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#95: How to Upgrade Your Microbiome

Published on
June 14, 2022
Show notes

In Episode 95, Quinn & Brian ask: how can we upgrade our microbiome (also, what’s a microbiome (also, why does it need upgrading))?

Our guest is: Raja Dhir, Co-Founder of Seed Health a microbiome company pioneering the application of bacteria for both human and planetary health. He leverages years of expertise translating scientific research for product development to lead Seed’s R&D, academic collaborations, technology development, clinical trial design, supply chain, and intellectual property strategy.

So, what is a microbiome? Overly simply put, it’s the 38,000,000,000,000 little guys in and on your body that help you do stuff; the bacteria, fungi, protozoa, and viruses that work symbiotically and allow us to function. Interest in the field grew rapidly around 2015, but Raja thought the rate of innovation and commercial response was lacking, not to mention the science behind many of the products that were being created. So Seed leveraged the “foundry model” to support many startups in the field, driving innovations in everything from immunology to hygiene to cancer treatments while performing trials that were scientifically sound and blind as hell. They’re trying to learn all they can about the superorganism that is a human being and then make it better so that we can both live better lives and stop creating so many things that harm the planet.

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Transcript

Quinn: Welcome to Important, Not Important. My name is Quinn Emmett.

Brian: And I'm Brian Colbert Kennedy. This is the podcast, where we give you the tools that you need to fight for a better future for everyone. The context, straight from the smartest people on earth and the action steps that you can take to support them.

Quinn: That's right. Our guests, oh man, they are scientists, doctors, nurses, journalists, Brian, engineers, farmers, politicians, activists, educators, business leaders, astronauts, we even had a reverend.

Brian: Can I be a guest once?

Quinn: Once? Sure. Yeah, we'll do that, once. This is your friendly reminder, you can send questions, thoughts and feedback to us on Twitter @Importantnotimp or you can email us at funtalk@importantnotimportant.com.

Brian: You can also join tens of thousands of other smart people and subscribe to our free weekly newsletter at importantnotimportant.com.

Quinn: That's right, the weeks, all the science news you missed paired with specific action steps, again, that's our thing, you can take to kick some ass out there. Brian, on this week's episode we asked, are we finally able to upgrade our microbiome? Also, what's a microbiome? Also, why does it need upgrading?

Brian: I'll take an upgrade, yeah, sure.

Quinn: Yeah, yeah, you will.

Brian: And who better to chat with us about this than our guest today, he explains it all. He provides some tips and tools that you can take and his name is Raja Dhir.

Quinn: Raja Dhir, that's right. Raja is the co-founder of Seed Health and we had a real blast talking with this fellow. And I feel enlightened now. So pretty good, pretty good Friday.

Brian: Pretty good Friday.

Quinn: All right, guys, enjoy this conversation and we'll see you on the other side.

Quinn: Our guest today is Raja Dhir. And together, we're going to ask, how humans can finally start upgrading their microbiome? Raja, welcome.

Raja Dhir: Thanks for having me, guys.

Quinn: For sure, for sure, man.

Brian: Yeah, this is going to be awesome, I think. Very excited to have you. Raja, just get us going by telling everybody who you are and what you do.

Raja Dhir: Yeah, sure. So I'm the co-founder and Co-CEO of a microbial sciences company, called Seed Health. And my co-founder and I founded Seed Heath in 2015, at a time when the microbiome, which is the collection of organisms, microorganisms that live in and on the human body was really heating up as a field in science. I would probably say that there's been no field that's gotten as much enthusiasm or hype in recent years. It's kind of very similar to when the genetics and genomics revolution in the early 2000s came around. And we sequenced the first human genome and unlocked the role that our DNA plays in our overall health. The microbiome really kind of followed in that suit and at the time, there really were no serious companies that were championing microbes across a very wide range of applications.

Raja Dhir: So on the one hand you had some of these synthetic biology companies that were using microbes to tinker around, to make fragrances and try to synthesize new drugs, replace common additives in food and these big microbial ingredient companies. And then on the other side, you had of course, a very, very poorly regulated probiotics consumer industry. And then a few companies that were saying, "Well hey, maybe we can new drugs, but it's going to take us 10 years and so let's get started, raise a lot of money and hope we get lucky." Our idea at that time was based around this, what we call a foundry model, which was, look, no real breakthrough in a field that's moving as fast and as dynamic as the microbiome is going to happen within the four walls of any one company or even any one academic lab for that matter.

Raja Dhir: And so we put together this foundry model, where we built companies with leading scientists as co-founders within those companies, focused on their particular area of domain expertise. And so we have one in women's health on the vaginal microbiome, we have one in consumer health on gastrointestinal benefits for consumer probiotics. We have one that we haven't fully announced yet, but it's working on making cancer drugs better. So it's really like this broad tapestry now that spans gastroenterology, immunology, neurology, and then of course, these really radical new applications for personal hygiene. Things like how you brush your teeth, what you put on your skin, what you feed your infant. All of these areas are really going to be disrupted by microbial sciences in the next, I would say 20 years. And so that's kind of our area of work and thesis of the company.

Quinn: I love it, man. That's awesome. Well, that's really where we're focused. I mean, I think we all love sci-fi, but we're trying to harp in on here, is the things that are affecting everyone now or in the next 10 years or so. And like you said, we sequenced the genome and that's become more broadly available, and cheaper, and faster. What that means is it's applicable to biotech and things like that. And then like you said, digging into the microbiome here and how much we've discovered. And yet, how much we've also discovered on the scope of how far we have to go and how much we don't know, is going to be really, really fascinating here. So I'm excited to dig into that today.

Brian: Yeah, yeah, yeah. Let's do that. Raja, we're going to provide some quick context for our topic, our question today. And then we're going to get into some action oriented questions and actions that everybody out there can do to help support. Sound good?

Raja Dhir: Let's do it.

Quinn: Awesome. Raja, we do like to start with one important question. Doesn't have to be too terribly long, but should be honest. Something to set the tone a little bit, it's fun. Raja, instead of saying, tell us your entire life story. We like to ask, why are you vital to survival of the species?

Raja Dhir: I'm going to answer it a little with a contrarian answer, which is, I actually do not think that I am vital to the survival species. Nor do I think that any human is, nor do I think that humans as a species should be privileged over any other species.

Quinn: I love it.

Raja Dhir: So in fact, I think that, that speciesism, I don't know if that's a real word.

Quinn: Let's go with it.

Raja Dhir: Is a right limiting step in our advancement as a civilization. And part of what we, as a microbial sciences company really anchor into, is this idea of ecology and ecological systems and networks. It's the basis of most of the technologies that we work in or develop. And when you look in an ecology, you really see, I mean, I am not the first to propose these ideas. It was actually Alexander von Humboldt, back in the early to mid 1800s, who was a big inspiration for Darwin, that pioneered this idea of ecosystems being interconnected and highly dependent on one another.

Raja Dhir: It's of course, something that we take for granted now because we can see the ripple effects when you pull at one thread, what happens elsewhere, combined with our pretty, I would say, hands on role in shaping the environment around us. But really, I mean, my point is that I think that to advance the survival of our species, we have to deconstruct our role at the top of it. It's a strange answer, but I would answer it with a bit of humility I guess.

Quinn: No, I think that's fantastic. I mean, that's totally true and that's why we work hard to have people on the... Look, this could easily be one of the shows that has a bunch of famous corporate white guys on it. And I endeavor not to do that. We try to find folks who are out on the frontline, doing the things. And thankfully for everyone, and for our benefit here. It's a very diverse crowd and often, not the biggest names. And so we use that question as a way for people to be bold, to talk about why they feel like what they're doing today.

