesis." It gives you all that, "Write an article on Alzheimer's that's fundamentally more of a metabolic disease." I find it an incredible way to get insight into the average view represented in a huge bolus of the text of what people think of if I say the following statement. It's incredible.

It's like Wikipedia but better in a way. It's a bit more specific. You can dig in deeply.

Those tools will start revolutionizing healthcare for sure.

I was going to make it make a transition because what's impressive to me is that you have this vision and these ideas. You're doing exactly the whole premise of this show. We need leaders who are pushing beyond, "I'm going to write a paper and that's my career." I want to shift a bit, talk about your career and maybe say to you, "What was the lowest point of your career? How did you get through it?"

Probably the lowest points of my career without getting into too much detail were some interpersonal problems with a colleague who had become pretty aggressively negative with me and some members of my team. It became a toxic relationship at some point. Personality-wise, I like to get along with the people around me. I like to feel like we're all on the same boat moving together. I tend to be positively oriented. That's not an accident. I decided when I was depressed in middle school that I would change my outlook to try to look on the positive all the time. It's become a huge habit of mine.

When you asked me about the lowest point of my career, my immediate response is, "I don't understand the question." You have these out of day to day but that one was quite difficult. It was a big growing experience. It helped me to become stronger in terms of getting over that need, "Not everyone has to like me. If they don't like me, it's fine," and also learning to stand up for people that are under your umbrella, for example. We had some cases where there were things that I thought were aggressively bad toward students that were in my group. It's having to step up, play defender and be like, "I'm going to get into the muck and the disagreements that I dislike because I need to. This behavior has to stop or whatever it is."

The low points for me career-wise would be when there are issues that are interpersonal and that I feel are by and large so unnecessary in society. You can disagree vehemently pleasantly. You can't argue over ideas. I'm very happy to do that. That's probably the stuff that we're working through. In leadership positions, which I've had a number of, you deal with a lot of that stuff. It's interpersonal. I was also coming to the realization. I tend to look on the positive and believe the best of other people in general but I have learned through experience that what we all do ultimately is not always deserved. It's building to be slow to come to that conclusion.

It's a challenge because you want to make everybody happy but then you're leading a lab or helping others that come in conflict with that. You've got to learn to deal with that.

Being a people pleaser or always trying to make other people happy will drive you insane. Shedding is a very important part of growing up and becoming a happy and healthy human being. I'll share one thing about my early pathology. I became deputy editor-in-chief of this journal early on in my career. I was a second year. I was a little surprised that I got to do that so young. I get in and start looking at the acceptance rates for people who were associate editors of the journal and how often they accepted the assignments that were sent their way. I'm blind to this. I have no idea.

I look across it. It's 10%, 15%, 20%, 15%, 10% and 15%. Nathan Price, 100%. I thought they were your assignments. I always I did that. I got into this pathological state where I was doing all this service work. I had to learn how to say no and be like, "This person will be upset with me. It's not the end of the world. It's fine." Those were the growing pains I had to go through. I was too agreeable early on.

The journal staff was like, "We're making him editor."

I was doing a ton of work and then one day I quit. It was a good experience. It was eye-opening to me, "I'm the guy that will do it." I also made lots of friends. I met lots of people in all these different ways. That's how it goes.

There's one other question then along these lines. What do you do to enhance your performance as a leader when nobody else is looking?

I'm always thinking about where I want the company to go or if it was my research group in the past. One of my performance reviews some years ago, which I got a kick out of, called me relentlessly future-oriented. I don't know if they meant that in a positive or a negative. It's the old Star Wars quote, "Never his mind on where he was." I do think about these things incessantly all the time because it's what I'm passionate about. It's what I like to think about. Even when nobody is looking, I'm probably trying to draw up some vision of what would be great to create or something. My mind doesn't rest very often from those things.

This show isn't that old but this is an emerging theme that comes out of the people I've been interviewing. It's curiosity but also thinking, being strategic and having a vision. It's not a scientific plan anyway because they don't have a broad sample size but it's a common theme for sure. You've got lots on your plate. How do you manage all your competing priorities? What do you do to prioritize things?