Quinn: But I love and fully agree with the contrarian take, that the longer we exclusively prioritize ourselves as a species, the deeper the hole we're going to dig here, clearly. And that goes as far as all these external ecosystems that we've spent at least the past 100 years completely demolishing. But also, the type of ecosystems we're going to talk about today, the very, very tiny ones. So let's just do some really simple context around that because as our listeners know, a lot of them, well they're usually probably texting and driving or something of that sort. Probably not doing as much of that these days, because they're locked at home.

Quinn: But probably dealing with their children or something. So sort of lowest common denominator stuff. So what is bacteria, right? They're very small, microscopic, single celled organisms. They are basically as old as time. They're incredibly adaptable and they live everywhere. As far as we know now, they make up half of your body space, inside and out. They turn milk into yogurt, they digest our food, they fill the oceans. They are the things that live in healthy soil, helping to grow our food and suck down carbon.

Quinn: And historically, they are something we've been progressively from negligent to massively misunderstood, to something we're really excited about. There has been a recent push to explore how to understand them, how to improve our own microbiome. Mostly focused on the gut, and it's been a very interesting, curvy road to say the least. So I am really excited to dig into this and to ask, can humans, can each of us finally start to 'upgrade' our microbiome, with actual science, not just snake oil? And-

Brian: Oh, snake oil.

Quinn: And what that really means. No Brian, snake oil is not a good thing, remember.

Brian: Oh, it's bad, right?

Quinn: Yup, yup, yup. So Raja, I feel like I can safely venture to say that for the majority of us, even our nerdy listeners, who are nerds and scientists and engineers and all that and regular people, our best understanding, our most base understanding of the microbiome is in taking antibiotics once a year or so for some sort of infection. Hopefully something relatively harmless, but they do seem to be, and troublingly have been the default answer to a default case, right? Rogue bacteria, making it sick and that goes all the way back to van Leeuwenhoek, and Pasteur, and Lister.

Quinn: But that's not the full story obviously, of what we're talking about. And there's been a lot of really interesting, conflicting ideas in science. And you hinted in our offline conversation a week ago or so, about how your experience as a debater has let you have this ability to form and hold these competing ideas in your head, and to be able to justify both. And I'm curious how that enables you now, in 2020 and in operating this holding company idea of new concepts and new trials. To try and understand and operate in this very complex world of microbiomes. I'm wondering if you could speak to that a little bit and why it might be an advantage.

Raja Dhir: Well, it's kind of a paradox, right? So debate and my extensive background in it, I've joked before, kind of can make you a bit pathological because you can argue the same thing from both side equally persuasively and that makes you crazy person. Because most people are brought up forming their opinions of the world, engaging with the external environment, building their thesis and how they want to engage, developing these things called morals. And just trying their best to stick to it and in some ways I really envy that kind of simplicity, not because I think that it's ignorantly bliss or anything like that.

Raja Dhir: But just the mental gymnastics once you've, I should say unlocked your ability to deploy reason in such a targeted way, the mental gymnastics that you're playing with yourself each and every day are quite frankly, it's both exhilarating and exhausting. And make it even more challenging to try to build a science company because the scientific method at its core is essentially observation without attachment to outcome. Whereas debate is quite literally the opposite, which is build your hypothesis and thesis first and then manipulate information to advocate for that point. So really there's been, actually I would say not much of an advantage, but actually a lot more of a rounding out I should say.

Raja Dhir: And typically, the types of people that excel in debate, go on to do politics or law. I do know some people that were also equally competitive in kind of the top three or top five with me when I was competing, that did go on to medicine and did great. But that's really the anomaly, right? So mostly advocacy becomes a lens through which you see the world. And it really helps in social issues for example, so like the ability to surface issues that might be overlooked by society at whole and put some gravitas or weight into them, is a great skill from debate. But really, when it's come to the microbiome, when it's come to building this type of a company, debate has served me probably most importantly. And I would say, one way comes to mind, which is to build a company with the best, you have to convince the best that the idea is worth building.

Raja Dhir: And oftentimes you have aggressive competition. And so for all of the scientists that we work with, that we built our companies with, I mean, they really are the best in their field. And so, probably dozens, including a handful of the venture funds, or what's called now these venture factories or creation incubators, whatever you want to call them. The model for biotech is now really going so far upstream, where the top funds, like the flagships and the archers, they want to find a radical piece of science, ask a couple of crazy questions and then build the company from the ground up because that's where you can realize most of the value.

Raja Dhir: And so it's highly competitive, particularly when you're relatively young, in your 30s. You don't necessarily have five or 10 companies that have gone public under your belt yet and it really comes down to how well you can sell an idea of the future without blowing air. Because one thing that scientists are really sensitive to is, kind of like verbiage or vacuous and devoid of substance thoughts. So I would say that probably that's the aspect where debate has really helped in kind of 'selling the dream'. But then of course, that's just your foot in the door. If you don't get good clinical data, or you don't go raise the right amount of capital or hit your early development milestones, then you've introduced a lot of issues into your future plans.

Quinn: Sure, sure and that's what's great about if you... I mean, it seems insane to some people and clearly not what we're dealing with at the moment. But that's what's great about building the fundamentals of a company and its outcomes around science and a scientific method, which is like you said, you can use debate to sell it one way or the other, over and over again. But it comes down-

Raja Dhir: Yeah and I give that advice to entrepreneurs all the time, which is, I'm very hesitant when people are overly protective about their ideas because the value that you get from pressure testing your idea gets the best in the field, so far outweighs the risk of 'theft'. So much of it is execution dependent and people dependent. And everyone should jump at the opportunity, if the people that are experts in the area that you want to make an impact in, aren't really fully sold into the idea, that's totally fine. But then go and do the work, so that when you come back to them next time, they are.

Quinn: Yeah, I love it. I love it. And that applies to everything. I mean, my day job is screen writing in Los Angeles and everyone's, usually newer writers will get very excitable about, "Oh, I had this idea and then I heard someone else talking about it. And it was a friend of a friend and did they steal it? And this and this." It's like, you got to execute it. You got to go out there and execute it and the best thing to do is talk to 10 people about it.

Quinn: You can't be worried about them stealing it, because if nine out of 10 were just like... it's not worth it, or that's been done, or whatever it is. There's no point in spending all this time on worrying about who's stealing it. And by the way, if someone's stealing it, it's probably a good idea. So get out there and do something about it. And like you said, start pressure testing. And pressure test yourself first, which is like, are you the one capable of executing this thing? What are the assets you need? What are the people you need on your team? And I think that can make a big difference.

Brian: I actually had the idea for Terminator before whoever did Terminator did.

Quinn: You weren't even born, Brian. Yup. Raja, again, coming back to, and I feel like these podcasts get nerdier and nerdier the deeper I dive into this stuff. But I do really enjoy it. Want to talk a little bit about first principles and systems thinking. And it's rapidly becoming just sort of fundamental building blocks of how I consider everything, from how I raise my children in COVID, to how I conduct these things. But it's something I'm always endeavoring to understand better and it matters so much today, right?

Quinn: If you're, again, trying to think as objectively as you can about systems thinking. And that can be climate inputs, global trade, the markets, COVID, but especially bacteria, right? From my again, very limited understanding, we, science, has come to understand that the bacteria that are in, and around, and on our bodies seemingly are, I don't want to sell this too far, but kind of in control of the whole shebang. Is that incorrect?

Raja Dhir: Yeah, so in control, the direction of the control is a little, we can expand upon that. But what we can-

Quinn: Yeah, please.

Raja Dhir: What we do know is that bacteria are intimately involved in virtually every major organ system in the body and-

Quinn: From the second we come through the birth canal, right? I mean there's even been studies on that, about what the mother passes to the baby. That's your first dose.

Raja Dhir: Yeah, that's actually called, that process of the first microbial vertical transmission from mother to child, is called seeding, which was the inspiration of our name as a company. So absolutely, I mean, and I would argue, even more important in those early development windows, than what you would see after kind of either the microbiome or the host has reached what's called steady state. So kind of matured or the immune system is developed. A lot of these experiments, they look at what happens during that period of time?

Raja Dhir: And some of the experiments, I've even gone so far as to show that a single course of antibiotics or even more interesting to me, is a low fiber diet after three generations of animal, child, animal, child, animal, child in a mammal study, in a mouse model. You show that you have a mass extinction and a die off of organisms that were originally present in the great grandmother in that experiment. So to me, that's really, that work was done by Justin Sonnenburg out of Stanford. And he does really elegant diet at the intersection of microbiome type of studies. But it's not just what you would think is right on the nose, like antibiotics. Even lifestyle and diet can affect your gut microbiome and affect the microbiota of your offspring.

Quinn: Yeah and that's what I would love to dig into a little bit because again, the more we're finding out the things that we put into our bodies and where we live, and the air we breathe, and the water we drink, and the drugs we take, they're affecting these clearly highly complex systems that we're only beginning to understand. So I'd love if you could talk a little bit about, as you're developing new ways of improving of modifying on, or protecting this ecosystem, that each of us have inside of us.

Quinn: And they're all vastly different. And like Ed Yong said, the bacteria on your left hand is so different from the bacteria on your right hand, it's fascinating to me. So I'd love to hear you talk a little bit about how you consider that system and all the levers and the inputs as you're, again, sort of developing these new ways of considering it and what you can do to evolve it.

Raja Dhir: So I'll draw a parallel between the human microbiome and actually classic ecology, which is that if you think about species loss, or habitat loss, or deforestation, whichever, or pollution or carbon emission. I mean, whichever aspect of environmental science you want to look at, I would say that today, and certainly when environmental science first really came online our approach was kind of a little bit along the lines of what you'd call the precautionary principle, which is we don't know the extent of our impact. And so we should err on the side of caution, of conservation. We shouldn't let species go out, we shouldn't allow for terminal lineages of specific species.

Raja Dhir: We shouldn't impact the biodiversity of isolated ecosystems until we know the role that which animals and participants in any single ecosystem play a critical role. And then kind of like, if you think of it as a spectrum, that approach from conservation can go as far as more active approaches, like ecosystem engineering, or de-extinction. Both areas that I work on academically and with collaborators. So with the human microbiome right now, we really very much are in this kind of, the field started by looking at what's called the ancestral microbiome. You're looking at hunter-gatherers, you're looking at groups that have never been in contact with Western lifestyle, with modern living, with modern drugs, with hospital births, like the whole process of modernization.

Raja Dhir: And I can see the attraction to it, and it's even gone so far in some of Ed Yong's books and even others, to say things like, "Well, let them eat dirt and let them go out into the wild," and this glorification of the ancestral microbiome. In general, I agree that, that's a good thing. Diversity of your gut microbiome across every single marker is associated with markers of health, regardless of the outcome that you're looking at. Except one could argue, very, very late in life, in very specific conditions, like Parkinson's, we might see that be a sign that there's some dysfunction because all organisms are now permitted to live. But for the most part we can say diversity equals healthy microbiome.

Raja Dhir: It's resilient, it has functional redundancy, it's not overrun by any opportunistic organisms. So that's kind of our approach and again, I think it's a bit of an oversimplification. So if I've looked at the microbiome of the Hadza tribesmen and of the Venezuelan Amerindians and you couldn't pay me to take half of the organisms that are in there because quite frankly, I didn't coevolve with them. They weren't with me from the early stages, and we actually don't know, just because they're there and they predated us that, therefore they're good.

Raja Dhir: And so the waves kind of going back and forth, which is the first is saying, everything should exist and look how far we've been removed from our ancestral microbial communities. And then the other side saying, "Well, we don't need a lot of those organisms to live in a modern world." And in fact, some of them actually could be dangerous later in life or could be opportunistic. And so I don't want to say it's as simple as more organisms are good. But certainly this idea of looking at the organisms together, whether you look at it from an ancestral microbiome or whether you look at it from a modern microbiome. The idea that they all work together as an ecosystem certainly rings true.

Quinn: Yeah, no. I love that thinking about it and I do think it's important to step back. And like you said, yes, taking on principles that we have clearly in the Western diet and Western environments done so much to destroy the diversity in the ecosystem, that we have evolved with. But that doesn't mean we shouldn't take some time to really study in those folks that still have a much more diverse microbiome, what's going on in there because like you said, you don't want to just drop that into the melting pot without having any idea what's really going on.

Raja Dhir: And I can give you a couple of examples. So again the kind of popsci version of it is like, oh, ancestral microbiome or it taps into these undercurrents, which is why the paleo diet is so intuitively attractive for people because it just feels, because it's more how we evolved, it feels like it should be more right. It just taps into this deep, deep drive, or desire, distrust of modernity. But that's not the way that this field really, in its highest form really thrives.

Raja Dhir: And so for example, in our women's health company, in 2004 the founder and chief scientist, Jacques Ravel, started to characterize the microorganisms that live in various ecosystems, gynecologically, obstetrically, and then a little bit in terms of what's transmitted from mother to a child. And for 10 years, gathered data on hundreds and hundreds of women and followed them over time, to first establish that baseline of, let's say what's there, let's map the genes, let's build a gene catalog and library. And then after that, then you say, well what are some features from all this big data that are important and valuable?

Raja Dhir: And you really need so much data that you can start to say, well, these genes or these alleles are associated with stability or these alleles are associated with not having outcomes like UTI, or BV, or a preterm birth, or infertility and the list goes on and on. And then from there, you start to probe and build a hypothesis. And say, well these organisms or these network of bacteria together, based on their genomics, based on their transcriptomics, based on the functions that they serve look like they should be really important. And then you try to reconstitute or grow culture back out and grow and build this ecology of organisms that you then transplant back in.

Raja Dhir: And so every time you see people marketing like a single organism or a single probiotic, it's really challenging for me to believe that those end points are valid because we know how much of these things they work together or they work with overlapping and redundant mechanisms that are really important. So another example is, starting to look at bacteria in the gut, in our other company, that's being built with Caltech, for literally 20 years, they just been studying one bacteria. And in the last three to five years, have uncovered the part or the components of these organisms that make it interact and 'talk with the immune system', right?

Quinn: Mm-hmm (affirmative), mm-hmm (affirmative).

Raja Dhir: So when you're thinking, you really have to think a lot deeper about this stuff, other than, "Oh, if I just take this then it'll be good for my immune system." These things are highly complex, network driven responses in the body. And so the main takeaway that I have there, is your research should be driven and designed to answer the research questions that you ask. So I'll give you another example. So we built a consumer probiotic, which is 24 different strains of bacteria that are all coexisting together in a single capsule. And some of the research questions that we asked early on were, well, are there organisms that we can ingest, which prophylactically or preventatively engage in really validated ways across a ton of different mechanisms, with the body that improve health?