To the extent possible, this is one thing I loved in grad school. When I finished classes and I was starting to do research, the thing I remember commenting to lots of people at the time was that I loved it because I would get up in the morning, come in and think, "What is the most important thing I could do?" I would do that thing. I loved that in grad school because all I was doing was my research. I didn't have many people pulling on me. I could do that.

As you go further in your career, you start having more urgent things pulling on you all the time that you have to deal with but I still do try to think about that every morning, "What's the most important thing I could do," and then try to the extent I can do that during the day. I also have learned to ignore a lot more things. I'm a little harder to get ahold of. I'm a little harder to grab. I don't respond to every inbound email that comes in because you get lots of unsolicited emails that want to sell you. Some of them are interesting.

The other thing that I have become better at over time is time blocking to some degree. I try hard not to multitask anymore because I don't multitask in general. That doesn't mean I'm not 100% successful at that but I find so much more mental health and clarity if I think, "This is what I'm doing. For the moment, I don't care about any of the other stuff." I occasionally can't do that because you're in an urgent meeting and you're texting in the middle of something because you have to. It's impossible. I try to have time boxes where I do that.

One thing that helps me a lot is I have a fantastic executive assistant. One of the things that we have implemented is all my to-dos get put onto the calendar. If someone writes me and I say, "I'll do this," I see Alicia and there will be a time that will magically appear on my calendar for me to deal with that. That has been incredibly good for my mental health as well as for getting things done. I used to worry that because I get so absorbed in what I'm doing, I can be absent-minded about certain things.

I could accidentally forget to do something that I want to do for a person I care about. That's the biggest stressor for me. I don't want to fail in that way. To me, that has been a useful thing because I know it goes in. It's cataloged. It's on my calendar. If I don't do it, I will get hounded about it again. I do try to be thoughtful about it. I do think in the business world, it depends on what situation you're in. Prioritize what is important and then delegate other things or postpone them if they need to be.

I'll give you a chance to say anything else you want to say but the last question is this. What advice would you give a younger version of yourself?

I'm tempted to tell my younger self that they don't have to be quite as obsessive about certain things. The one big thing I want to say to my younger self is, "Never get out of shape." I do scientific wellness. My health has improved so massively but my health when I was younger during my 20s and early 30s was horrible. I never thought about it. I didn't think about it for one second. All I did, which is partly why I have a good scientific career, is I sat, read papers and wrote papers all the time. I wrote the most papers in the history of the department and sat there. I had carpal tunnel so badly from writing papers in grad school and so forth. Every hour, I would ice down so I could keep going because I had these big ganglion cysts.

What I would tell myself is personal care. I would try to teach myself all the aspects of scientific wellness. That has been my biggest regret because of the difficulty of trying to roll back the clock on things that I did that was bad health-wise when I became health-conscious and into scientific wellness and all the great things that have happened from that. I would rather have never gotten into that debilitating terrible health situation that I have to be climbing out of continuously instead. That's what I tell my younger siblings too. I'm like, "You're in awesome shape. Don't go through this bad period. Don't do that."

The title of this show is Beyond Publications. In a way, you got beyond publications because you wrote so many publications. You learned enough and built enough. It's a natural evolution that people have to keep in mind. You've got to write papers and do this but then at some point in your career, there's a switch where you say, "I've got the funding and the papers. What matters to make a difference?" What I'm trying to bring out in this show is that transition.

You get to that point where you write all the papers. You feel like you've got a bolus of information. It was one of the things that spun me a bit when Paul Jacobson called me up about this job and first, becoming CEO of Onegevity and then moving to the Chief Science Officer of Thorne. I was pretty much going to say no because I was very happy at ISB. I love working with Lee. We were turning in lots of great stuff. I still think that's a fabulous place. I loved it immensely. Paul's first line to me is, "Do you know what the problem is with all of you, academics?" I'm like, "What do you mean?"

He's like, "You want to have your figures at a million different pies. You can't look and see the one huge opportunity that is staring you in the face." I thought about it more. He said, "You've done all this work to generate all these things around scientific wellness, your academic studies and so forth but if you want this to make a big difference in the world, you need to tie these all up into one thing and make it work practically and financially, make it economically viable and something that works in the world." He gave me the opportunity to do that. I ended up deciding that was an opportunity not to pass up. I'm trying to do that. Hopefully, we will succeed very well.