Raja Dhir: And so the question is, well, what are those mechanisms? There's your digestive functions, you should have things like normalization of bowel movements, intestinal transit times, stool consistency, bloating. I mean, the number of side effects or of quality of life index markers that are associated with your digestive system, are quite vast, right? And so 300 person trial on that, for two of our dominant strains and then it goes on. We have bacteria that make micronutrients, that synthesize vitamins, you have bacteria which signal through the gut skin access. We have bacteria which are involved in cholesterol reuptake for your cardiovascular panel and to maintain your lipids.

Raja Dhir: And this is really deep mechanistic science, right? This works through creating an enzyme called bile salt hydrolase as an example. And now we're actually probing this cocktail in some even more novel research questions. For example, what happens after you take antibiotics? And we got the initial data back and we found that our cocktail actually results in the production of a very, very valuable metabolite called butyrate, way faster than, not only just spontaneous recovery, but way more than the original host before they even took the antibiotics and so it's this kind of like-

Quinn: Interesting.

Raja Dhir: ... rescue effect. And another area that we probed this research question was around other things, which can be destructive to your microbiome. And so naturally when looking at what all those things can be. They can be poor sleep, they can be nonsteroidal antiinflammatory drugs that can actually be very, very aggressive high intensity interval training exercise, they can be alcohol. And so we naturally zeroed in on everybody's favorite drug and designed the experiment to say, well, does alcohol consumption have an effect on your microbiota, and your host cells, and your intestinal cells? And can we rescue or attenuate some of those side effects? And we saw the exact same thing.

Raja Dhir: We saw that it rescues intestinal cells, we saw that it results in a faster recovery of the microbial communities. We saw that it again, starts to catalyze the production of some of these metabolites that are really important. So important that actually, your human cells use these bacterial metabolites as a primary energy source. More than energy that you ingest from food. So a very intimate cross talk between these cells and your bacteria. And so I'll pause there. But these are the types of research experiments that I think are really, really interesting to validate some of these applications for bacteria.

Quinn: No, I think it's great and thank you for speaking so broadly on that. But that is the point that I feel like I endeavor in every conversation I have, whether we publish it or it's a private one or a minor, whatever. Might be with loved ones, which is to, you referenced mechanics, which is essentially without the literal definition, how things work. And they do not work or at least, they do not do the full scope of their work in isolation. And again, that comes back to the market or climate levers or bacteria. I mean, this is the problem with so many of these dietary studies, that you'll see on cnn.com or something, sorry CNN.

Quinn: I used this example in another conversation this week, which was, one day it'll be vitamin E will extend your life two years. And then the next day, another peer reviewed study, vitamin E will give you a heart condition. And it's just like yes, but that is such a simple, ignorant way of looking at this. And when you don't consider everything, when you don't consider all of the levers because this is such a comprehensive connected world. And so is the world of bacteria. You are doing more damage than if you'd otherwise just left it alone. So yeah, those things are so important.

Raja Dhir: Yeah, 100%. But it's a bit of a chicken and an egg because there really is no good way to design a diet study, unless you can capture everybody and put them all in a ward together and control everything. For some, again, one takeaway I want people to have here is, the study must be designed to answer the research question that you ask. And so for something with a short time horizon, like does a high fat diet increase your blood cholesterol levels? Yeah, and that's exactly how this association between dietary fat and even also, dietary carbohydrates. Both have been shown to impact your cardiovascular health through the production of low density lack of proteins and very low density lipoproteins. But you can do that because after a month or two months of altering someone's behavior, you can start to see a change.

Raja Dhir: But the diet studies that kill me are the ones that come out and say, this and this decreases or increases your risk of, or like vitamins do nothing and then you look at the study and it was a study that didn't control for anything on people that started taking Centrum vitamin like 20 years ago, or 30 years ago. And looked at how many people that took the vitamin had more all cause mortality than people that didn't. And it's just, there's so many other things at play there, that I would consider that data such low quality, that you should just let it go. I mean, if you can find a good mechanism, then you can impute that vitamin E or vitamin D or whatever it might be, is involved in a certain biological process. And we just have to leave it there and both sides are guilty.

Raja Dhir: The micronutrient or the dietary nay sayers, they say, "Oh, vitamins have been shown to do absolutely nothing," based off of this horrible study design. And then the evangelists, they'll look at a small controlled study or cherry pick a little bit of data and be like, "Of course, you should take vitamin D3. It's involved in, as a prohormone for this, this, this, and this." And everyone needs to, I think the whole diet has become politicized and weaponized. And it really shouldn't be that way. I mean, there's a couple of simple things that we can find a lot of common ground on, that are really actionable.

Raja Dhir: For example, the microbiome is a great lens to look at diet and we can say that based off of the Human Microbiome Project, part 2, the people that had the most diverse and resilient microbiota consumed over 30 different types of fruits and vegetables in any given week. Whereas the people that had the least diverse gut microbiota consumed less than 10. And so very, very simple stuff, which is like well, maybe for people that are creatures of habit, don't eat every day for breakfast, maybe try to switch it up a little bit because you get different phytonutrients. And so, again, I don't think that's going to blow anybody's mind, but these small kind of-

Quinn: No, it isn't. But yeah, they're fundamental building blocks that are relatively simple to understand and to study, which is just like, it's like the Michael Pollan thing, right? Which was when everyone's like, "Oh, you've written all these books and all this stuff," and what's his great advice, it's like eat... What is it? It's like eat food, mostly plants, not too much. And it's like, yeah, if we have to boil this fucking thing down, fine, let's do it that way. Of course, it's just like eat real food and more variety and there's the study. Now we can do more specific stuff. Brian, I know you wanted to talk about some of the Real World products a little bit more.

Brian: Yeah, yeah and Raja, you were talking about it. So yeah, let's just talk about that a little bit more. Probiotics and prebiotics have made quite a name for themselves over the past decade or so. And it's not always in a positive sense. I mean, from bottles that are just labeled probiotics, to no one in the general public really having any idea what's in them, much less what strains we should all be looking for and why.

Brian: To suspect ingredients from China, to suspect results. And there's just still so much we don't know about our microbiomes despite how much we've learned so far. And we've begun pulling the thread of this sweater, and it just seems that there's just so much more and more to unravel, which is super exciting. But also calls into question the appropriateness of health marketing products without firm ground to stand on.

Quinn: Yeah, I mean, I think Ed had a great quote in his book, which is also similar to one that my fertility doctor had at one point. I think Ed said, "There's no such thing as alternative medicine, if it works it's just called medicine." And I remember when my wife and I were having trouble making kids and at some point, when you're very desperate, you start to believe old wives tales and alternative things, whatever it takes. And I remember us asking the doctor once, "Oh, they say if you're carrying the child high in your belly, it's a boy. If it's low, it's a girl."

Quinn: And he's like, "If that was true, it would be called medicine and it's not." But that's kind of what we're always trying to deal with, is to get as reputable as we can. And I think Brian's right, which is just like, probiotics have made themself some very complicated press over the last 10 years or so. So I think we're just curious like, why is now the time to take a new product to market? And I guess, what makes for example, Seed's efforts and products different? Where's your product moat when it comes to this?

Raja Dhir: Yeah, well I mean, I fully agree that science can be a great equalizer and it should be a validating tool. If it's medicine, it should be just a medicine. It's why we have areas that we bring to consumer products to market, as well as have to take things through FDA trials to get drug approval. So we're really familiar with this idea that the research burden must be met to validate the experimental or research questions or projects that you might be working on. And even on a larger note, humans, so much of the stuff just goes back to human behavior. It's the desire to believe. I was reading an article on why conspiracy theories spread so fast. And it's because if you think about what a conspiracy theory, well first of all, it's oftentimes more exciting than the truth, which is a lot more data driven, boring and takes a lot longer. So there's that-

Brian: Or is it the truth?

Raja Dhir: Yeah, that exactly segues into the second, which is the thought leadership that can be earned they're provocation by flipping a question, asking it with suggestion that the answer is something different, or using one blind spot in the information to raise doubts about everything else that may not even have those blind spots. I mean, there's so many ways which just the framework of question asking can lend itself to the promotion of conspiracies. And lastly, from a psychology perspective, this is the one I was most interested in, which was if you think about the human drive of course, to feel heard, to feel intelligent, the need to serve our ego, whichever way that might present itself.

Raja Dhir: A conspiracy makes the conspiracy theorist feel as if they have access to some privileged information that only they have stumbled across, that the rest of the world I missing, without actually having to go do the work to learn or develop or sculpt that position, that it might be in. So a conspiracy theory can be as outlandish as the belief that you they've stumbled across the source of extraterrestrial life or it can as 'benign' and innocuous as the fact that coconut oil can cure your cancer and everything in between. And so I really think that it's really multifactorial what explains the propagation of 'alternative facts' and conspiracies is actually more driven by human behavior than it is by 'natural products marketing'.

Raja Dhir: I don't the coconut oil industry wakes up every day and they're like, "Absolutely, we're going to corner the cancer market." It's just kind of a weird phenomenon that's also based on the fact that the overall level of scientific education for most people in our country is quite low. And so with that, I'll answer your question about probiotics, which is, I actually really hesitate to use the term, in using the term, you kind of lend credence to everything on the market that has positioned or marketed itself as 'probiotic'. There's really kind of birth of the industry was in the '80s and '90s, some people that worked in fermentation and in fermented foods. So yogurts, and cheeses, and fermented teas, and so forth. They started to find really scalable processes for growing and at very high yield these bacteria.

Raja Dhir: And they thought, "Well, we can just deliver them directly, these lactic acid producing bacteria, rather than in food format at much higher dosages." And that's kind of where, from the unscientific side of, I would say probiotics began actually well before we even knew about the microbiome in the way that we know today. So there's kind of that baggage I should say, of an industry which was birthed as a result of the food industry, well before microbial sciences. And then you would say kind of the other side of it, is the human microbiome research, which says, "Well, what if we can isolate human drived bacteria that have very unique functions and then see if they can be given back to humans to improve health in [crosstalk 00:45:47], right?

Raja Dhir: That's what answers the question about timing, is that a lot of our research was very clinical and mechanistically driven, which actually has very little to do with how good an organism is at fermenting something. And actually more the pedigree of the organism, where and how it was isolated, what the mechanism of action is. Whether there's been, when you give it back to humans and screen it against a placebo, whether you can get a signal compared to a direct placebo in a direct interventional trial. These are kind of more of I should say the research questions that we really try to answer.

Raja Dhir: And so, our research moat is that we went back to the birth of scientific side of the term. Our chief scientist chaired the United Nations and World Health Organization panel, that authored the definition of probiotics in 2001. Which actually has a very heavy emphasis on validating that an organism has a benefit in humans or in their host before it an qualify as a probiotic. And actually, him and I published a paper last year in Frontiers in Microbiology, which outlined the strict requirements that something much, a strain must meet before it can technically be considered a probiotic. So I bring all that up to say, which is it's not throw the baby out with the bathwater. In this case, it's put the baby in with everybody else's bathwater.

Raja Dhir: And I don't think that just to get definition straight, it's a very important distinction to have upfront. But then in terms of what's the scientist moat? I mean, look, we have done or are doing randomized, controlled interventional human clinical trials on our product in a wide range of applications, blinding ourselves, blinding the researchers and most importantly, blinding the bioinformaticians, the people that are looking and analyzing the data afterwards, to what was the intervention and what was the control. And we're doing that at institutions like Harvard, for IBS. We're doing that in Canada at the moment, for antibiotics. We're designing a huge series of research questions and experiments that start to answer very specific questions about why this cocktail of bacteria could be good for you.

Raja Dhir: And we really just don't see other companies that have or are putting as much of an emphasis on this type of traditional life sciences approach and then publishing that type of data to peer review. And so from our approach, at least I would say that's what makes us, from the people that are involved, to how we think about validating and doing the science. I would say it's a completely different approach, but I can't in good conscience, back up or support kind of 'the larger probiotics industry' at large because I think that it is unregulated, there's a lot of fast and loose research. Anecdotally, people say that some things really seem to help them. If they do, I would say that it's kind of a glorious accident, where-

Quinn: Sure, or the placebo effect, which is real. But it's just crazy when you hear people go to legitimate, very good doctors, who maybe they're having some IBS or whatever it might be, or their ecosystem has just been demolished by taking antibiotics a couple of times in six months for a sinus infection or whatever. And have them say like, "Okay, well try to eat a wider variety of fermented foods and take a probiotic." And you're like, "But that does nothing for anybody."

Raja Dhir: Yeah, well and also-

Quinn: So is that, I guess, the value behind your cocktail of all the different strains? If you just want to take a minute and talk about just the product itself. Like what the consumers are buying.

Raja Dhir: Yeah, so have 24 strains that we've assembled together and actually, it would not really possible to deliver this in any other way, other than what's called lyophilisation. So you take the strains, you culture up each bacteria individually and then you sublimate it. So the water leaves it and puts it in this kind of state of suspended animation. And then when it comes back in contact with water, they become re-hydrated and become metabolically active. So in food, for people who have this perception that like, "Well, I don't want to take a pill. I'll just get bacteria from food."

Raja Dhir: But bacteria in a fermented food are in this is state of metabolic activity and so they're kind of like competing for nutrients with one another. They can only persist for so long before the energy source runs out. So really, if you want to assemble what's called a consortia or a complex consortia. Really, you have to put them all together and assemble them in this way, which is what we've done. And I'm hesitant to say that this is going to work on IBS because to go back to your example and until that data, we're in the middle of a trial right now, that's assessing this against a placebo. And then we can answer that question with research, very directly. But IBS is a really poorly defined condition. Actually, placebo works 30 to 40% of the time in IBS trials and that's actually better than most drugs, right?

Quinn: Right. The placebo science is like an entire other conversation I want to have. It's just, it's mind blowing.

Raja Dhir: Yeah and there's nothing worse than an IBS, so actually, we had to design what's called a placebo run-in. So for a week we give everybody something and don't tell them and look at their data. And we give everybody a placebo for a week and the ones that report like they're getting dramatically better, we don't include them in the trial, so it's called a placebo run-in. It's a very scientific method to isolate out those kind of people that are the absolute worse to include in a trial because they just make your statistics so impossible to read, right? Because they're saying that there's this huge benefit without actually having it, so you don't get a clean read.

Raja Dhir: But anyways, again, with this first product, we kind of wanted to say, "Well look, there has to be better science here." And so, one of the first technologies that we employed in screening and validating different organisms was the technology that came from the genetic school at Harvard and it was again, this is kind of a very, very technical, but at a high level, it looks at a transcription factor in the gut, called NRF2, which is involved in the gut's response to effective detoxification. Not in a natural or pseudoscience way. But the actual act of processing, handling, and removing toxicants from the body.