It sounds like you're on the right path. I've learned a lot from what you said because I've been thinking a lot about prevention and interception but you've expanded my horizons in this way of thinking quite a bit. We have been going for quite some time. I want to give you the opportunity. Is there anything else you wanted to bring up, comment on or say?

We didn't get into it very much. I usually talk a lot about the microbiome, which is such a super interesting area for people. It's probably the area along with genetics that we have published the most on. The only thing I'll say there is the amount that we're learning about how the microbiome matters in health and aging are spectacular. Everything that comes into your body has to flow through the microbiome first, whether that's food, a supplement or a drug.

There was an interesting paper that came out showing that about 13% of drugs are metabolized away by the microbiome. The drug industry should care about that. We're going to try to reach out to them more about that. It could be the reason for failed clinical trials in many cases. It's interesting. We found that the microbiome becomes increasingly unique if you go through healthy aging. We did a study on 10,000 people that showed that the metabolic outputs of that microbiome converge so there were commonalities to it as people got older. We showed that if they stayed healthy but not if they didn't.

There's also this dense interplay between metabolites in the blood and how they inform the microbiome. That's going to be a rich area going forward. We're going to be doing some things in this space as well. That's going to be incredibly fascinating. I'm very proud of Thorne. We developed our microbiome wipe, which is a new way to get a stool sample, which is what it sounds like. It's special toilet paper that you wipe with. You throw it in a vial and you're done instead of the old approach that people don't like, which is having to scoop up a little bit of their stool sample.

With those kinds of things, the only thing I would close with is there's so much that people can do to get into their health. At Thorne, we're trying to make testing, insights and practical applications that people can do to improve their health better. This article I wrote for Scientific American highlights this whole emerging new scientific wellness industry. That's the other thing I want to end with.

There's so much of this that's happening. There are so many bright and incredible people that are on this train, building all the different pieces of it. It's an exciting space to watch as this all emerges. It's going to be an exciting future to see how this all ends up merging with healthcare and the pharma industry and ensuring the legacy pieces of our enormous healthcare industry. Hopefully, we can make this something better, more efficient and cheaper for everybody because we all know what's happening macroscopically with the healthcare system.

It's not sustainable. One other thing I can say is I think of the microbiome as well. It's another level of complexity than even the genome. We need to plow through that. Once we do, there's even more potential.

There's incredible potential in the space. There's no doubt about it.

Thank you a lot for coming on. I found it a very great conversation. I learned a lot. The audience will learn a lot. If people want to find out more about what you do, where should they go?

If they want to learn more, Thorne.com is where all the different products that we do and different programs appear there. If they're interested in finding out more about me, I'm probably most active on LinkedIn. I do a little bit on Twitter as well but LinkedIn is probably where I'm most active.

Do you want to say when your book comes out?

Thank you. If you want to learn a lot more, please buy The Age of Scientific Wellness and send me a note and what you think about it if you do. Everything that we talked about and a lot more is in there. That comes out on April 4th, 2023. It's available for pre-order everywhere books are sold online. It's coming out from Harvard Press.

You've given me a preview copy. I'll plug to say it's well worth the read. It's very well-referenced and researched. It covers what we said here and more.

I hope it's highly accessible. I hope it's easy to read. We have put a lot into making it accessible to anyone.

Thank you. Have a good day.

Thanks so much, Scott. I appreciate it.

 

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About Nathan Price

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Dr. Nathan Price is Chief Scientific Officer of Thorne HealthTech (NASDAQ: THRN) and author of The Age of Scientific Wellness. In 2019, he was named as one of 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. Previously, Dr Price was CEO of Onegevity, an AI health intelligence company that merged with Thorne prior to its IPO in 2021.

He has served for a decade 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. 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. He has co-authored more than 200 peer-reviewed scientific publications and given over 200 invited talks and keynotes.

 
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The Age Of Scientific Wellness: Bringing In More Precision And Scientific Rigor To Modern Medicine With Dr. Nathan Price, Thorne HealthTech