Raja Dhir: And so this is a really good transcription pathway as a hallmark of like which organisms engage the host, right? Which organisms engage pathways in the host, instead of just going there, produce a little bit of lactic acid and then just pass right out? We used this, we screened it, we got a great hit, we built our consortia and cocktail using this technology and then the strains that we screened in that process that we used to build our strain bank, our strain library, carried this large pedigree of human clinical data. And primarily from Northern Italy.

Raja Dhir: That's where all of our fermentation happens and that's because in Northern Italy, biofermentation and isolation of microbes or probiotics never kind of became like a consumer industry or as a food industry the way that it is in The States. It always was just this very close discipline between fermentation facilities and hospitals and clinics. And so a lot of the hospitals and doctors offices, a lot of these clinical trials were run in collaboration, right out of the gate. But again, I think one of the things that makes it interesting, is the fact that there is this level of publication on these strains, right?

Raja Dhir: So a cocktail of strains that signal to the gut, skin access that's in our consortia, was published in JAMA Dermatology. JAMA's one of the top medical journals, world. A lot of these experiments were designed, validated, hit up against a placebo and then analyzed and published afterwards. And look, that's not to say that everybody's going to be a perfect responder. I mean, we even know that in some of best 'drug cases' you have responders and you have non-responders. But what that does, is it starts to tease out the real signal is based on a product versus what's more likely to just be chance or a response to placebo.

Quinn: Sure, well again, certainly appreciate the broad scope of your investigation into the microbiome and these bacteria and how they interact, which is just again, so key. I think a big key from this conversation, and is one of my life's missions, is just ask better questions. Whether it's someone conducting the science experiments, or as a journalist, or as a politician. If you don't understand it, and this is what we try to do so hard here is, establish context, so people can take action because action is great. But action without context is kind of what can get us in trouble or just is an innocent wasted effort, or money, or bandwidth, or whatever it might be.

Quinn: But asking better questions, pointed action oriented questions I think, will enable these things to go further. And in doing so, and considering the broader systems and the broader levers, will take us further. When I mentioned this to a bunch of people, I want to make sure we don't miss antibiotics here. So if we could just spend, before we get to the action steps, just a brief clarifier, like antibiotics are not the bad guy here, right? It's just that we've used huge numbers and combinations of these to for sure, markedly improve human life and lifespan. This is one of the bullshit things about the paleo diet, is everyone's like, "Oh, it's the way we used to be."

Quinn: It's like, yeah, but life expectancy was like 33. So there's a huge reason why, for example, World War II was so different from World War I, right? But they are in effect, many of them, carpet bombs, right? They've gotten the job done and they get rid of whatever might have been making us sick. But they do a huge amount of collateral damage and the problem is, the bacteria in our bodies are so ancient and smart and they adapt so quickly and efficiently to these weapons, that we're effectively running out, in a lot of ways. Even for innocent things like strep throat, effective antibiotics. There's entire diseases that don't respond to them any more.

Quinn: I'm just curious if, and I know this isn't exactly where we were going, but just for a moment, if you could talk about, and again, none of us are medical doctors here. But do you foresee any future where we figure out how to use fewer of these things? Having had some private conversations with some of the people that are working, scientists are working very hard on these things, are looking for new antibiotics in caves or in the bottom of the ocean. They're very worried and I'm just curious from your perspective, having worked on it. Again, if you could just take a moment and think about this with me.

Raja Dhir: I'm really, really nervous about antibiotics losing their efficacy. And it's a love/hate relationship. I think that they're one of the greatest advancements in medicine. It's absolutely a tool which would never have been possible for an entire range of conditions that would have killed you in a very short period of time, prior to their discovery. So their mechanism actually is quite varied and when people talk about antibiotic resistance, you really have to know there's, like you said, an evolutionary arms race between bacteria. So actually most antibiotics are derived from compounds that are produced by other microorganisms as part of their arms war against one another. And it's the same way that like CRISPR was discovered as a tool by bacteria, to chop up viruses, right?

Quinn: Sure.

Raja Dhir: So if you look in, at that very fine scale level, you find that there's a ton of tools for organisms. The reason that we don't have a lot of new antibiotics, is because antibiotics are, and this is a great example for people that think that antibiotics are a conspiracy theory by pharmaceutical, or that pharma companies create things to get rich and perpetuate illness and stuff. Antibiotics are the absolute worst investment that any for profit business can ever make because you spend a ton of money discovering them and then the more that you validate it and the more that you use it, the less effective they become. It's the anti-blockbuster, which is, you spend a ton of money to discover it and then you want to have tons of years of use and sales of that product.

Raja Dhir: But the antibiotics get worse and worse with time, so people stop. The more successful your program is, the more you're borrowing sales. And so really, this is a combination of research initiatives, but also where public health needs to really step in and say, "Well, this is the point of subsidies. This is the point of research grants, is to align incentives, so that people can prioritize the discovery of it." So twofold, I think one, we need to use less and the way that we use less, is we educate people on what can and cannot benefit from antibiotics. The most recent statistic that I read on this said that about six to seven out of 10 courses of antibiotics are prescribed for a nonbacterial infection, six out of every 10 people, right?

Quinn: It's incredible, and this is why like, again, we are not medical doctors to be clear. But in talking with so many of them and the scientists behind the antibiotics, their good advice is just always like, if you are in... Look, doctors are amazing, I have plenty in my family, I'm so thankful for them. But it's almost like their experience with diet related training, which is just ask, "Will this antibiotic actually help the thing I am dealing with right now?" And just ask that question and the answer might totally be yes.

Raja Dhir: But they don't know. So here's the other side of the problem is-

Quinn: But my point is just like often, I mean, we're starting to get the data about how overprescribed this was at the beginning of COVID. And it's like, but it's a virus. And of course, you want to do whatever you can when you feel terrible or your life is danger, fully get it. But we've dug a hole, so I'm-

Raja Dhir: And again, these things go back to human behavior. There's an expectation of prescription when someone goes to their doctor because psychologically it feels like even if it's not going to help, the chance that it could, it's again, a precautionary principle. The doctor's going to say, "If I don't give it to you and I miss it, I'm in big trouble. If I do give it to you and you don't need it, it's a small cost." And so it's death by 1,000 paper cuts when it comes to resistance. It's really like the risk benefit calculus is stacked up to incentivize the prescription every time.

Quinn: Yeah, I don't know what the answer to this one is, but I'm going to keep trying to think about it and talking to people about it. It is a complicated one-

Raja Dhir: Well, believe it or not, the microbiome and educating people on the microbiome has really helped because now people start to visualize what that cost could be. If you start to think of this resident community inside of you, which is very beneficial, being challenged by antibiotics. And certainly since microbiome has become a little bit more mainstream, we've started to also ourselves, just notice a dramatic change in tune about the frivolous use on the patient side. And so again, I think that these things really help. But if we don't solve this problem, I mean it is a ticking time bomb. If we don't fix this by 2040 or 2050, we're going to have a ton of completely antibiotic resistant organisms. And we're already starting to see with Methicillin, which is kind of like our last-

Quinn: Right, that was our nuke option. It's crazy, and some of them truly, and this is not to minimize anything, but some of these diseases make COVID look like a cold. There's some scary shit out there. All right, Brian, take us into our action steps here, so we can get Raja out of here inside of a decent hour-

Brian: I mean, this is one of the biggest reasons we do this, is the action steps.

Quinn: Let's do it.

Brian: Yeah, let's get into what we can all do, what all of our listeners can do with specific action steps, to help support you and your mission, with their voice and their vote and their dollar. So let's start with their voice. What are big actionable, specific questions that all of us, Raja, could be asking of our government representatives to help support you in your mission?

Raja Dhir: So actually, I'll start with ecology and then we can move into the human side of things. So one of our really big projects in Seed Labs is, one of Seed Labs fellows discovered a bacteria found in the hindgut of the honeybee, which helps the honeybee to detoxify pesticides. And we've now run two honeybee field trials on this and published both of them in high impact journals and peer reviewed, as well as Probe The Mechanism. This technology or this 'probiotic for honeybees' is also an innovation, up for innovation of the year at Time Magazine and Fast Company's World Changing Ideas and so we're really passionate about our ecological division. And this is the first program that we've announced.

Raja Dhir: So the best way to support this, is to just familiarize yourself on the role that conventional and traditional agriculture and pesticide use and particularly neonicotinoid pesticides play in their contribution to honeybee colony collapse disorder. And with their voice, or their vote, or their advocacy at least champion the banning of neonicotinoid pesticides, their use or the rapid and fast adoption of some of these technologies, which can help to have this rescue effect. Because Europe has banned them, but the United States still to date has not. And all of our research suggests that these are the biggest drivers of death of American honeybees. So Apis mellifera is the species of organism. So from an ecological perspective, I would say that's something that we're really passionate about. The second from me-

Quinn: Awesome.

Raja Dhir: Yeah.

Quinn: Do you know any specific, sorry, any specific organizations that are working in an advocacy way on that issue? You can also send them to us after, if they're somebody you think is good-

Raja Dhir: Yeah, well, we have a big list which we can share with you, you can put it in the show notes afterwards.

Quinn: Awesome, that'd be great.

Raja Dhir: For sure and even more, I mean, I think just kind of this awareness that if we lose the honeybee, we're going to lose a lot of crops. I mean, the amount of crops that are, I was pretty blown away when I found out that almonds, actually, almond farmers have to rent honeybees seasonally to come and do their pollination because there's not enough-

Quinn: You can rent bees?

Raja Dhir: There's a burgeoning bee rental industry, which actually, I'm quite supportive of because it's a form of maintaining and keeping communities and stock of communities alive past the critical collapse if wild type bees might not be flourishing in a particular area. But yeah, there's an entire honeybee rental industry.

Brian: Would it be exploitive? Is that a word? Exploitive, to rent them out for just like pranks on friends?

Quinn: Brian, that's not [crosstalk 01:06:24], yeah.

Raja Dhir: I mean, I think that would perpetuate the myth that bees are dangerous. And so if I were you and wanted to prank your friends, I would just prank them and take them to an almond farm between February and August, then you can-

Brian: That does seem better, yeah.

Quinn: Perfect, perfect. I mean, sounds lovely, until it's not.

Raja Dhir: Yeah.

Quinn: Awesome, yeah. That's super great, yeah, if you could send us that list, that would be really helpful. We're always interested in-

Raja Dhir: And then in terms of our, we take a pretty big bet on education and we think that if you can make these issues that we work with less esoteric and more mainstream, that it'll have a huge ripple effect on either industries, but also which type of research gets funded versus which type of research does not? And so two more calls to action, the first is that we have a resource library on seed.com, where we cover everything, from the evolution of microbes from the beginning of time, to how your microbiome works, to the role of microbiome in diet. And we've kind of handpicked and selected a couple of publications which we think do a pretty good job of being integrist to the science and so that's always a call and where educated citizen or customer is kind of the best way to start.

Raja Dhir: And so that's the first place I would point everybody to, is if you want to just learn a little bit more about some of these topics in a deeper way, to just go and read and immerse yourself in this field. Uncover this stuff, we tried to break it down in a way that's also not too technical or too dense, but that also is a service to the basic science, rather than so far removed from the basic science, that is starts to sound like product marketing or anything like that. So that's the first one and then for women listeners, I would point them to your recently announced and launched women's health company, called LUCA Biologics. And it's just LUCA, L-U-C-A.bio.

Raja Dhir: And you can go there and read about the vaginal microbiome, you can learn about the role of microbes in women's health. I've done a lot of interviews with this, as well as our founding team for this company has, on how women's health is typically and historically underfunded and dismissed by both VC, but also by pharma because the market's not big enough, or it's non-life threatening, or they dismiss the symptoms, or you can't charge a premium for the treatments. I mean, whatever the indication might be. I think that it just kind of, it's a field that's worthy and deserving of world class science. And so you can learn a little bit more about what we're doing there.

Raja Dhir: Of course, it's going to be a couple of years before these technologies make their way through FDA trials. But it's a really good place to start and to at least start to separate fact from fiction in terms of those alternative medicines that are being presented as helping. And women that have recurrent infections are really desperate because there's no other alternative then these kind of antibiotics cycles. And so although there isn't anything today, starting to learn about ecology and risk factors and behavioral contributions can again, contribute to that education. I would like to keep it really simple, and just kind of let those be action items, so people can go do it.

Quinn: Awesome.

Brian: Hell yeah.

Quinn: No, we always appreciate simplicity. I appreciate you getting specific with that stuff. Awesome, so hey, Raja, last couple of questions and we'll get you out of here. Little more philosophical.

Brian: This has been awesome, by the way, I just want to say that.

Quinn: Yeah, thank you, thank you for all of your time and consideration.

Raja Dhir: I agree.

Quinn: I feel like we could just talk for hours and hours, which eventually people would just turn us off. But I'm happy to keep going at any point. Raja, when was the first time in your life when you realized you had the power of change or the power to do something meaningful?

Raja Dhir: Oh gosh, maybe it's not the first, but certainly yeah, I mean, I would probably say that it started very simple and actually quite young for me. My grandmother lives in a very small town at the base of the Himalayan mountains. And growing up, every other summer or so, I got the opportunity to go and before a lot of these areas became industrialized and developed, to just go spend time and observe how humans can coexist with animals or coexist with nature in a way that's not immediately self serving. And probably, I mean, in her own small way, it's wild stray dogs, and monkeys, and parrots. I mean, you name it, there's all kinds of animals which don't really have much food or don't starve.

Raja Dhir: And actually there's, in Northern India and India in general, food insecurity is a really big problem. And so I even remember at the ages of, as young as four or five years old, every morning I would go with my grandmother and before we ate breakfast, we would go feed those that were a little bit less fortunate. And again, it's not something on a very grand level, but just kind of this idea that what you can do in your individual life is and can be enough or at least is a great place to start.

Raja Dhir: I mean, you don't have to change the world to change the world so to speak. It's probably I would say the first thing that comes to mind. Is just the power of small actions that compound. And I'd go back and I'd see these same street dogs and monkeys, I'm telling you, it's a pretty dynamic ecosystem, or at least it was at that time. Every other year and so my takeaway from that would probably be don't beat yourself up, you don't have to invent clean energy to feel like you're making a contribution. Really simple moments of humanity can actually compound in a good way.

Quinn: I love that, man. Yeah, we've gotten some pretty touching things from people. And they usually are quite simple and it's nice because those things eventually snowball into bigger actions. Raja, who is someone in your life that's positively impacted your work in the past six months?

Raja Dhir: With that one I'm probably going to have to say, I mean, I can kick a rock at any member of our scientific advisory board and say that they're pretty pivotal to most of the researcher work that we do on a day-to-day basis. I'll probably pick the researcher at Caltech, the professor at Caltech that we're building this company with right now. Dr. Basmajian, who at least in the last six months I've been working quite closely with, in building this immuno-oncology microbial sciences company with.

Raja Dhir: It's kind of a radical idea about how we can leverage the microbiome to make cancer drugs work better. Though it's still kind of in the formative phases of getting off the ground. At least in the last six months I would say it's an area I've spent a significant period of time and been very fortunate to work with the best scientists in the world, in this area. And so I would probably say that or Dr. Ravel, who is my co-founder in our women's health company.

Quinn: Awesome, we believe in paying it forward. So appreciate that. It's always nice to get an unexpected shout out. Take us home, Brian.

Brian: Raja, what do you do when you feel overwhelmed?

Quinn: Self care.

Brian: What is your Raja time?

Raja Dhir: So I've really come to appreciate things that break the wheel, so to speak, of rumination. And so I think that being stressed or overwhelmed is a huge product of unresolved thoughts that are just continuing to percolate around without structure. And rather than just kind of force resolution artificially onto those thoughts, sometimes they need to kind of bask in that purgatory. I try to do things that just shut it off altogether, for as brief of a period of time as I can. And so I found things like mountain running, swimming in the ocean, even something as simple as just holding a plank until you collapse. Really simple things that just divert that monkey mind. At least temporarily, that do give you a bit of a reprieve from that rumination chamber if you will.

Raja Dhir: So, that's the type of thing that I like to do, is actually go in the opposite direction and just try to shut the whole thing down, altogether do like a hard reset for a short period of time, if you will. And another thing which is actually, given how pervasive technology is and how I grew up with literature, it even now sounds bizarre to say this. But picking up a hard copy of a book and not starting at the beginning, but just turning to some random page and just starting to read. I think most of the reason people don't read books any more, is because we put all this pressure on ourselves to finish what you started or do this, or do that.

Raja Dhir: And I think it's ridiculous, I think that just jump in, just get in there, vary it up, expose yourself constantly to new ideas. Make sure that your perspective is never out of focus, because you're too deep into one area, that you lose the larger picture. And just that type of spontaneous immersion as I call it, but I'm sure other people have called it that, or someone else might have called it something of this sort as well before, really helps. And then my last answer is like, it's a little bit of hard knocks, tough medicine if you will. But it's just, literally just stop thinking about yourself, just don't think about you or anything that you are doing and you can do that in simple ways.

Raja Dhir: By gardening or you can do that in more extreme ways, about like going and giving back and doing things of service to other people or other humanity. But damn, the amount of time people spend just self absorbed about themselves and their own tiny little life and their own future, it's just, it's ridiculous. Actually just stop thinking about yourself as the protagonist in the entire scheme of things that are happening in real time, around us. And whatever technique you need to use to do that, I think that really helps. And most of the time my stress just goes away quite quickly, when I do that.

Quinn: Yeah, I have found meditation to be extremely helpful in that respect, unless like stop being selfish and more just like, creating a disassociation between what is going on and taking it personally. And then that starts to apply itself to so many different things and we just need, we need more folks to hopefully, try to find a way of doing that. Whether it's not doing the doomscrolling and thinking it's affecting me, it all comes back to sort of the stoic philosophy of just like, look, affect what you can and you got to let go of everything else, for your own health and for everybody else's. We'll all be much more productive that way.

Raja Dhir: If you want to pull stoicism into it, just sleep on the floor for two nights and just see how all of a sudden you start to appreciate very simple stuff, or take cold showers. Literally very simple things that just break the wheel and give you a chance to start over again. I think the self help industry has made it seem that to be happy, you have to be Confucius and it's very simple, yeah.

Quinn: Awesome, Brian, last one.

Brian: Raja, we've got an awesome list of book recommendations from all of our past guests on Bookshop. So our question to everyone at the end of these, if you could send one book to Donald Trump, what book would it be?

Raja Dhir: Oh gosh, that's a... I mean, I would probably... Oh gosh, to Donald Trump. I mean, can he read? This is-

Brian: We're not sure, we think so.

Quinn: That's the standard clause that everybody asks. Imagine it's an Audible, an audio book, or someone reading to him, or it's just pictures. But yeah, basically what's your book to help somebody become a better human in 2020? Better human, better leader.

Raja Dhir: So I'm not going to answer the question of what I think he would read or if he would be able to benefit from it. I'll answer the question of, if I could impart anything into his mind, through a book, assuming that it absorbs and goes through. I'd probably send him something along the lines of The History of Western Civilization or Western Thought, like a good kind of a large scope history context book because America is a very young country and doesn't have a lot of its own history and culture. And I find that for people that really wrapped up in issues of the self, or the day-to-day ego, or posturing, or even kind of like dressing up self interest in the greater good, or population. I think that when you take a long view of things, it kind of helps sober you a little bit. So I would recommend anything from the history section of my bookshelf that tries to take a little bit of a longer view on the birth of civilization and-

Quinn: I love that.

Raja Dhir: Let's see what else.

Quinn: By the way, the very quick version of that is, The Lessons of History, you ever looked at that? It's super short because the couple, Durants, their other editions are like 15 volumes. But The Lessons of History will set you right very quickly. And it's like 100 pages or something amazing like that.

Raja Dhir: Yeah, so I would definitely go for something like that. And then I do want to also add probably a book on character. So there's a couple of things like that. But just to keep it focused, I'll go Deep Work by Cal Newport.

Quinn: One of my favorites.

Raja Dhir: Yeah, I think that, that would really help him out a little bit.

Quinn: Awesome, yeah. Deep Work is one of those, oh man, it's so good. You're just sitting there, reading, going, "I got to turn everything off, this is crazy." It's fantastic because if you ever have been in the space where you are accomplishing Deep Work, it is addicting and full-time, the flow as they call it. And setting yourself up for success, to find that is just hugely helpful, one of the best things you can do. Well Raja, this has been super helpful, man. Where can our listeners follow you online?

Raja Dhir: So, if you want to learn more about all things microbiome and about Seed, then just check our @Seed on Instagram. If you want to learn about my personal Instagram is just evolutionary biology. I post these pictures and explain deep scientific concepts and I try to do it simply. It's @wildraja. And yeah, I would say those are probably the two places to visually and intellectually go engage.

Quinn: Awesome, man. Well, thank you so much for your time and your deep and broad thinking on this stuff, and for trying to help fix us from the inside out. There's so much to learn, but it's really going to be a pretty amazing 10 years I think, I'm getting excited-

Raja Dhir: Yeah, I appreciate the questions and I also appreciate the mission you guys have. So hats off to you guys as well for bringing substance to the airwaves and talk soon.

Quinn: All right, awesome. All right, Raja. Take care, man.

Brian: Thanks so much, brother.

Raja Dhir: Thanks, guys.

Quinn: Thanks to our incredible guest today and thanks to all of you for tuning in. We hope this episode has made your commute, or awesome workout, or dish washing, or fucking dog walking late at night that much more pleasant. As a reminder, please subscribe to our free email newsletter at importantnotimportant.com. It has all the news most vital to our survival as a species.

Brian: And you can follow us all over the internet. You can find us on Twitter @Importantnotimp, just so weird. Also, on Facebook and Instagram @Importantnotimportant, Pinterest and Tumblr the same thing. So check us out, follow us, share us, like us, you know the deal. And please subscribe to our show wherever you listen to things like this. And if you're really fucking awesome, rate us on Apple Podcast. Keep the lights on, thanks.

Quinn: Please.

Brian: And you can find the show notes from today, right in your little podcast player and at our website, importantnotimportant.com.

Quinn: Thanks to the very awesome Tim Blane for our jamming music, to all of you for listening, and finally, most importantly, to our moms for making us. Have a great day.

Brian: Thanks, guys.

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